瞬时受体电位香草酸亚型1在小鼠心肌梗死后炎症中的保护作用

The protective role of transient receptor potential vanilloid subtype 1 in post-myocardial infarction inflammation process

目的研究瞬时受体电位香草酸亚型1（TRPV1）在心肌梗死（MI）后炎症中的保护作用。方法在TRPV1基因敲除（TRPV1^-/-）小鼠和野生型（WT）小鼠建立MI模型，监测梗死后第3天的梗死面积、炎症细胞渗透、炎症因子和趋化因子的表达水平、心功能和第7天的生存率。结果TRPV1^-/-小鼠MI后7d内的生存率低于野生型小鼠（62．5％比82．1％，P〈0．05）。MI后第3天：TRPV1-/-小鼠的梗死面积（INF）大于野生型小鼠[INF／危险区面积（AAR）：69．5％±3．1％比40．1％±2．6％，P〈0．05]；TRPV1^-/-小鼠的血浆心肌钙蛋白I水平[（0．98±0．16）ng／ml比（0．58±0．15）ng／ml，P〈0．001]、中性粒细胞[（1142±112）／mm^2比（779±50）／mm^2，P〈0．05]和巨噬细胞渗透[（1098±58）／mm^2比（664±49）／mm^2，P〈0．01]均高于野生型小鼠。TRPV1^-/-小鼠的肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1B、IL-6、巨噬细胞趋化蛋白（MCP）-1和巨噬细胞炎症蛋白（MIP）-2表达也明显高于野生型小鼠（均P〈0．05）。此外，与野生型小鼠比较，TRPV1-/-小鼠梗死后收缩末期和舒张末期内径进一步扩大，收缩功能恶化。结论TRPV1基因缺失导致MI后生存率下降，炎症反应增强，心功能恶化，提示TRPV1可能通过抑制炎症和保存心功能而防止梗死扩散和心脏损伤。

Objective To investigate the protective role of transient receptor potential vanilloid subtype 1 （TRPV1） in inflammatory process after myocardial infarction. Methods The survival rate, infarct size, the＇ levels of plasma cardiac troponin Ⅰ, infiltration of inflammatory cells, the levels of cytokines and chemokines, and cardiac function were monitored 3 and 7 days post-myocardial infarction in TRPV1 gene knockout （TRPV1 -/- ） and wild type （WT） mice. Results The survival rate was significantly lower in TRPV1 -/- mice than that in WT mice（62. 5% vs. 82. 1% , P 〈0.05）. The infarct size on day 3 after MI was significantly larger in TRPV1 -/- mice than that in WT mice （ INF/AAR： 69. 5% ± 3.1% vs. 40. 1% ± 2. 6% , P 〈 0. 05 ） . Plasma cardiac troponin I level, number of infiltrated inflammatory cells including neutrophils and macrophages were significant increased in TRPV1 -/- mice compared to WT mice. Expressions of cytokines including TNF-α, IL-1 t5, and IL-6, chemokines including MCP-1 and MIP-2 in the infarct area at 3 and 7 days after MI were significantly higher in TRPV1-/- mice than those in WT mice （all P 〈0. 05 ）. Furthermore, end-systolic and -diastolic diameters were significantly increased and contractile function of the heart significantly reduced in TRPV1 -/- mice compared to WT mice. Conclusion TRPV1 gene deletion results in reduced survival rate, excessive inflammation, deteriorated cardiac function and aggravated left ventricular remodelling after MI, indicating that TRPV1 may prevent infarct expansion and cardiac injury by inhibiting inflammation and reservation cardiac function.