發(fā)布時(shí)間：2018-03-17 21:34

  本文選題：瞬時(shí)受體電位香草酸亞型1　切入點(diǎn)：凋亡　出處：《重慶醫(yī)科大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：背景:在心肌缺血時(shí),瞬時(shí)受體電位香草酸亞型1(transient receptor potential vanilloid1,TRPV1)被激活,通過傳導(dǎo)心絞痛信號(hào)和釋放神經(jīng)肽,從而減輕心肌梗死后心肌細(xì)胞凋亡。目前,TRPV1抑制心肌梗死后凋亡作用的具體機(jī)制尚不清楚。近年來的研究表明,線粒體通透性轉(zhuǎn)換孔(Mitochondrial permeability transitionpore,MPTP)的開放與心肌細(xì)胞缺血再灌注損傷密切相關(guān),抑制其開放可減輕心肌缺血后心肌細(xì)胞凋亡。目的:探討瞬時(shí)受體電位香草酸亞型1激活是否通過抑制線粒體通透性轉(zhuǎn)換孔開放抑制小鼠心肌梗死后細(xì)胞凋亡。方法:首先,本研究利用左冠狀動(dòng)脈前降支結(jié)扎術(shù)建立了野生型(WT)和TRPV1基因敲除(TRPV1-/-)兩種小鼠的心肌梗死模型,輔以環(huán)孢素A(CSA)預(yù)處理抑制MPTP開放,比較觀察TRPV1、MPTP在心肌梗死中的作用。分別進(jìn)行心肌損傷測(cè)定及線粒體通透性轉(zhuǎn)換孔開放性測(cè)定。結(jié)果:本研究證明,TRPV1激活通過抑制MPTP開放而減少心肌細(xì)胞凋亡。心肌組織切片氯化三苯基四氮唑(TTC)染色顯示,心肌缺血24 h后,TRPV1-/-小鼠的心肌梗死面積明顯大于WT型小鼠,而經(jīng)CSA預(yù)處理的TRPV1-/-小鼠比TRPV1-/-小鼠梗死面積明顯減小。TUNEL檢測(cè)心肌細(xì)胞凋亡指數(shù)(AI)揭示,WT型心肌梗死小鼠的AI明顯低于TRPV1-/-心肌梗死小鼠,而CSA預(yù)處理明顯降低TRPV1-/-小鼠心肌細(xì)胞的AI。Western印跡檢測(cè)胱天蛋白酶3(caspase 3)、胱天蛋白酶9(caspase 9)、p53、Bcl-2/Bax比值和細(xì)胞色素C(Cyt-C)水平。結(jié)果證明,TRPV1的激活可抑制MPTP的開放,減少線粒體Cyt-C的外溢,降低caspase 9和caspase 3的表達(dá)。GENMEN光度法檢測(cè)MPTP開放實(shí)驗(yàn)顯示,激活的TRPV1明顯抑制MPTP的開放。本研究證實(shí),急性心肌梗死后的TRPV1激活可能通過抑制MPTP開放而抵抗心肌細(xì)胞凋亡,對(duì)心肌起保護(hù)作用。
[Abstract]:Background: transient receptor potential vanilloid1 TRPV1 (transient receptor potential) is activated during myocardial ischemia by signaling angina pectoris and releasing neuropeptides. At present, the mechanism of TRPV1 inhibiting apoptosis after myocardial infarction is not clear. Recent studies have shown that TRPV1 inhibits apoptosis after myocardial infarction. The opening of mitochondrial permeability transition pore Mitochondrial permeability transitionporedo (MPTP) was closely related to myocardial ischemia-reperfusion injury. To investigate whether the activation of transient receptor potential vanilic acid subtype 1 can inhibit myocardial apoptosis after myocardial ischemia by inhibiting mitochondrial permeability transition pore. Methods: firstly, we investigated whether the activation of vanillic acid subtype 1 could inhibit apoptosis after myocardial infarction in mice. In this study, two kinds of myocardial infarction models were established by left coronary artery anterior descending coronary artery ligation (WTW) and TRPV1 gene knockout TRPV1 / -) mice, which were pretreated with cyclosporine (CSA) to inhibit the opening of MPTP. The role of TRPV1 MPTP in myocardial infarction was compared. Myocardial injury and opening of mitochondrial permeability transition pore were measured respectively. Results: this study demonstrated that TRPV1 activation can reduce cardiomyocyte apoptosis by inhibiting the opening of MPTP. The muscle tissue sections were stained with TTCChloride-triphenyl tetrazolium chloride. After 24 hours of myocardial ischemia, the myocardial infarction size of TRPV1-r-mice was significantly larger than that of WT mice. However, the infarct size of TRPV1-r-mice pretreated with CSA was significantly smaller than that of TRPV1-r-mice. Tunel showed that the AI of mice with WT-type myocardial infarction was significantly lower than that of mice with TRPV1-r- myocardial infarction. CSA pretreatment significantly decreased the levels of cystatin 3, caspase 3, cystatin 9, p53, Bcl-2 / Bax and cytochrome Cyt-Con in TRPV1-r-mouse cardiomyocytes. The results showed that the activation of TRPV1 could inhibit the opening of MPTP and reduce the spillover of mitochondrial Cyt-C. Inhibition of expression of caspase 9 and caspase 3 by MPTP opening assay showed that activated TRPV1 significantly inhibited the opening of MPTP. This study confirmed that TRPV1 activation after acute myocardial infarction may resist cardiomyocyte apoptosis by inhibiting MPTP opening. Protect the myocardium.
【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R542.22

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本文編號(hào)：1626581