神经调节蛋白-1对心肌梗死大鼠心脏交感神经重构的保护效应研究

Effect of neuregulin-1 on cardiac sympathetic neural remodeling in rats with myocardial infarction

目的观察神经调节蛋白-1(NRG-1)对心肌梗死大鼠心脏交感神经重构的影响。方法 2014年9—12月在武汉大学心血管病研究所完成实验。将18只SD大鼠按随机数字表法分为假手术组(n=6)、心肌梗死组(n=6)、NRG-1干预组(n=6);以冠状动脉前降支结扎方法建立心肌梗死模型,NRG-1干预组于心肌梗死模型建立后每天经鼠尾静脉给予NRG-1(0.01μg/g)干预,连续7 d;心肌梗死组则给予生理盐水干预,假手术组仅开胸切开心包膜不结扎冠状动脉。所有大鼠均于术后7 d利用Real-time PCR技术和Western-blot技术检测梗死周边区心肌组织交感神经重构标志物——酪氨酸羟化酶(TH)和生长相关蛋白43(GAP43)的mRNA和蛋白水平。结果心肌梗死组梗死周边区心肌组织TH、GAP43的mRNA水平较假手术组明显升高(P<0.05),而NRG-1干预组梗死周边区心肌组织TH、GAP43的mRNA水平均明显低于心肌梗死组(P<0.05)。与TH、GAP43的mRNA水平变化一致,心肌梗死组TH、GAP43的蛋白表达量明显增高,而NRG-1的干预明显降低了TH、GAP43的蛋白表达(P<0.05)。结论NRG-1可降低大鼠心肌梗死后交感神经重构,有利于稳定心电活动,改善心功能,是其发挥心肌保护效应的机制之一。

Objective To investigate the effect of neuregulin 1 （NRG-1） on cardiac sympathetic neural remodeling in rats with myocardial infarction （MI）.Methods The experiment was carried out in the Institute of cardiovascular disease, Wuhan University from September 2014 to December 2014.SD rats were randomly divided into sham operation group （SO group,n=6）, myocardial infarction group （MI group,n=6） and NRG-1 group （n=6）.Rats in MI and NRG-1 group underwent coronary artery ligation.NRG-1 （0.01 μg/g） was injected through the tail vein for seven days after MI operation in NRG-1 group.The same volume of saline was given to the rats in MI group.Rats in the SO group underwent thoracotomy and pericardiotomy but without ligation.Seven days after the operation, the Real Time PCR and Western blot technology were used to detect the mRNA and protein amount of TH （tyrosine hydroxylase, TH） and GAP43 （growth associated protein 43, GAP43） in the myocardial tissues from the infarct border zone.Results Compared with the SO group, the level of TH and GAP43 mRNA in the infarct border zone in the MI group increased significantly, （1.56±0.07 vs.0.76±0.27,P=0.001;1.32±0.09 vs 0.98±0.13,P=0.004）, the administration of NRG-1 for 7 days decreased the mRNA level of TH （0.71±0.10） and GAP43 （0.96±0.06） in the infarct border zone of the NRG 1 group, which were significant lower than those of the MI group （P=0.001,P=0.018）.The changes of the protein expression of TH and GAP43 were consistent with the changes of mRNA level in the three groups as the increased protein expression of TH and GAP43 in the MI group and the decreased expression in the NRG 1 group.Conclusion NRG-1 showed elimination effects in sympathetic neural remodeling after myocardial infarction, which is beneficial to improve cardiac electrical stability and contractile function.