AbMole科研小講堂丨Metformin：在代謝、腫瘤、衰老與神經(jīng)疾病動物模型中的多面作用Metformin（1,1-Dimethylbiguanide，AbMole，M3244）是一種具有廣泛研究價值的化合物，其核心作用機制涉及能量代謝的調(diào)控與多靶點信號通路的干預(yù)。研究表明，Metformin（二甲雙胍，AbMole，M2049）可通過抑制線粒體復(fù)合物I，減少ATP生成并改善胰島素敏感性。在能量代謝研究中，Metformin（CASNo.：1115-70-4）通過提高細(xì)胞內(nèi)AMP/ATP比值，變構(gòu)激活A(yù)MP依賴的蛋白激酶（AMPK），進而調(diào)控下游糖脂代謝相關(guān)基因的表達(dá)ADDINEN.CITE<EndNote><Cite><Author>Bailey</Author><Year>2017</Year><RecNum>1491</RecNum><DisplayText><styleface="superscript">1</style></DisplayText><record><rec-number>1491</rec-number><foreign-keys><keyapp="EN"db-id="f2td9w00a22awteprfrp9vaup9d9zwa9tdfr"timestamp="1764639297">1491</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Bailey,CliffordJ%JDiabetologia</author></authors></contributors><titles><title>Metformin:historicaloverview</title></titles><pages>1566-1576</pages><volume>60</volume><number>9</number><dates><year>2017</year></dates><isbn>0012-186X</isbn><urls></urls></record></Cite><Cite><Author>Kirpichnikov</Author><Year>2002</Year><RecNum>1492</RecNum><record><rec-number>1492</rec-number><foreign-keys><keyapp="EN"db-id="f2td9w00a22awteprfrp9vaup9d9zwa9tdfr"timestamp="1764639318">1492</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Kirpichnikov,Dmitri</author><author>McFarlane,SamyI</author><author>Sowers,JamesR%JAnnalsofinternalmedicine</author></authors></contributors><titles><title>Metformin:anupdate</title></titles><pages>25-33</pages><volume>137</volume><number>1</number><dates><year>2002</year></dates><isbn>0003-4819</isbn><urls></urls></record></Cite></EndNote>1。Metformin在動物疾病模型的研究中具有廣泛的應(yīng)用，包括腫瘤、肝病、肥胖、心血管疾病、年齡相關(guān)疾病、腎臟疾病、糖尿病等多種動物模型。Metformin（二甲雙胍，AbMole，M2049）通過多種不同的分子機制，在上述一系列疾病模型中發(fā)揮作用。例如在細(xì)胞和動物的研究中發(fā)現(xiàn)，二甲雙胍抑制了AMPK依賴途徑或獨立途徑中糖生成基因的表達(dá)，從而抑制肝臟葡萄糖的產(chǎn)生。此外，二甲雙胍還可通過限制乳酸的生物利用增強葡萄糖的運輸和吸收，或改變腸道微生物群，降低小鼠的血糖水平。Metformin還可用于抑制腫瘤細(xì)胞的生長、存活和轉(zhuǎn)移，同時改變腫瘤微環(huán)境以抑制癌癥的發(fā)展，其分子機制包括抑制mTOR信號、p53激活、自噬和誘導(dǎo)凋亡、ROS生成、DNA損傷和改善腫瘤的免疫微環(huán)境ADDINEN.CITE<EndNote><Cite><Author>Wu</Author><Year>2022</Year><RecNum>1495</RecNum><DisplayText><styleface="superscript">2,3</style></DisplayText><record><rec-number>1495</rec-number><foreign-keys><keyapp="EN"db-id="f2td9w00a22awteprfrp9vaup9d9zwa9tdfr"timestamp="1764640433">1495</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Wu,Zihong</author><author>Zhang,Caidie</author><author>Najafi,Masoud%JJournalofcellcommunication</author><author>signaling</author></authors></contributors><titles><title>Targetingofthetumorimmunemicroenvironmentbymetformin</title></titles><pages>333-348</pages><volume>16</volume><number>3</number><dates><year>2022</year></dates><isbn>1873-9601</isbn><urls></urls></record></Cite><Cite><Author>Lv</Author><Year>2020</Year><RecNum>1494</RecNum><record><rec-number>1494</rec-number><foreign-keys><keyapp="EN"db-id="f2td9w00a22awteprfrp9vaup9d9zwa9tdfr"timestamp="1764640379">1494</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Lv,Ziquan</author><author>Guo,Yajie</author></authors></contributors><titles><title>MetforminandItsBenefitsforVariousDiseases</title><short-title>Metformin’sbenefitsondiseases</short-title></titles><volume>Volume11-2020</volume><keywords><keyword>Metformin,Benefits,Diseases,MitochondrialrespiratorychaincomplexI,AMPK</keyword></keywords><dates><year>2020</year><pub-dates><date>2020-April-16</date></pub-dates></dates><isbn>1664-2392</isbn><work-type>Review</work-type><urls><related-urls><url>/journals/endocrinology/articles/10.3389/fendo.2020.00191</url></related-urls></urls><electronic-resource-num>10.3389/fendo.2020.00191</electronic-resource-num><language>English</language></record></Cite></EndNote>2,3。Metformin（二甲雙胍，AbMole，M2049）在衰老的小鼠和線蟲模型中，還能夠降低ROS、減少DNA損傷、抑制炎癥反應(yīng)和細(xì)胞自噬ADDINEN.CITE<EndNote><Cite><Author>Barzilai</Author><Year>2016</Year><RecNum>1496</RecNum><DisplayText><styleface="superscript">4</style></DisplayText><record><rec-number>1496</rec-number><foreign-keys><keyapp="EN"db-id="f2td9w00a22awteprfrp9vaup9d9zwa9tdfr"timestamp="1764640600">1496</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Barzilai,Nir</author><author>Crandall,JillP</author><author>Kritchevsky,StephenB</author><author>Espeland,MarkA%JCellmetabolism</author></authors></contributors><titles><title>Metforminasatooltotargetaging</title></titles><pages>1060-1065</pages><volume>23</volume><number>6</number><dates><year>2016</year></dates><isbn>1550-4131</isbn><urls></urls></record></Cite></EndNote>4。在神經(jīng)科學(xué)研究中，Metformin在APP/PS1轉(zhuǎn)基因阿爾茨海默癥模型小鼠中被用于評估其對腦能量代謝和海馬神經(jīng)元突觸可塑性的潛在影響，結(jié)果證實Metformin改善了小鼠的淀粉樣斑塊的沉積和小鼠的記憶障礙ADDINEN.CITE<EndNote><Cite><Author>Ou</Author><Year>2018</Year><RecNum>1493</RecNum><DisplayText><styleface="superscript">5</style></DisplayText><record><rec-number>1493</rec-number><foreign-keys><keyapp="EN"db-id="f2td9w00a22awteprfrp9vaup9d9zwa9tdfr"timestamp="1764640281">1493</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Ou,Zhenri</author><author>Kong,Xuejian</author><author>Sun,Xiangdong</author><author>He,Xiaosong</author><author>Zhang,Le</author><author>Gong,Zhuo</author><author>Huang,Jingyi</author><author>Xu,Biao</author><author>Long,Dahong</author><author>Li,Jianhua%JBrain,behavior,</author><author>immunity</author></authors></contributors><titles><title>MetformintreatmentpreventsamyloidplaquedepositionandmemoryimpairmentinAPP/PS1mice</title></titles><pages>351-363</pages><volume>69</volume><dates><year>2018</year></dates><isbn>0889-1591</isbn><urls></urls></record></Cite></EndNote>5。Metformin在多種動物疾病模型中的應(yīng)用及其作用機制ADDINEN.CITE<EndNote><Cite><Author>Lv</Author><Year>2020</Year><RecNum>1494</RecNum><DisplayText><styleface="superscript">3</style></DisplayText><record><rec-number>1494</rec-number><foreign-keys><keyapp="EN"db-id="f2td9w00a22awteprfrp9vaup9d9zwa9tdfr"timestamp="1764640379">1494</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Lv,Ziquan</author><author>Guo,Yajie</author></authors></contributors><titles><title>MetforminandItsBenefitsforVariousDiseases</title><short-title>Metformin’sbenefitsondiseases</short-title></titles><volume>Volume11-2020</volume><keywords><keyword>Metformin,Benefits,Diseases,MitochondrialrespiratorychaincomplexI,AMPK</keyword></keywords><dates><year>2020</year><pub-dates><date>2020-April-16</date></pub-dates></dates><isbn>1664-2392</isbn><work-type>Review</work-type><urls><related-urls><url>/journals/endocrinology/articles/10.3389/fendo.2020.00191</url></related-urls></urls><electronic-resource-num>10.3389/fendo.2020.00191</electronic-resource-num><language>English</language></record></Cite></EndNote>3范例詳解Metabolism.2023Mar;140:155398.中國科技大學(xué)的研究團隊在上述論文中使用了AbMole的Metformin（二甲雙胍;1,1-Dimethylbiguanide，M3244），探究了間充質(zhì)干細(xì)胞（MSCs）聯(lián)合纖維蛋白支架（MSCs/FG）與Metformin在糖尿病傷口愈合中的作用及機制，發(fā)現(xiàn)二者協(xié)同通過Akt/mTOR通路促進VEGF介導(dǎo)的血管生成，且Metformin呈現(xiàn)劑量依賴性效應(yīng)ADDINEN.CITEADDINEN.CITE.DATA6。Thedose-dependenteffectsofmetformin(MTF)ontheAkt/mTORactivationandmigrationinfibroblastsandkeratinocytesADDINEN.CITEADDINEN.CITE.DATA6.AbMole是ChemBridge中國區(qū)官方指定合作伙伴。*本文所述產(chǎn)品僅供科研使用參考文獻(xiàn)及鳴謝ADDINEN.REFLIST(1)Bailey,C.J.J.D.Metformin:historicaloverview.2017,60(9),1566-1576.Kirpichnikov,D.;McFarlane,S.I.;Sowers,J.R.J.A.o.i.m.Metformin:anupdate.2002,137(1),25-33.(2)Wu,Z.;Zhang,C.;Najafi,M.J.J.o.c.c.;signaling.Targetingofthetumorimmunemicroenvironmentbymetformin.2022,16(3),333-3