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瞬时受体电位香草酸亚型1(TRPV1)在心肌缺血激活后可传导心绞痛信号,释放神经肽,减轻心肌梗死后的心肌细胞凋亡。目前,TRPV1激活抑制心肌梗死后细胞凋亡的具体机制尚不清楚。线粒体通透性转换孔(MPTP)的开放与心肌细胞缺血再灌注损伤密切相关,抑制其开放可保护心肌缺血后的心肌细胞抗凋亡。本研究证明,TRPV1激活通过抑制MPTP开放而减少心肌细胞凋亡。首先,本研究利用左冠状动脉前降支结扎术建立了TRPV1基因敲除(TRPV1-/-)和野生型(WT)小鼠心肌梗死模型,辅以环孢素A(CSA)预处理抑制MPTP开放,比较观察TRPV1、MPTP在心肌梗死中的作用。心肌组织切片氯化三苯基四氮唑(TTC)染色显示,心肌缺血24 h,TRPV1-/-小鼠的心肌梗死面积明显大于WT型小鼠。而经CSA预处理的TRPV1-/-小鼠比TRPV1-/-小鼠梗死面积明显减小。TUNEL检测心肌细胞凋亡指数(AI)揭示,WT型心肌梗死小鼠的AI明显低于TRPV1-/-心肌梗死小鼠,而CSA预处理明显降低TRPV1-/-小鼠心肌细胞的AI。Western印迹检测胱天蛋白酶3、胱天蛋白酶9、Bcl-2、Bax、p53和细胞色素C(Cyt-C)水平。结果证明,TRPV1的激活可抑制MPTP的开放,减少线粒体Cyt-C的外溢,降低胱天蛋白酶9和胱天蛋白酶3的表达。GENMEN光度法检测MPTP开放实验显示,激活的TRPV1明显抑制了MPTP的开放。本研究证实,急性心肌梗死后的TRPV1激活可能通过抑制MPTP开放而抵抗心肌细胞凋亡,对心肌起保护作用。
Transient receptor potential vanilloid subtype 1 (TRPV1) can induce angina pectoris after the activation of myocardial ischemia, release of neuropeptides, and alleviate cardiomyocyte apoptosis after myocardial infarction. At present, the specific mechanism of TRPV1 activation inhibiting apoptosis after myocardial infarction is not clear. The opening of mitochondrial permeability transition pore (MPTP) is closely related to myocardial ischemia-reperfusion injury, inhibition of its opening can protect myocardial cells from anti-apoptosis after myocardial ischemia. This study demonstrates that TRPV1 activation reduces cardiomyocyte apoptosis by inhibiting MPTP opening. First of all, in this study, TRPV1 knockout (TRPV1 - / -) and WT mice were established by anterior descending coronary artery ligation. Cyclosporine A (CSA) pretreatment inhibited MPTP Open to compare the role of TRPV1, MPTP in myocardial infarction. Myocardial tissue sections were stained with triphenyltetrazolium chloride (TTC). The area of myocardial infarction in TRPV1 - / - mice was significantly greater than that in WT mice at 24 h after myocardial ischemia. However, infarction area of TRPV1 - / - mice pretreated with CSA was significantly reduced than that of TRPV1 - / - mice. TUNEL detection of myocardial apoptosis index (AI) revealed that the AI of WT mice was significantly lower than that of TRPV1 - / - MI mice, while CSA pretreatment significantly reduced the AI of TRPV1 - / - mice. Western blotting was used to detect the levels of caspase 3, caspase 9, Bcl-2, Bax, p53 and cytochrome C (Cyt-C). The results demonstrate that TRPV1 activation can inhibit the opening of MPTP, reduce the mitochondrial Cyt-C spillover, reduce the expression of caspase 9 and caspase 3. GENMEN photometric detection of MPTP open experiments showed that activated TRPV1 significantly inhibited the opening of MPTP. This study confirmed that TRPV1 activation after acute myocardial infarction may be through the inhibition of MPTP opening and resistance to myocardial apoptosis, myocardial protection.