丹参多酚酸盐保护体外循环后心脏功能的研究

目的探讨细胞自噬参与体外循环术(cardiopulmonary bypass,CPB)后心脏功能减退的主要分子机制及丹参多酚酸盐治疗对CPB后心脏功能的改善。方法健康雄性中华小型猪15只,随机分为CPB组6只、治疗组6只和对照组3只。监测各组小型猪心功能、血流动力学及炎性因子的变化,以及免疫组织化学测定的凋亡指数和心肌、肾小球超微结构的改变。应用Western blot法定量分析各组细胞自噬通路相关信号的改变。结果与对照组比较,CPB组CPB后2h白细胞介素(IL)1β、TNF-α、IL-10水平明显升高,伴随有心脏功能的减退。与CPB组比较,治疗组CPB后2hIL-1β、IL-2、TNF-α水平明显下降,心脏功能明显好转,差异有统计学意义(P<0.05)。CPB后2h,CPB组哺乳动物雷帕霉素靶蛋白(mTOR)信号通路活性增强,但LC3-Ⅱ/LC3-Ⅰ比值仍较对照组明显增高,而治疗组mTOR信号通路活性较CPB组进一步增强,伴LC3-Ⅱ/LC3-Ⅰ比值较CPB组明显下降。结论丹参多酚酸盐能保护CPB后心脏功能,这与其参与AMP蛋白激酶和mTOR信号通路调控抑制CPB后心肌细胞自噬活性有关,也与其抗炎症和氧化应激相关。

Salvionate protects cardiac function after cariopulmonary bypass

Objective To study the major molecular mechanism of myocytes autophagy underlying cardiac hypofunction and the effect of salvionate on cardiac function after cardiopulmonary bypass(CPB).Methods Fifteen healthy male Chinese pigs were randomly divided into CPB group(n=6),salvionate treatment group(n=6) and control group(n=3).Their cardiac function,hemodynamic parameters and inflammatory factors were measured,and apoptosis index and ultrastructure of myocardium and glomeruli were assayed by immunohistochemistry.Myocytes autophagy pathway-related signals were detected by Western blot.Results The serum IL-1β,TNF-α and IL-10 levels were significantly higher whereas the cardiac function level was lower in CPB group than in control group 2 h after CPB.The serum IL-1β,IL-2,and TNF-α levels were significantly lower in salvionate treatment group than in CPB group 2 h after CPB.The activity of mTOR signal pathway and the LC3-Ⅱ/LC3-Ⅰ ratio were significantly higher in CPB group than in control group whereas the activity of mTOR signal pathway was significantly higher while the LC3-Ⅱ/LC3-Ⅰ ratio was significantly lower in salvionate treatment group than in CPB group 2 h after CPB.Conclusion Salvionate can protect cardiac function after CPB,which is related with its involvement in inhibiting AMP kinase activity and autophagy of myocytes through the mTOR signal pathway,as well as its anti-inflammation and anti-oxidation stress effects.