浠婂ぉ鏄細

瀹為獙瀹よ祫璁綉

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瀹為獙瀹よ祫璁綉鏃堕棿:2019-05-12 鐐瑰嚮: 娆?/span> 鐧惧害鎼滅储

銆愬璇汇€?/strong>01 鏂囩珷鑳屾櫙绠€浠?BACKGROUND INTRODUCTION 闅忕潃骞撮緞鐨勫闀匡紝浜虹被鐨勪竴涓樉钁楃殑鐢熺悊鍙樺寲灏辨槸琛€绠″唴鐨粏鑳烇紙ECs锛夋暟閲忓拰鍔熻兘鐨勪笅闄嶃€傛牴鎹绠¤“鑰佺悊璁猴紝琛€绠¤“閫€鏄“鑰佸拰鑰佸勾鎬х柧鐥呯殑涓昏鍘熷洜涔嬩竴銆傝櫧鐒舵瘺缁嗚绠℃暟閲忓拰鍔熻兘涓嬮檷涓ラ噸鍗卞浜虹被鍋ュ悍锛屼絾鍙戠敓杩欑鐜拌薄鐨勫師鍥犲嵈鑷充粖涓嶆槑銆傝繍鍔ㄦ槸淇冭繘鏂扮敓琛€绠″舰鎴?.....
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01

鏂囩珷鑳屾櫙绠€浠?/strong>

BACKGROUND INTRODUCTION

闅忕潃骞撮緞鐨勫闀匡紝浜虹被鐨勪竴涓樉钁楃殑鐢熺悊鍙樺寲灏辨槸琛€绠″唴鐨粏鑳烇紙ECs锛夋暟閲忓拰鍔熻兘鐨勪笅闄嶃€傛牴鎹绠¤“鑰佺悊璁猴紝琛€绠¤“閫€鏄“鑰佸拰鑰佸勾鎬х柧鐥呯殑涓昏鍘熷洜涔嬩竴銆傝櫧鐒舵瘺缁嗚绠℃暟閲忓拰鍔熻兘涓嬮檷涓ラ噸鍗卞浜虹被鍋ュ悍锛屼絾鍙戠敓杩欑鐜拌薄鐨勫師鍥犲嵈鑷充粖涓嶆槑銆傝繍鍔ㄦ槸淇冭繘鏂扮敓琛€绠″舰鎴愩€佸欢缂撹“鑰佺殑濂芥柟娉曪紝浣嗘槸闅忕潃骞撮緞鐨勫闀匡紝缁勭粐浼氬け鍘诲杩愬姩鐨勬晱鎰熸€э紝鑰岄€犳垚杩欎竴鐜拌薄鐨勫師鍥犺嚦浠婁篃骞朵笉娓呮銆?/p>

Sirtuin瀹舵棌鏄叺姣嶆煋鑹茶川娌夐粯淇″彿璋冭妭鍥犲瓙2锛坰ilent information regulator 2锛孲IRT2锛夌殑鍚屾簮鐗╋紝鏄竴绉嶄粠缁嗚弻鍒颁汉绫婚珮搴︿繚瀹堢殑NAD锛嬩緷璧栨€у幓涔欓叞鍖栭叾绫诲鏃忥紝璇ュ鏃忚繃琛ㄨ揪鏃跺彲浠ュ欢闀垮鍛姐€備汉绫籗irtuin瀹舵棌鐢?SIRT1锛峉IRT7鍏?涓垚鍛樼粍鎴愩€傚叾涓紝SIRT1鏄疭irtuin瀹舵棌涓渶鍙楀叧娉ㄧ殑涓€涓紝鏈変汉鐢氳嚦灏嗗叾绉颁负“闀垮鍩哄洜”銆傚湪骞磋交鑲岃倝涓紝SIRT1涓庣己琛€璇卞鐨勬柊鐢熻绠″舰鎴愩€佽绠℃澗寮涖€丒C琛拌€佹湁鍏炽€傜劧鑰岋紝鐩墠灏氫笉娓呮鍐呯毊缁嗚優SIRT1鑳藉惁鍙互璋冩帶楠ㄩ鑲岀粍缁囩殑寰绠¢噸鏋勩€傝嫢鍙互璋冭妭锛屽垯闅忓勾榫勫闀胯繃绋嬩腑鍐呯毊缁嗚優SIRT1鐨勫垎瑙g┒绔熸槸缁嗚優鑷富鐨勮繕鏄彲閫嗙殑锛熻縿浠婁篃骞朵笉娓呮銆?/p>

SIRT1婵€娲诲墏锛圫IRT1 activating compounds锛孲TACs锛夛紝濡傜櫧钘滆姦閱囧拰SRT1720宸茶瑙嗕负涓€绉嶆敼鍠勮“鑰佺浉鍏崇柧鐥呯殑娌荤枟鏂规硶銆備緥濡傦細閫氳繃浣跨敤鐑熼叞鑳烘牳鑻凤紙NR锛夋垨鐑熼叞鑳哄崟鏍歌嫹閰革紙NMN锛夌瓑NAD锛嬪墠浣撴潵鎭㈠NAD锛嬫按骞筹紝鍙彁楂楨Cs鐨勮绠$敓鎴愯兘鍔涳紝鎻愰珮骞奸紶鐨勮繍鍔ㄨ兘鍔涳紝闃叉涓庡勾榫勭浉鍏崇殑鐢熺悊琛伴€€銆備絾鍐呯毊缁嗚優涓璑AD锛嬪拰SIRT1娲绘€х殑闄嶄綆鏄惁浼氬鑷磋“鑰佽繃绋嬩腑寰绠$郴缁熺殑涓㈠け鍜岃“寮憋紝鐩墠骞朵笉娓呮銆?/p>

2018骞?鏈堬紝鏉ヨ嚜缇庡浗鍝堜經鍖诲闄㈢殑Das A绛変汉鑱斿悎楹荤渷鐞嗗伐瀛﹂櫌鍜屽澶曟硶灏间簹澶у浣╅浄灏旀浖鍖诲闄㈠湪銆奀ell銆嬫潅蹇楋紙IF锛?1锛?98锛岀敓鐗╀竴鍖?/strong>锛夊彂琛ㄤ簡棰樹负“Impairment of an Endothelial NAD锛嬶紞H2S Signaling Network Is a Reversible Cause of Vascular Aging”鐨勬枃绔犮€?/p>

02

鎵€鐢ㄥ埌鐨勪富瑕佹柟娉?/strong>

METHODS

1锛庡皬榧犺€愬姏璇曢獙锛氬湪鑰愬姏娴嬭瘯鍓嶏紝灏忛紶浠?0锛?5绫筹紡鍒嗛挓鐨勯€熷害璺?0鍒嗛挓锛屼互閫傚簲璺戞鏈?澶┿€傚湪浣庡己搴﹁€愬姏娴嬭瘯涓紝閫熷害浠? m锛弇in寮€濮嬶紝鎸佺画5 min锛岄€熷害姣忓垎閽熷鍔?娆★紝鐩村埌21 m锛弇in锛屼繚鎸佷笉鍙樸€傚湪楂樺己搴﹁€愬姏璇曢獙涓紝閫熷害浠?3 m锛弇in寮€濮嬶紝鍦?°鍊捐涓? min锛岄€熷害姣忓垎閽熷鍔?娆★紝鐩村埌20 m锛弇in锛屽苟淇濇寔20 min涓嶅彉銆傛瘡20鍒嗛挓锛岄€熷害澧炲姞5 m锛弇in锛屽苟淇濇寔20鍒嗛挓涓嶅彉銆傚湪涓ら」璇曢獙涓紝灏忛紶閮借杩愯鍒扮簿鐤插姏灏姐€傚綋鑰侀紶鍦ㄩ槻闇囨澘涓婂潗浜嗚秴杩?0绉掕€屾病鏈夎瘯鍥鹃噸鏂板紑濮嬭窇姝ユ椂锛屽氨琚涓烘槸绮剧柌鍔涘敖浜嗐€?/p>

2锛庡皬榧犺繍鍔ㄨ缁冿細鑰侀紶3澶╁墠寮€濮嬭窇姝ユ満绯荤粺鐨勮繍鍔ㄨ缁冭揪鍒?0绫筹紡鍒嗛挓锛?0鍒嗛挓銆傛垚鍔熷湴椹寲鐨勫姩鐗╋紝涔嬪悗鍦?°鍊捐璺戞鏈轰笅浠?5锛?20 m 锛?min閫熷害鎸佺画30鍒嗛挓锛?姣忓ぉ涓€娆¢敾鐐兼寔缁?0澶┿€傚湪鏁翠釜杩愬姩璁粌鏂规涓紝鎺ュ彈娌荤枟鐨勫皬榧犵粰浜圢MN 锛?00 mg锛弅g锛廳ay锛夊拰锛忔垨闃胯タ鏇垮凹 锛?0 mg锛弅g锛廳ay锛夈€傞€氳繃楗敤姘寸粰鑽殑NMN姣?澶╂洿鎹竴娆★紝閫氳繃椋熺墿缁欒嵂鐨勯樋瑗挎浛灏兼瘡澶╂洿鎹竴娆°€傚湪璁粌缁撴潫鏃跺灏忛紶杩涜浜嗗姏绔繍鍔ㄨ兘鍔涙祴璇曘€?/p>

3锛庢棆杞彴娴嬭瘯瀹為獙锛氳瘎浼拌繍鍔ㄥ崗璋冭兘鍔涳紝灏忛紶浠?杞紡鍒嗘亽閫熻浆2鍒嗛挓锛岃繘琛?娆″疄楠岋紝鍏辫3澶╀互閫傚簲鏃嬭浆銆傜4澶╋紝鍦ㄥ姞閫熻緤涓婁互440杞紡鍒嗚浆4鍒嗛挓锛岃繘琛?娆″疄楠岋紝璁板綍灏忛紶鍋滅暀鐨勬椂闂淬€?/p>

4锛庝笅鑲㈢己琛€妯″瀷鏋勫缓銆佸姣斿害澧炲己瓒呭0銆佸績鑴忚秴澹般€佸厜澹版垚鍍忓垎鏋愩€侀叾娲绘€у垎鏋愩€佸熀鍥犲垎鍨婸CR鍒嗘瀽銆佹祦寮忕粏鑳炴湳銆丷NA骞叉壈鍜岀梾姣掓劅鏌撱€佺粏鑳炶縼绉诲疄楠屻€佽绠″舰鎴愬疄楠屻€佷笁缁村煿鍏绘き鐞冪粏鑳炶縼绉诲疄楠屻€佷富鍔ㄨ剦鐡g幆璇曢獙銆佸垝鐥曞疄楠屻€佺粏鑳炲厤鐤崸鍏夈€丠锛咵鏌撹壊銆乄estern

03

鏂囩珷涓昏鍐呭鎽樿

ABSTRACT

闅忕潃骞撮緞澧為暱锛屾瘺缁嗚绠″瘑搴﹀拰琛€娴侀噺涓嬮檷鏄€犳垚浜虹敓鐥呭拰姝讳骸鐨勪富瑕佸師鍥犮€備簡瑙h繖绉嶇幇璞$殑鍙戠梾鏈哄埗灏嗘湁鍒╀簬浜虹被鍋ュ悍璋冭妭銆侼AD 锛嬪墠浣撻€氳繃婵€娲荤敤浜庤皟鑺傝繍鍔ㄥ拰楗闄愬埗锛圖R锛夌殑骞宠 ——鍘讳箼閰板寲閰秙irtuin锛圫IRT1锛?锛夋潵閫嗚浆琛拌€併€傜爺绌跺彂鐜板唴鐨粏鑳炰腑鐨凷IRT1鏄倢缁嗚優鍒嗘硨淇冭绠$敓鎴愪俊鍙风殑鍏抽敭浠嬭川銆傜敤NAD锛嬪墠浣撶儫閰拌兒鍗曟牳鑻烽吀NMN澶勭悊灏忛紶鍚庯紝NMN鍙績杩泂irt1渚濊禆閫斿緞锛屼粠鑰屽鍔犳瘺缁嗚绠″瘑搴︼紝浠ユ鎻愰珮鑰佸勾灏忛紶鐨勮娴侀噺鍜岃€愬姏锛岄敾鐐兼垨澧炲姞纭寲姘紙H2S锛夐兘鍙娇鍏舵晥鏋滃寮恒€傝繖浜涘彂鐜版湁鍒╀簬鏀瑰杽鍦ㄥ櫒瀹樺拰缁勭粐涓殑琛€娑叉祦鍔ㄣ€佹彁楂樹汉绫荤殑娲诲姩姘村钩骞堕噸寤鸿€佸勾浜虹敓鐞嗘椿鍔ㄧ殑鑹€у惊鐜€?/p>

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