星状神经节阻滞对心力衰竭大鼠心肌细胞凋亡及PI3K/Akt信号通路的影响

Effect of stellate ganglion block on cardiomyocyte apoptosis and expression of PI3K/Akt signaling pathway in cardiac failure rats

目的探讨星状神经节阻滞(SGB)对心力衰竭大鼠心肌细胞凋亡、PI3K/Akt信号通路表达的影响及其相关机制的研究。方法复制心力衰竭雄性大鼠,8周龄,共18只,随机分为SGB组、对照组和假手术组。其中SGB组予以0.1%利多卡因阻滞右侧星状神经节,对照组予以0.9%生理盐水注射至右侧星状神经节部位,假手术组仅切开皮肤至星状神经节暴露而不予阻滞,神经阻滞2周后处死大鼠,取出心脏,酶联免疫吸附试验检测各组心肌组织内肿瘤坏死因子α(TNF-α)和白细胞介素-1β(IL-1β)水平,Western blotting检测各组心肌组织中PI3K、Akt和Caspase-3蛋白的表达,TUNEL检测各组大鼠心肌组织中细胞凋亡情况。结果SGB组TNF-α、IL-1β水平较对照组和假手术组低(P<0.05);SGB组PI3K、Akt蛋白相对表达量较对照组和假手术组高(P<0.05),Caspase-3蛋白相对表达量较对照组和假手术组低(P<0.05);SGB组高倍镜视野下TUNEL染色平均阳性数较对照组和假手术组少(P<0.05)。结论SGB能显著抑制心力衰竭大鼠心肌细胞凋亡,其主要机制在于增强PI3K/Akt信号通路表达,从而保护心脏功能。

Objective To investigate the relationship between apoptosis of myocardial cells in cardiac failure rats and the expressions of PI3K/Akt signaling pathway,and to discuss the relevant mechanism.Methods A total of 18 eight-week-old male cardiac failure rats were randomly divided into stellate ganglion block group,control group and sham operation group,6 rats in each group.Rats in the stellate ganglion block group were given the right stellate ganglion blocking by 0.1%lidocaine intraperitoneal injection,the control group was given the right stellate ganglion blocking by 0.9%normal saline injection and the sham operation group were just only exposed the stellate ganglion without treatment.After 2 weeks of stellate ganglion blocking,all the animals were killed and heart tissue was been retrieved.The level of TNF-αand IL-1βin the myocardial tissue were measured by enzyme-linked immunosorbent assay(ELISA).The critical protein PI3K,Akt and Caspase-3 in apoptotic signaling pathway were analyzed by Western boltting,and cell apoptosis in myocardial tissue were detected by TUNEL staining.Results Compared with the control group and sham operation group,stellate ganglion block can significantly reduce the concentration of TNF-αand IL-1βin the myocardial tissue(P<0.05);compared with the control group and sham operation group,the relative expression levels of PI3K and Akt proteins of myocardial tissue were obviously increased in stellate ganglion block group(P<0.05),and the relative expression levels of Caspase-3 were decreased(P<0.05).Compared with the control group and sham operation group,myocardium cell apoptosis was significantly decreased in the stellate ganglion block group(P<0.05).Conclusions Stellate ganglion block can significantly inhibit the myocardium cell apoptosis in cardiac failure rats.This anti-apoptosis effect is related to the up-regulation of the PI3K/Akt signaling pathway,that help to protect the cardiac function.