尼可地尔预处理对冠状动脉微栓塞PDCD4/NF-κB/TNF-α通路的影响及意义

Effects of pretreatment with nicorandil on PDCD4/NF-κB/TNF-α pathway in coronary microembolization

目的探讨尼可地尔预处理对小猪冠状动脉微栓塞（coronary microembolization，CME）后心肌的保护作用，以及对程序性细胞死亡因子4（programmed cell death 4，PDCD4）／核因子．KB（nuclear facotr-kapa B，NF-κB）／肿瘤坏死因子α（tumor necrosis factor α，TNF-α）信号通路的影响。方法15头巴马小猪随机（随机数字法）分为假手术组（Sham组）、微栓塞组（CME组）、CME＋尼可地尔组，每组5只。经微导管左前降支注入微栓塞球构建CME模型组，注射等量生理盐水构建Sham组。尼可地尔组于CME前30min通过耳缘静脉注射尼可地尔（150μg／kgo心脏超声用于检测心功能指标；荧光定量PCR检测心肌组织PDCD4与TNF-αmRNA表达；Western blot检测心肌组织PDCD4和TNF-α蛋白表达；凝胶电泳迁移率转变分析（EMSA）用于评价NF—κB活性。结果（1）心脏超声结果显示，与Sham组比较，CME组心功能明显下降，血清cTnI水平明显较高，而CME＋尼可地尔组心功能差异无统计学意义，但血清cTnI水平明显升高（P〈0．05）；与CME组比较，CME＋尼可地尔可减少CME引起的心功能损伤，降低血清cTnI水平（P〈0．05）。（2）与Sham组比较，CME组和CME＋尼可地尔组PDCD4、NF—κB与TNF-α的表达量均显著增加（均P〈0．05）；与CME组比较，CME＋尼可地尔组PDCD4、NF-κB与TNF-α的表达量均显著降低（均P〈0．05）。结论尼可地尔预处理可以有效改善CME所致的心肌损伤，该效应可能是通过阻断心肌细胞PDCD4／NF-κB／TNF-α信号通路实现。

Objective To investigate myocardium after coronary microembolization the role of nicorandil pretreatment on protecting （CME） and on the PDCD4/NF-κB/TNF-α signaling pathway in miniature pigs. Methods Fifteen Bama miniature pigs were randomly（random number） divided into the sham operation group （sham group）, microembolization group （CME group） and CME plus nicorandil group, with 5 pigs in each group. polyethylene microspheres via microcatheter into the left group were injected with the same amount of saline. Pigs The CME model was constructed by injecting anterior descending artery, and pigs in the sham in the CME plus nicorandil group were injected intravenously with nicorandil （150 μg/kg） via ear vein 30 min before CME. Cardiac function indexes were measured using cardiac ultrasonography. The expression of PDCD4 and TNF-α mRNA in myocardium were detected by fluorescence quantitative PCR, and the protein expression of PDCD4 and TNF-α in rnyocardium were detected by Western blotting. NF-κB activation was evaluated by electrophoretic mobility shift assay. Results （1） Cardiac function was significantly lower and the level of serum cTnI was significantly higher in the CME group compared with the sham group. CME reduced myocardial systolic dysfunction and left ventricular dilatation. The CME plus nicorandil group showed improved CME-induced cardiac function and reduced serum cTnI level when compared with the CME Group （P 〈 0.05）. （2） Compared with the CME group, the CME plus nicorandil group showed lower PDCD4 and TNF-α expression and NF-κB activity as well as improved cardiac function （P 〈 0.05）. Conclusions The pretreatment of nicorandil effectively reduced the myocardial damage caused by CME, mainly through inhibiting the PDCD4/NF-κB/TNF-α pathway in cardiomyocytes.