{"id":10812,"date":"2020-10-05T16:22:00","date_gmt":"2020-10-05T07:22:00","guid":{"rendered":"https:\/\/ebn2.arkray.co.jp\/english\/?page_id=10812"},"modified":"2020-11-25T17:19:35","modified_gmt":"2020-11-25T08:19:35","slug":"glycation-stress_12","status":"publish","type":"page","link":"https:\/\/ebn2.arkray.co.jp\/chinese\/academicinfo\/glycation-stress_12\/","title":{"rendered":"\u7cd6\u5316\u5e94\u6fc0\u4e0e\u963f\u5c14\u5179\u6d77\u9ed8\u75c7"},"content":{"rendered":"\n

\u7cd6\u5316\u5e94\u6fc0\u4e0e\u963f\u5c14\u5179\u6d77\u9ed8\u75c7<\/h2>\n\n\n

\u65e5\u672c\u540c\u5fd7\u793e\u5927\u5b66\u7814\u7a76\u751f\u9662 \u751f\u547d\u533b\u79d1\u5b66\u7814\u7a76\u79d1 \u7cd6\u5316\u5e94\u6fc0\u7814\u7a76\u4e2d\u5fc3
\u516b\u6728\u96c5\u4e4b \u6559\u6388 \u4e3b\u7f16<\/p>\n\n\n

\u75f4\u5446\u75c7\u4e0e\u963f\u5c14\u5179\u6d77\u9ed8\u75c7<\/h3>\n\n\n

2012\u5e74\u7684\u65e5\u672c\u75f4\u5446\u75c7\u8001\u5e74\u60a3\u8005\u4eba\u6570\u4f30\u8ba1\u4e3a462\u4e07\u4eba(1)<\/sup>\u3002\u6b64\u540e\u4ecd\u5728\u7ee7\u7eed\u589e\u957f\uff0c\u9884\u8ba1\u5c06\u57282025\u5e74\u8fbe\u5230675\u4e07\u4eba(\u60a3\u75c5\u738718.5%)\uff0c2050\u5e74\u8fbe\u5230797\u4e07\u4eba(\u60a3\u75c5\u738721.1%)\u3002\u7ecf\u8ba1\u7b97\uff0c\u52302025\u5e74\u65f6\uff0c65\u5c81\u53ca\u4ee5\u4e0a\u7684\u8001\u5e74\u4eba\u4e2d\u5927\u7ea6\u6bcf5\u4eba\u5c31\u67091\u4eba\u662f\u75f4\u5446\u75c7\u60a3\u8005\uff0c\u8fd9\u662f\u4e00\u79cd\u4efb\u4f55\u4eba\u90fd\u5f88\u6709\u53ef\u80fd\u7f79\u60a3\u7684\u75be\u75c5(\u5047\u8bbe\u5404\u5e74\u9f84\u6bb5\u7684\u75f4\u5446\u75c7\u60a3\u75c5\u7387\u81ea2012\u5e74\u4ee5\u6765\u4fdd\u6301\u4e0d\u53d8)\u3002<\/p>\n

\u75f4\u5446\u75c7\u662f\u6307\u66fe\u7ecf\u8fbe\u5230\u6b63\u5e38\u6c34\u5e73\u7684\u8ba4\u77e5\u529f\u80fd\uff0c\u56e0\u540e\u5929\u6027\u7684\u8111\u90e8\u75be\u75c5\u800c\u53d1\u751f\u6301\u7eed\u6027\u7684\u4e0b\u964d\uff0c\u5448\u73b0\u51fa\u5bf9\u65e5\u5e38\u751f\u6d3b\u548c\u793e\u4ea4\u751f\u6d3b\u9020\u6210\u5f71\u54cd\u7684\u72b6\u6001\uff0c\u662f\u4e00\u79cd\u5728\u6ca1\u6709\u610f\u8bc6\u969c\u788d\u7684\u60c5\u51b5\u4e0b\u5c31\u80fd\u89c2\u5bdf\u5230\u7684\u75c7\u72b6(2)<\/sup>\u3002\u4e16\u754c\u536b\u751f\u7ec4\u7ec7(WHO)\u7684\u56fd\u9645\u75be\u75c5\u5206\u7c7b\u7b2c10\u7248(ICD-10)\u4e2d\uff0c\u5c06\u5176\u5b9a\u4e49\u4e3a\u201c\u75f4\u5446\u662f\u7531\u4e8e\u8111\u90e8\u75be\u75c5\u9020\u6210\u7684\u75c7\u5019\u7fa4\uff0c\u901a\u5e38\u4e3a\u6162\u6027\u6216\u8fdb\u884c\u6027\u4e4b\u672c\u8d28\uff0c\u53ef\u9020\u6210\u591a\u79cd\u9ad8\u7ea7\u76ae\u8d28\u529f\u80fd\u4e4b\u969c\u788d\uff0c\u5305\u542b\u8bb0\u5fc6\u3001\u601d\u7ef4\u3001\u5b9a\u5411\u611f\u3001\u7406\u89e3\u80fd\u529b\u3001\u8ba1\u7b97\u3001\u5b66\u4e60\u80fd\u529b\u3001\u8bed\u8a00\u53ca\u5224\u65ad\u80fd\u529b\u201d(2)<\/sup>\u3002\u75f4\u5446\u75c7\u5206\u4e3a\u963f\u5c14\u5179\u6d77\u9ed8\u578b\u75f4\u5446\u75c7(\u963f\u5c14\u5179\u6d77\u9ed8\u75c7)(Alzheimer\u2019s disease\uff1aAD)\u3001\u8111\u8840\u7ba1\u6027\u75f4\u5446\u75c7(vascular dementia\uff1aVD)\u3001\u8def\u6613\u4f53\u75f4\u5446\u75c7(dementia with Lewy bodies\uff1aDLB)\u548c\u5176\u4ed6\u75be\u75c5\u5f15\u8d77\u7684\u75f4\u5446\u75c7\u8fd94\u79cd\u3002<\/p>\n

\u5728\u5c9b\u6839\u53bf\u6d77\u58eb\u753a\u8fdb\u884c\u7684\u8c03\u67e5\u53d1\u73b0\uff0c\u5728943\u540d65\u5c81\u53ca\u4ee5\u4e0a\u7684\u8001\u5e74\u4eba\u4e2d\uff0c\u6709104\u4eba\u88ab\u786e\u8ba4\u4e3a\u75f4\u5446\u75c7\u60a3\u8005\uff0c\u5176\u4e2dAD\u4e3a63.5%\uff0cVD\u4e3a15.4%\uff0cDLB\u4e3a4.8%\uff0c\u5e15\u91d1\u68ee\u75c5\u75f4\u5446(Parkinson\u2019s disease dementia\uff1aPDD)\u4e3a6.7%\uff0c\u8fdb\u884c\u6027\u6838\u4e0a\u6027\u9ebb\u75f9(progressive supranuclear palsy\uff1aPSP)\u4e3a1.9%\uff0c\u989d\u989e\u53f6\u53d8\u6027\u578b\u75f4\u5446\u75c7(frontotemporal lobar degeneration\uff1aFTLD)\u4e3a0.96%\uff0c\u7531AD\u76f4\u63a5\u5f15\u8d77\u7684\u75f4\u5446\u75c7\u5360\u523060%\u53ca\u4ee5\u4e0a(3)<\/sup>\u3002<\/p>\n

AD\u7684\u75c7\u72b6\u5305\u62ec\u201c\u8f7b\u5ea6\u8ba4\u77e5\u529f\u80fd\u969c\u788d\u201d(mild cognitive impairment\uff1aMCI)\u548c\u201c\u7cbe\u795e\u884c\u4e3a\u75c7\u72b6\u201d(\u5916\u56f4\u75c7\u72b6)(behavioral and psychological symptoms of dementia\uff1aBPSD)\u3002MCI\u7684\u75c7\u72b6\u6709\u8bb0\u5fc6\u969c\u788d\u3001\u89c6\u7a7a\u95f4\u969c\u788d\u3001\u5224\u65ad\u529b\u4e0b\u964d\u3001\u5931\u8bed\u3001\u5931\u7528\u3001\u5931\u8ba4\u7b49\uff0c\u8fd9\u4e9b\u75c7\u72b6\u7edf\u79f0\u4e3a\u6838\u5fc3\u75c7\u72b6(core symptom)\u3002BPSD\u5219\u5305\u62ec\u5174\u594b\u3001\u5c16\u53eb\u3001\u60c5\u7eea\u4e0d\u7a33\u3001\u7126\u8e81\u3001\u6e38\u8361\u3001\u6709\u6096\u793e\u4f1a\u6587\u5316\u7684\u4e0d\u5f53\u884c\u4e3a\u3001\u6027\u6b32\u8131\u6291\u5236\u3001\u6536\u96c6\u7656\u3001\u8c29\u9a82\u3001\u5c3e\u968f\u3001\u7126\u8651\u3001\u6291\u90c1\u3001\u5984\u60f3\u3001\u5e7b\u89c9\u7b49\u3002BPSD\u53c8\u53ef\u8fdb\u4e00\u6b65\u5206\u4e3a\u5174\u594b\u3001\u6613\u6fc0\u60f9\u3001\u7126\u8e81\u3001\u5e7b\u89c9\u3001\u5984\u60f3\u7b49\u9633\u6027\u75c7\u72b6(positive symptoms)\u548c\u4e4f\u529b\u3001\u6de1\u6f20\u3001\u6291\u90c1\u7b49\u9634\u6027\u75c7\u72b6(negative symptoms)\u3002\u53e6\u5916\uff0c\u7ea6\u670960%\uff5e90%\u7684\u75f4\u5446\u75c7\u60a3\u8005\u8868\u73b0\u51fa\u591a\u79cdBPSD\u75c7\u72b6\uff0c\u5176\u4e2d\u4ee5\u6de1\u6f20\u3001\u5174\u594b\u3001\u6613\u6fc0\u60f9\u3001\u6291\u90c1\u7b49\u6700\u4e3a\u5e38\u89c1(4)<\/sup>\u3002<\/p>\n

AD\u7684\u795e\u7ecf\u75c5\u7406\u5b66\u7279\u5f81\u4e3a\u5728\u8111\u5185\u6d77\u9a6c\u4f53(hippocampus)\u548c\u5927\u8111\u76ae\u5c42(cerebral cortex)\u4e2d\u53ef\u89c1\u840e\u7f29(atrophy)\uff0c\u5728\u663e\u5fae\u955c\u4e0b\u53ef\u5927\u8303\u56f4\u89c2\u5bdf\u5230\u795e\u7ecf\u7ec6\u80de\u7684\u8131\u843d\u3001\u8001\u5e74\u6591(senile plaques)\u548c\u795e\u7ecf\u539f\u7ea4\u7ef4\u7f20\u7ed3(neurofibrillary tangle\uff1aNFT)\u7684\u6c89\u79ef(\u56fe1)(5)<\/sup>\u3002NFT\u5728\u7535\u5b50\u663e\u5fae\u955c\u5f71\u50cf\u4e2d\u5448\u73b0\u4e3a\u4e00\u79cd\u7279\u6b8a\u7684\u7ea4\u7ef4\u675f\uff0c\u8be5\u7ea4\u7ef4\u675f\u88ab\u79f0\u4e3a\u914d\u5bf9\u87ba\u65cb\u6837\u7ea4\u7ef4(paired helical filament\uff1aPHF)\u3002\u8001\u5e74\u6591\u548cPHF\u7684\u4e3b\u8981\u6210\u5206\u88ab\u786e\u8ba4\u4e3a\u03b2-\u6dc0\u7c89\u6837\u86cb\u767d(amyloid-\u03b2 protein\uff1aA\u03b2)\u548c\u9ad8\u5ea6\u78f7\u9178\u5316\u7684tau\u86cb\u767d(tau protein)\u3002tau\u86cb\u767d\u5b58\u5728\u4e8e\u795e\u7ecf\u8f74\u7a81\u4e2d\uff0c\u662f\u4e00\u79cd\u5206\u5b50\u91cf\u7ea6\u4e3a5\u4e07\u7684\u5fae\u7ba1(microtubule)\u7ed3\u5408\u86cb\u767d\uff0c\u5176\u5177\u6709\u4fc3\u8fdb\u548c\u7a33\u5b9a\u5fae\u7ba1\u805a\u5408\u7684\u4f5c\u7528\u3002\u5fae\u7ba1\u6784\u6210\u7ec6\u80de\u9aa8\u67b6\uff0c\u5728\u7ec6\u80de\u5185\u7684\u86cb\u767d\u548c\u7ec6\u80de\u5185\u7ec6\u80de\u5668\u4e2d\u53d1\u6325\u7740\u8fd0\u8f93\u901a\u9053\u7684\u4f5c\u7528\u3002\u8fd9\u4e00\u7ec6\u80de\u5185\u8fd0\u8f93\u673a\u5236\u4f1a\u5728tau\u86cb\u767d\u78f7\u9178\u5316\u540e\uff0c\u56e0\u5fae\u7ba1\u5931\u7a33\u800c\u906d\u5230\u6291\u5236\u3002<\/p>\n

\"\"<\/p>\n

\u56fe<\/strong>1. <\/strong>\u963f\u5c14\u5179\u6d77\u9ed8\u75c7\u60a3\u8005\u8111\u5185\u7684\u8001\u5e74\u6591\u548c\u795e\u7ecf\u539f\u7ea4\u7ef4\u7f20\u7ed3<\/strong>(5)<\/sup>
<\/strong>plaques\uff1a\u8001\u5e74\u6591\uff0c tangles\uff1a\u795e\u7ecf\u539f\u7ea4\u7ef4\u7f20\u7ed3<\/h6>\n

\u53e6\u5916\uff0cA\u03b2\u6c89\u79ef\u5f62\u6210\u7684\u8001\u5e74\u6591,\u5bf9\u4e8eAD\u7684\u75be\u75c5\u7279\u5f02\u6027\u8981\u9ad8\u4e8eNFT\u3002\u5f25\u6f2b\u6027\u8001\u5e74\u6591(diffuse plaques)\u662fAD\u5927\u8111\u7684\u6700\u65e9\u671f\u75c5\u53d8\uff0c\u5176\u4e3b\u8981\u7531\u975e\u7ea4\u7ef4\u6027A\u03b2\u6c89\u79ef\u5f62\u6210\u3002\u5728\u8868\u73b0\u4e3a\u5e38\u67d3\u8272\u4f53\u663e\u6027\u9057\u4f20\u7684\u5bb6\u65cf\u6027AD\u4e2d\u53d1\u73b0\uff0cA\u03b2\u524d\u4f53(amyloid precursor protein\uff1aAPP)\u7684\u70b9\u7a81\u53d8(point mutation)\u548c\u91cd\u590d(duplication)\u4e0e\u8be5\u75be\u75c5\u76f8\u5173\u3002\u5728A\u03b2\u4e2d\uff0c\u805a\u5408\u7684A\u03b2\u5be1\u805a\u4f53(amyloid-\u03b2 aggregate)\u5c24\u5176\u5177\u6709\u795e\u7ecf\u6bd2\u6027\u3002\u7531\u6b64\u53ef\u63a8\u65ad\u51fa\uff0c\u5728AD\u7684\u53d1\u75c5\u673a\u7406\u4e2d\uff0cA\u03b2\u7684\u8111\u5185\u6c89\u79ef\u8981\u65e9\u4e8etau\u86cb\u767d\uff0c\u662f\u4e00\u79cd\u4e0eAD\u75c5\u56e0\u5bc6\u5207\u76f8\u5173\u7684\u73b0\u8c61\u3002\u56f4\u7ed5A\u03b2\u5c55\u5f00\u7684AD\u53d1\u75c5\u673a\u5236\u5b66\u8bf4\uff0c\u88ab\u79f0\u4e3a\u201c\u6dc0\u7c89\u6837\u86cb\u767d\u7ea7\u8054\u5047\u8bf4(amyloid cascade hypothesis)\u201d(6)<\/sup>\u3002<\/p>\n

\u53e6\u5916\uff0c\u4e0e\u6b63\u5e38\u5bf9\u7167\u7ec4\u76f8\u6bd4\uff0cAD\u60a3\u8005\u5927\u8111\u76ae\u5c42\u4e2d\u7684\u4e59\u9170\u80c6\u78b1\u8f6c\u79fb\u9176(choline acetyltransferase\uff1aChAT)\u6d3b\u6027\u4e0b\u964d\u3002AD\u75c5\u60a3\u8005\u5927\u8111\u76ae\u5c42\u7684ChAT\u6d3b\u6027\u4e0e\u603b\u4f53\u8ba4\u77e5\u8bc4\u4f30\u5206\u6570(global cognitive score)\u76f8\u5173\u3002\u5728AD\u7684\u57fa\u5e95\u524d\u8111(basal forebrain)\u7684Meynert\u57fa\u5e95\u6838(nucleus basalis of meynert\uff1aNBM)\u4e2d\uff0c\u80fd\u591f\u89c2\u5bdf\u5230\u80c6\u78b1\u80fd\u795e\u7ecf\u5143\u7684\u663e\u8457\u6027\u8131\u843d\uff0c\u4ece\u4f4d\u4e8e\u57fa\u5e95\u524d\u8111\u7684\u4e2d\u67a2\u795e\u7ecf\u7cfb\u7edf\u7ec6\u80de\u7fa4\u6295\u5c04(projection)\u81f3\u5927\u8111\u76ae\u5c42\u548c\u6d77\u9a6c\u4f53\u7684\u80c6\u78b1\u80fd\u795e\u7ecf\u901a\u8def\u51fa\u73b0\u7d0a\u4e71\u3002AChE\u6291\u5236\u5242\u548c\u5c3c\u53e4\u4e01(nicotine)\u80fd\u591f\u4fc3\u8fdb\u8111\u5185\u4e59\u9170\u80c6\u78b1\u7cfb\u7edf\u7684\u795e\u7ecf\u4f20\u5bfc\u3002\u4f46\u662f\uff0c\u7814\u7a76\u8bc1\u5b9e\uff0c\u5982\u679c\u4f7f\u7528\u963f\u6258\u54c1(atropine)\u548c\u4e1c\u83a8\u83ea\u78b1(scopolamine)\u6765\u963b\u65ad\u8111\u5185\u4e59\u9170\u80c6\u78b1\u7cfb\u7edf\u7684\u795e\u7ecf\u4f20\u5bfc\uff0c\u4f1a\u5bf9\u5b66\u4e60\u548c\u8bb0\u5fc6\u884c\u4e3a\u9020\u6210\u5f71\u54cd\u3002\u7531\u6b64\u53ef\u89c1\uff0c\u80c6\u78b1\u80fd\u795e\u7ecf\u969c\u788d\u4e0e\u5305\u62ec\u5b66\u4e60\u8bb0\u5fc6\u5728\u5185\u7684\u8ba4\u77e5\u529f\u80fd\u5bc6\u5207\u76f8\u5173\u3002\u8fd9\u79cd\u56e0\u80c6\u78b1\u751f\u6210\u4e0d\u8db3\u800c\u5f15\u53d1AD\u7684\u53d1\u75c5\u673a\u5236\u5b66\u8bf4\uff0c\u88ab\u79f0\u4e3a\u201c\u80c6\u78b1\u80fd\u5047\u8bf4(cholinergic hypothesis)\u201d(7)<\/sup>\u3002<\/p>\n

\u6b64\u5916\uff0c\u57fa\u4e8eAD\u60a3\u8005\u7684\u8001\u5e74\u6591\u6c89\u79ef\u4e0e\u795e\u7ecf\u7ec6\u80de\u8131\u843d\u5e76\u4e0d\u76f8\u5173\u8fd9\u4e00\u89c2\u5bdf\u7ed3\u679c\uff0c\u8fd8\u6709\u4e00\u79cd\u5b66\u8bf4\u8ba4\u4e3a\uff0c\u75f4\u5446\u75c7\u7684\u4e3b\u8981\u81f4\u75c5\u7269\u8d28\u662ftau\u86cb\u767d\uff0c\u4f5c\u4e3a\u5fae\u7ba1\u7a33\u5b9a\u56e0\u5b50\u7684tau\u86cb\u767d\u6d88\u5931\u540e\uff0c\u795e\u7ecf\u7ec6\u80de\u7684\u8f74\u7a81\u5904\u4fbf\u4f1a\u5f62\u6210\u914d\u5bf9\u87ba\u65cb\u6837\u7ea4\u7ef4(paired helical filament\uff1aPHF)\uff0c\u4ea7\u751fNFT\uff0c\u4ece\u800c\u5bfc\u81f4\u7ec6\u80de\u9aa8\u67b6\u7684\u53d8\u6027\u3002\u8fd9\u79cdAD\u53d1\u75c5\u673a\u5236\u5b66\u8bf4\u88ab\u79f0\u4e3a\u201ctau\u5047\u8bf4(tau hypothesis)\u201d(8-9)<\/sup>\u3002\u4e0d\u8fc7\uff0c\u5bf9\u4e8etau\u86cb\u767d\u7684\u8fc7\u5ea6\u78f7\u9178\u5316\u548cPHF\u7684\u5f62\u6210\uff0c\u54ea\u4e2a\u5148\u53d1\u751f\uff0c\u76ee\u524d\u5219\u4ecd\u5b58\u5728\u4e89\u8bae\u3002<\/p>\n

\u4ece\u86cb\u767d\u8d28\u53d8\u6027\u3001\u4ea4\u8054\u53cd\u5e94\u589e\u5f3a\u548cRAGE\u4ecb\u5bfc\u8bf1\u53d1\u708e\u75c7\u7684\u89c2\u70b9\u6765\u770b\uff0c\u7cd6\u5316\u4e3b\u8981\u4e0e\u6dc0\u7c89\u6837\u86cb\u767d\u7ea7\u8054\u5047\u8bf4\u548ctau\u5047\u8bf4\u6709\u5173\u3002<\/p>\n\n\n

\u963f\u5c14\u5179\u6d77\u9ed8\u75c7\u4e0e\u7cd6\u5c3f\u75c5<\/h3>\n\n\n

\u7cd6\u5c3f\u75c5\u7684\u5178\u578b\u5e76\u53d1\u75c7\u6709\u795e\u7ecf\u75be\u75c5(neuropathy)\u3001\u89c6\u7f51\u819c\u75c5\u53d8(retinopathy)\u3001\u80be\u75c5(nephropathy)\u3001\u5fc3\u8840\u7ba1\u75be\u75c5(cardiovascular disease)\u7b49\u3002\u6b64\u5916\uff0c\u5728\u7cd6\u5c3f\u75c5\u60a3\u8005\u4e2d\u75f4\u5446\u75c7\u53d1\u75c5\u7387\u8f83\u9ad8\uff0c\u8fd9\u4e00\u70b9\u4e5f\u5e7f\u4e3a\u4eba\u77e5(\u56fe2)(10)<\/sup>\u3002\u9e7f\u7279\u4e39\u5927\u5b66\u5728\u81ea1990\u5e74\u8d77\u7684\u4e24\u5e74\u95f4\uff0c\u5f00\u5c55\u4e86\u4e00\u9879\u5927\u89c4\u6a21\u6d41\u884c\u75c5\u5b66\u7814\u7a76(Rotterdam study)\uff0c\u9488\u5bf9\u5e73\u5747\u5e74\u9f84\u4e3a55\u5c81\u53ca\u4ee5\u4e0a\u76846370\u540d\u60a3\u8005(2\u578b\u7cd6\u5c3f\u75c5\u60a3\u8005(2DM)692\u540d\u3001\u975e\u7cd6\u5c3f\u75c5\u60a3\u80055678\u540d)\uff0c\u8c03\u67e5\u4e86\u7cd6\u5c3f\u75c5\u4e0e\u75f4\u5446\u75c7\u7684\u76f8\u5173\u6027(11)<\/sup>\u3002\u7ed3\u679c\u663e\u793a\uff0c\u6709126\u4eba(2.0%)\u53d1\u75c5\u75f4\u5446\u75c7\uff0c\u5176\u4e2d27.0%\u4e3a2DM\u3002\u8fd9126\u540d\u75f4\u5446\u75c7\u53d1\u75c5\u8005\u4e2d\uff0c\u670989\u4eba(70.6%)\u4e3aAD\uff1b\u672a\u53d1\u75c5\u75f4\u5446\u75c7\u76846244\u4eba\u4e2d10.5%\u4e3a2DM\u3002\u7531\u6b64\u7ed3\u679c\u63a8\u7b97\u51fa\u4e86\uff0c2DM\u4e0e\u975e\u7cd6\u5c3f\u75c5\u60a3\u8005\u76f8\u6bd4\uff0cAD\u53d1\u75c5\u98ce\u9669\u662f\u51761.9\u500d\u3002<\/p>\n

\"\"\u56fe<\/strong>2. <\/strong>\u7cd6\u5c3f\u75c5\u60a3\u8005\u548c\u5065\u5eb7\u4eba\u5728\u4e0d\u540c\u5e74\u9f84\u6bb5\u7684\u75f4\u5446\u75c7\u60a3\u75c5\u7387
<\/strong>\u25c6\uff1a\u7cd6\u5c3f\u75c5\u60a3\u8005\uff0c \u25a0\uff1a\u5065\u5eb7\u4eba<\/h6>\n

\u5bf9\u4e8e\u7cd6\u4ee3\u8c22\u80fd\u529b\u4e0e\u75f4\u5446\u75c7\u7684\u5173\u7cfb\uff0c\u66fe\u5728\u798f\u5188\u53bf\u4e45\u5c71\u753a\u8fdb\u884c\u8fc7\u4e00\u9879\u957f\u671f\u6027\u7684\u8c03\u67e5(12)<\/sup>\u3002\u57281988\u5e74\u81f32003\u5e74\u768415\u5e74\u95f4\uff0c\u5bf91017\u540d\u672a\u60a3\u75f4\u5446\u75c7\u7684\u5e74\u9f84\u4e3a60\u5c81\u53ca\u4ee5\u4e0a\u7684\u8001\u5e74\u4eba(\u5973\u6027580\u4eba\u3001\u7537\u6027487\u4eba)\u8fdb\u884c\u8ffd\u8e2a\u8c03\u67e5\uff0c\u5728\u8c03\u67e5\u5f00\u59cb\u65f6\uff0c\u5bf9232\u4eba(\u5973\u6027153\u4eba\u3001\u7537\u602779\u4eba)\u8fdb\u884c\u4e8675 g\u53e3\u670d\u8461\u8404\u7cd6\u8010\u91cf\u8bd5\u9a8c(oral glucose tolerance test\uff1aOGTT)\uff0c\u7528\u7531\u6b64\u5f97\u5230\u7684\u7cd6\u4ee3\u8c22\u80fd\u529b\u8bc4\u4ef7\u7ed3\u679c\uff0c\u7814\u7a76\u4e86\u8be5\u8bc4\u4ef7\u7ed3\u679c\u4e0e\u75f4\u5446\u75c7\u53d1\u75c5\u4e4b\u95f4\u7684\u5173\u7cfb\u3002\u7ed3\u679c\u663e\u793a\uff0c\u5173\u4e8e\u75f4\u5446\u75c7\u53d1\u75c5\u98ce\u9669(\u8c03\u6574\u6027\u522b\u548c\u5e74\u9f84\u540e)\uff0c\u82e5\u5c06\u7cd6\u8010\u91cf\u6b63\u5e38\u7ec4(control)\u4f5c\u4e3a1.0(n=115)\uff0c\u5219\u7a7a\u8179\u8840\u7cd6\u53d7\u635f\u7ec4(impaired fasting glycemia)\u4e3a0.63(n=13)\uff0c \u7cd6\u8010\u91cf\u51cf\u4f4e\u7ec4(impaired glucose tolerance)\u4e3a1.35(n=63)\uff0c\u7cd6\u5c3f\u75c5\u7ec4(diabetes)\u4e3a1.74(n=41)\uff0c\u4ea6\u5373\u7cd6\u4ee3\u8c22\u80fd\u529b\u8d8a\u4f4e\uff0c\u53d1\u75c5\u98ce\u9669\u8d8a\u9ad8\u3002\u7531\u6b64\u63a8\u6d4b\uff0c\u7cd6\u5c3f\u75c5\u548c\u7cd6\u4ee3\u8c22\u80fd\u529b\u4e0e\u75f4\u5446\u75c7\u53d1\u75c5\u76f8\u5173\u3002<\/p>\n

\u963f\u5c14\u5179\u6d77\u9ed8\u75c7\u4e0eAGEs<\/h3>\n

AD\u60a3\u8005\u5927\u8111\u7684\u795e\u7ecf\u75c5\u7406\u5b66\u7279\u5f81\u662f\u8111\u840e\u7f29\u3001\u8001\u5e74\u6591\u548c\u795e\u7ecf\u539f\u7ea4\u7ef4\u7f20\u7ed3\u3002\u8001\u5e74\u6591\u7531\u03b2-\u6dc0\u7c89\u6837\u86cb\u767d(amyloid-\u03b2 protein\uff1aA\u03b2)\u6784\u6210\uff0c\u662f\u4e00\u79cd\u5927\u7ea6\u753140\u4e2a\u6c28\u57fa\u9178\u7ec4\u6210\u7684\u80bd(A\u03b240\u3001A\u03b242)\uff0c\u5206\u5b50\u91cf\u4e3a4300\uff5e4500\u3002A\u03b2\u662f\u5728\u03b2-\u5206\u6ccc\u9176\u548c\u03b3-\u5206\u6ccc\u9176(secretase)\u4f5c\u7528\u4e0b\uff0c\u4ece\u6dc0\u7c89\u6837\u524d\u4f53\u86cb\u767d(amyloid-\u03b2 protein precursor\uff1aAPP)\u4e2d\u5206\u89e3\u51fa\u6765\u7684\u3002\u5728AD\u60a3\u8005\u4f53\u5185\uff0cA\u03b2\u4f1a\u51dd\u96c6\uff0c\u5e76\u5f62\u6210\u4e0d\u6eb6\u6027\u7ea4\u7ef4\uff0c\u4ee5\u6dc0\u7c89\u6837\u6c89\u79ef\u3002\u5728\u8461\u8404\u7cd6\u7684\u73af\u5883\u4e2d\u57f9\u517b\u540e\uff0cA\u03b2\u53d1\u751f\u7cd6\u5316\u548cAGE\u5316(AGE-A\u03b2)\u3002A\u03b2\u7684\u6c28\u57fa\u9178\u5e8f\u5217\u4e2d\uff0c\u7b2c16\u4f4d\u548c\u7b2c28\u4f4d\u6709\u8d56\u6c28\u9178\u6b8b\u57fa(Lys\uff1aK)\uff0c\u7b2c5\u4f4d\u6709\u7cbe\u6c28\u9178\u6b8b\u57fa(Arg\uff1aR)\uff0c\u8fd9\u4e9b\u6c28\u57fa\u9178\u5e8f\u5217\u4f4d\u70b9\u53ef\u80fd\u4e0e\u7cd6\u5316\u6709\u5173\u3002\u6b64\u5916\uff0c\u5728\u8461\u8404\u7cd6\u7684\u73af\u5883\u4e2d\u57f9\u517b\uff0cA\u03b2\u4f1a\u53d1\u751f\u51dd\u96c6\u3002\u4e0e\u672a\u6dfb\u52a0AGE-A\u03b2\u65f6\u76f8\u6bd4\uff0c\u5411A\u03b2-\u8461\u8404\u7cd6\u6eb6\u6db2\u4e2d\u6dfb\u52a0AGE-A\u03b2\u540e\uff0c\u51dd\u96c6\u88ab\u5927\u5927\u4fc3\u8fdb(13)<\/sup>\u3002\u7531\u6b64\u63a8\u6d4b\u51fa\uff0cAGE-A\u03b2\u53ef\u4ee5\u8d77\u5230\u4fc3\u8fdbA\u03b2\u51dd\u96c6\u7684\u201c\u79cd\u5b50(seed)\u201d\u4f5c\u7528\u3002\u6b64\u5916\uff0c\u5728\u989d\u53f6\u4e2d\u542b\u6709\u8001\u5e74\u6591\u7684\u7ec4\u7ec7\u7684\u86cb\u767d\u4e2d\u7684AGEs\u91cf\uff0cAD\u60a3\u8005\u8981\u6bd4\u5065\u5eb7\u8001\u5e74\u4eba\u9ad8\u51fa3\u500d(14)<\/sup>\u3002\u4f46\u662f\uff0c\u5728A\u03b2-\u8461\u8404\u7cd6\u53cd\u5e94\u7cfb\u7edf\u4e2d\u6dfb\u52a0\u7cd6\u5316\u53cd\u5e94\u6291\u5236\u5242\u6c28\u57fa\u80cd(aminoganidine)\u8fdb\u884c\u57f9\u517b\uff0c\u4f1a\u5bf9A\u03b2\u7684\u51dd\u805a\u5f62\u6210\u4ea7\u751f\u6291\u5236(15)<\/sup>\u3002\u53e6\u5916\uff0c\u73b0\u5df2\u8bc1\u5b9e\u8001\u4eba\u6591\u4e2d\u8fd8\u5b58\u5728\u620a\u7cd6\u7d20\u3001\u5421\u54af\u7d20\u548cCML(14-15)<\/sup>\u3002\u7531\u6b64\u63a8\u6d4b\uff0c\u56e0\u7cd6\u5316\u800c\u5f15\u8d77\u7684A\u03b2\u7684AGE\u5316\uff0c\u4e0e\u86cb\u767d\u4ea4\u8054\u7684\u5f62\u6210\u6709\u5173\uff0c\u662fA\u03b2\u51dd\u96c6\u7684\u4fc3\u8fdb\u56e0\u7d20\u4e4b\u4e00\u3002<\/p>\n

\u4eceAD\u60a3\u8005\u5927\u8111\u4e2d\u53d6\u5f97\u7684\u914d\u5bf9\u87ba\u65cb\u6837\u7ea4\u7ef4(paired helical filament\uff1aPHF)\u7684tau\u86cb\u767d\u5df2\u53d1\u751fAGE\u5316\u3002\u4f46\u662f\u4ece\u975eAD\u60a3\u8005\u6216\u6ca1\u6709\u60a3\u75f4\u5446\u75c7\u7684\u5927\u8111\u4e2d\u53d6\u5f97\u7684\u53ef\u6eb6\u6027tau\u86cb\u767d\u5e76\u672a\u89c2\u5bdf\u5230AGE\u5316\u7684\u8ff9\u8c61\u3002\u5728tau\u86cb\u767d\u7684in vitro\u5b9e\u9a8c\u7cfb\u7edf\u4e2d\uff0c\u53d1\u751f\u7cd6\u5316\u7684tau\u86cb\u767d\u5f62\u6210PHF\u6837\u7ea4\u7ef4\u3002\u800c\u6ca1\u6709\u53d1\u751f\u7cd6\u5316\u7684tau\u86cb\u767d\u4e0d\u4f1a\u5f62\u6210\u7ea4\u7ef4(16)<\/sup>\u3002PHF\u4e2d\u542b\u6709\u620a\u7cd6\u7d20\u3001\u5421\u54af\u7d20\u548cCML\u3002\u5e76\u4e14\uff0ctau\u86cb\u767d\u7684\u6c28\u57fa\u9178\u5e8f\u5217\u4e2d\u670913\u4e2a\u8d56\u6c28\u9178\u6b8b\u57fa\uff0c\u5176\u4e2d\u67096\u4e2a\u53d1\u751f\u4e86\u7cd6\u5316(17)<\/sup>\u3002tau\u86cb\u767d\u7684\u7cd6\u57fa\u5316\u4f4d\u70b9\u6b63\u662f\u5b83\u4e0e\u5fae\u7ba1\u7684\u7ed3\u5408\u4f4d\u70b9\uff0c\u56e0\u800c\u5bfc\u81f4\u7ed3\u5408\u529f\u80fd\u53d7\u635f\u3002\u7cd6\u5316tau\u86cb\u767d\u8bf1\u53d1\u6d3b\u6027\u6c27\u3001IL-6\u7b49\u7684\u6c27\u5316\u5e94\u6fc0\uff0c\u4f7f\u795e\u7ecf\u7ec6\u80de\u529f\u80fd\u53d7\u635f(18)<\/sup>\u3002\u7cd6\u5316tau\u86cb\u767d\u8bf1\u53d1\u6dc0\u7c89\u6837\u524d\u4f53\u86cb\u767d(amyloid-\u03b2 protein precursor\uff1aAPP)\u548cA\u03b2\u5f62\u6210\u3002tau\u86cb\u767d\u56e0\u78f7\u9178\u5316\u548c\u7cd6\u5316\u800c\u53d1\u751f\u5fae\u7ba1\u7ed3\u5408\u529f\u80fd\u4e0b\u964d\uff0c\u4f5c\u4e3atau\u86cb\u767d\u539f\u6709\u529f\u80fd\u7684\u7ec6\u80de\u5185\u4f20\u5bfc\u80fd\u529b\u964d\u4f4e\u3002\u56e0\u6b64\uff0c\u7ec6\u80de\u65e0\u6cd5\u5c06APP\u5206\u6ccc\u5230\u7ec6\u80de\u5916\uff0c\u7ec6\u80de\u5185APP\u84c4\u79ef\u3002\u901a\u8fc7\u4e0a\u8ff0\u673a\u5236\uff0cA\u03b2\u548ctau\u86cb\u767d\u7684\u7cd6\u5316\u4fc3\u8fdb\u4e86A\u03b2\u7684\u6c89\u79ef\u548c\u51dd\u96c6\uff0c\u540c\u65f6\u4e5f\u589e\u5f3a\u4e86tau\u86cb\u767d\u7684\u6c89\u79ef\u3002<\/p>\n

\u6b64\u5916\uff0cAD\u60a3\u8005\u5927\u8111\u5185\u7684\u5c0f\u80f6\u8d28\u7ec6\u80de(microglia)\u548c\u661f\u5f62\u80f6\u8d28\u7ec6\u80de(astrocyte)\u4e2d\u6240\u542b\u7684\u620a\u7cd6\u7d20\u3001CML\u4ee5\u53ca\u4f5c\u4e3aAGE\u53d7\u4f53\u7684RAGE(receptor for AGEs)(19)<\/sup>\uff0c\u4e0e\u5065\u5eb7\u8001\u5e74\u4eba\u76f8\u6bd4\u663e\u8457\u6027\u589e\u52a0\u3002\u5c0f\u80f6\u8d28\u7ec6\u80de\u662f\u4e00\u79cd\u5b58\u5728\u4e8e\u4e2d\u67a2\u795e\u7ecf\u7cfb\u7edf\u7684\u7ec6\u80de\uff0c\u53c8\u79f0\u5e38\u9a7b\u5de8\u566c\u7ec6\u80de(macrophage)\uff0c\u5177\u6709\u6e05\u9664\u548c\u4fee\u590d\u795e\u7ecf\u5143\u7b49\u7684\u529f\u80fd(20)<\/sup>\u3002\u53e6\u4e00\u65b9\u9762\uff0c\u5df2\u8bc1\u5b9e\u5c0f\u80f6\u8d28\u7ec6\u80de\u7684\u6fc0\u6d3b\u53ef\u5bfc\u81f4\u80bf\u7624\u574f\u6b7b\u56e0\u5b50(TNF-\u03b1)\u3001\u767d\u4ecb\u7d20(IL)-1\u03b2\u3001\u5e72\u6270\u7d20(IFN)\u7b49\u708e\u6027\u7ec6\u80de\u56e0\u5b50\u7684\u5f62\u6210\uff0c\u8868\u660e\u5b83\u53ef\u80fd\u5bf9\u795e\u7ecf\u7ec6\u80de\u5b58\u5728\u635f\u5bb3\u4f5c\u7528(21)<\/sup>\u3002\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u662f\u4e00\u79cd\u53ea\u5728\u8111\u548c\u810a\u9ad3\u4e2d\u5b58\u5728\u7684\u661f\u5f62\u795e\u7ecf\u80f6\u8d28\u7ec6\u80de\uff0c\u5728\u7ef4\u6301\u4e2d\u67a2\u795e\u7ecf\u7cfb\u7edf\u529f\u80fd\u65b9\u9762\u5177\u6709\u8c03\u8282\u8840\u6d41\u3001\u4e3a\u795e\u7ecf\u7ec6\u80de\u4f9b\u7ed9\u80fd\u91cf\u3001\u5e72\u9884\u7a81\u89e6\u529f\u80fd\u3001\u8c03\u8282\u795e\u7ecf\u9012\u8d28\u7b49\u4f5c\u7528(22)<\/sup>\u3002\u5411\u5c0f\u80f6\u8d28\u7684\u57f9\u517b\u7ec6\u80de\u4e2d\u6dfb\u52a0AGE\u5316\u9e21\u5375\u6e05\u86cb\u767d(chicken egg albumin-AGE)\u540e\uff0c\u53ef\u89c2\u5bdf\u5230RAGE\u4ecb\u5bfc\u7684NO(nitric oxide)\u3001IL-6\u3001TNF-\u03b1\u7b49\u7269\u8d28\u7684\u4ea7\u751f\uff0c\u5e76\u4f1a\u8bf1\u53d1\u708e\u75c7(23)<\/sup>\u3002\u53e6\u5916\uff0c\u5728\u5411\u5927\u9f20\u5927\u8111\u76ae\u5c42\u795e\u7ecf\u5143\u7ec6\u80de(cortical neuronal cell)\u57f9\u517b\u7cfb\u7edf\u6dfb\u52a0\u5404\u79cdAGEs\u7684\u5b9e\u9a8c\u4e2d\uff0c\u8bc1\u5b9e\u4e86\u4e0eAmadori \u5316\u5408\u7269(amadori products)\u3001\u4e59\u9187\u919b(glycolaldehyde)\u884d\u751f\u7684AGEs\u3001\u7532\u57fa\u4e59\u4e8c\u919b(methylglyoxal)\u884d\u751f\u7684AGEs\u3001\u4e59\u4e8c\u919b(glyoxal)\u884d\u751f\u7684AGEs\u76f8\u6bd4\uff0c\u7518\u6cb9\u919b(glyceraldehyde)\u884d\u751fAGEs\u5177\u6709\u66f4\u5f3a\u7684\u8bf1\u53d1\u51cb\u4ea1(apotosis)\u4f5c\u7528(24)<\/sup>\u3002\u6b64\u65f6\uff0cCML\u548cCEL\u5747\u672a\u8bf1\u53d1\u7ec6\u80de\u6b7b\u4ea1\u3002\u7531\u6b64\u63a8\u6d4b\u51fa\uff0c\u968f\u7740A\u03b2\u548c\u8001\u5e74\u6591\u5728\u5927\u8111\u5185\u7684\u4e0d\u65ad\u84c4\u79ef\u800c\u53d1\u751f\u7684AGEs\u751f\u6210\u548c\u84c4\u79ef\uff0c\u80fd\u591f\u8bf1\u5bfcA\u03b2\u51fa\u73b0\u795e\u7ecf\u6bd2\u6027\uff0c\u8bf1\u53d1RAGE\u4ecb\u5bfc\u7684\u708e\u75c7\u548c\u51cb\u4ea1\uff0c\u5e76\u53c2\u4e0eAD\u75c5\u60c5\u7684\u795e\u7ecf\u7ec6\u80de\u6b7b\u4ea1\u7684\u4fc3\u8fdb\u548c\u589e\u5f3a(\u56fe3)(25)<\/sup>\u3002<\/p>\n

\u4e0a\u8ff0\u5185\u5bb9\u8868\u660e\uff0c\u7075\u6d3b\u4f7f\u7528\u53ef\u51cf\u5c11\u7cd6\u5316\u6240\u5bfc\u81f4\u7684AGEs\u5f62\u6210\u53ca\u84c4\u79ef\u7684\u7269\u8d28\uff0c\u6216\u4f1a\u6210\u4e3a\u9632\u6b62AD\u53d1\u75c5\u7684\u6709\u6548\u63aa\u65bd(26-27)<\/sup>\u3002<\/p>\n

\"\"<\/p>\n

\u56fe<\/strong>3. AGEs<\/strong>\u5bf9\u963f\u5c14\u5179\u6d77\u9ed8\u75c7\u7684\u5f71\u54cd<\/strong>(25)<\/sup><\/strong><\/h6>\n
\n
References<\/span><\/h5>\n
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  1. \n
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    1. \u4e8c\u5bae\u5229\u6cbb\uff1a\u65e5\u672c\u306b\u304a\u3051\u308b\u8a8d\u77e5\u75c7\u306e\u9ad8\u9f62\u8005\u4eba\u53e3\u306e\u5c06\u6765\u63a8\u8a08\u306b\u95a2\u3059\u308b\u7814\u7a76\u7dcf\u62ec\u7814\u7a76\u5831\u544a\u66f8, \u539a\u751f\u52b4\u50cd\u7701; 2015.<\/li>\n
    2. \u8a8d\u77e5\u75c7\u75be\u60a3\u6cbb\u7642\u30ac\u30a4\u30c9\u30e9\u30a4\u30f32010 ; \u65e5\u672c\u795e\u7d4c\u5b66\u4f1a\u76e3\u4fee.<\/li>\n
    3. Wada-Isoe K, et al.<\/i>\uff1aNeuroepidemiology. 2009; 32: 101\u2013106.<\/li>\n
    4. Ileda M et al.<\/i>\uff1aJ Neurol Neurosurg Psychiatry. 2004; 75: 146\u2013148.<\/li>\n
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    7. Francis PT, et al.<\/i>\uff1aJ Neurol Neurosurg Psychiatry. 1999; 66: 137\u2013147.<\/li>\n
    8. Mudher A, et al.<\/i>\uff1aTrends Neurosci. 2002 ; 25(1): 22-26.<\/li>\n
    9. Maccioni RB, et al.<\/i>\uff1aArchives of Medical Research. 41; 2010: 226-231.<\/li>\n
    10. Kimura R, et al.<\/i>\uff1aPsychogeriatrics. 2008; 8: 73-78.<\/li>\n
    11. Ott A, et al.<\/i>\uff1aNeurology 53(9); 1999: 1937-1942.<\/li>\n
    12. Ohara T, et al.<\/i>\uff1aNeurology. 2011; 77: 1126\u20131134.<\/li>\n
    13. Vitek MP, et al.<\/i>\uff1aProc Natl Acad Sci USA. 1994; 91: 1994.<\/li>\n
    14. Smith MA, et al.<\/i>\uff1aProc Natl Acad Sci USA. 1994; 91: 5710-5714.<\/li>\n
    15. Horie K, et al.<\/i>\uff1aBiochem Biophys Res Commun, 1997; 236: 327\u2013332. 1997<\/li>\n
    16. Ledesma MD, et al.<\/i>\uff1aJ Biol Chem. 1994; 269: 21614-21619.<\/li>\n
    17. Nacharaju P, et al.<\/i>\uff1aJ Neurochem. 1997; 69: 1709-1719.<\/li>\n
    18. Yan SD, et al.<\/i>\uff1aProc. Nati. Acad. Sci. USA: 1994: 7787-7791<\/li>\n
    19. Srikanth V, et al.<\/i>\uff1aNeurobiology of Aging. 2011; 32: 763\u2013777.<\/li>\n
    20. Takeda A, et al.<\/i>\uff1aActa Neuropathol. 1998; 95: 555\u2013558.<\/li>\n
    21. \u932b\u6751\u660e\u751f\uff1a\u798f\u5ca1\u533b\u8a8c. 100; 243-247 2009<\/li>\n
    22. Hamby ME, et al.<\/i>\uff1aNeurotherapeutics. 2010; 7: 494-506.<\/li>\n
    23. Dukic-Stefanovic S, et al.<\/i>\uff1aJournal of Neurochemistry. 2003; 87: 44\u201355.<\/li>\n
    24. Takeuchi M, et al.<\/i>\uff1aJ. Neuropathol. Exp. Neurol. 2000; 59: 1094\u20131105.<\/li>\n
    25. \u4f50\u3005\u6728\u4fe1\u5e78\uff1aAGEs\u3068\u30a2\u30eb\u30c4\u30cf\u30a4\u30de\u30fc\u75c5, AGEs\u306e\u7814\u7a76\u306e\u6700\u524d\u7dda. 2004: 171-177.<\/li>\n
    26. Dukic-Stefanovic C, et al.<\/i>\uff1aBiogerontology. 2001; 2: 19\u201334.<\/li>\n
    27. Munch G, et al.<\/i>\uff1aBiochem Soc Trans. 2003; Pt 6: 1397-1399.<\/li>\n<\/ol>\n<\/li>\n<\/ol>\n<\/div>\n\n\n
      \n\n\n\n
      \u7cd6\u5316\u5e94\u6fc0\u548c\u6297\u8870\u8001<\/strong><\/h5>\n\n\n\n