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瞬时受体电位香草酸亚型1(transient receptor potential vanilloid 1,TRPV1)在心肌缺血激活后可传导心绞痛信号和释放P物质(substance P,SP).SP是速激肽家族成员之一,主要通过结合并激活神经激肽1(neurokinin 1,NK1)受体发挥作用.TRPV1和SP在缺血性心脏病中对心功能的恢复和重塑有一定保护作用,但对心肌梗死后凋亡的作用及具体机制尚不明确.本研究用TRPV1基因敲除(TRPV1-/-)小鼠和野生型(wide type,WT)小鼠建立心肌梗死模型,并外源性给予SP和NK1受体拮抗剂RP67580,用TTC染色法观察梗死的面积,TUNEL法检测心肌细胞凋亡指数,Western印迹方法检测caspase-3、Bcl-2、Bax、p53的蛋白表达.结果发现,心肌梗死24 h后,TRPV1-/-小鼠比WT小鼠梗死面积更大,凋亡指数和caspase-3活性更高,Bcl-2/Bax和p53蛋白表达更低.SP预处理可以明显缩小TRPV1-/-小鼠梗死面积,降低凋亡指数、caspase-3活性和升高Bcl-2/Bax比值,而在WT小鼠中改善不明显.外源性给予RP67580,阻断SP与NK1受体结合后,与相应对照组相比,WT小鼠梗死面积和凋亡指数更大,caspase-3蛋白表达更高,Bcl-2/Bax比值更低;TRPV1-/-小鼠与相应对照组比较,凋亡指数和caspase-3表达升高,Bcl-2/Bax比值降低.研究结果表明,SP可能介导了TRPV1在急性心肌梗死后凋亡中的保护作用.
Transient receptor potential vanilloid 1 (TRPV1) induces angina pectoris and releases substance P (SP) after activation of myocardial ischemia .SP is a member of the tachykinins family, mainly Through the binding and activation of neurokinin 1 (NK1) receptors play a role.TRPV1 and SP in ischemic heart disease on cardiac function recovery and remodeling have a protective effect, but after myocardial infarction apoptosis The role and the specific mechanism is not clear.In this study, TRPV1 knockout (TRPV1 - / -) mice and wild type (WT) mice were established myocardial infarction model and exogenous administration of SP and NK1 receptor antagonist The expression of caspase-3, Bcl-2, Bax and p53 were detected by Western blotting, and the area of infarction was detected by TTC staining and TUNEL method.Results After 24 h of myocardial infarction, TRPV1 - / - mice had larger infarct size, higher apoptotic index and caspase-3 activity, lower expression of Bcl-2 / Bax and p53 protein than those of WT mice.SP preconditioning could significantly reduce infarction in TRPV1 - / - mice Area, decreased apoptotic index, caspase-3 activity and increased Bcl-2 / Bax ratio, while in WT mice After exogenous administration of RP67580, blocking the binding of SP to NK1 receptor, the infarct size and apoptosis index of WT mice were higher and the expression of caspase-3 protein was higher than that of the corresponding control group. The expression of Bcl-2 / Bax ratio was lower in TRPV1 - / - mice than in control group, the apoptotic index and caspase-3 expression were increased and the ratio of Bcl-2 / Bax was decreased in TRPV1 - / - mice.The results showed that SP may mediate the expression of TRPV1 in acute myocardium Protective effect of apoptosis after infarction.