中文摘要：

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，NKI）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（widetype，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24h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、easpase-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．

英文摘要：

Myocardial ischemia causes the release of protons and bradykinin, which activated transient receptor potential vanilloid 1 （TRPV1） channel expressed in cardiac sensory nerve terminals, to cause angina. Our previous study showed that ischemia induced TRPV1 activation and consequent sensory neurotransmitter substance P （SP） release played a protective role in heart function. However, whether SP mediate TRPV1 protective role in apoptosis is unclear. In this study, myocardial infarction （MI） models were established in wild type （WT） and TRPVI-null mutant （TRPV1 -/- ） mice. SP and RP67580 （a NK1 receptor antagonist） were pretreated before MI. The infarct size was detected by TTC stain; the apoptosis index was determined by TUNEL; the expression of caspase-3, Bcl-2, Bax and p53 were detected by Western blot 24 hours post myocardial infarction. Compared with sham group, infarct size, apoptosis index, caspase-3 activity were increased post MI in both TRPV1 -/- and WT mice. The expression levels of p53 and Bcl-2/Bax were decreased in both strains after MI. TRPV1-/- mice presented a greater infarct size, apoptosis index, elevated activity of caspase-3, and lower expression of p53 and Bcl-2/Bax, compared with WT mice. Pretreatment with substance P, the Bcl-2/Bax and activity of caspase-3 were increased in both strains, more significant changes were showed in TRPV1-/- mice. However, the administration of SP significant decreased the infarct size and apoptosis index in TRPV1 -/- mice but not in WT mice. Blockade of the NK1 receptor with RP67580 reduced the infarct size, apoptosis index, Bcl-2/Bax and increased activity of caspase-3 in both strains, compared with corresponding control group. These data show that SP may mediate the protective role of TRPV1 in apoptosis post acute myocardial infarction.