芝麻素影响冠心病大鼠心肌细胞凋亡的机制

Mechanism of sesamin on myocardial apoptosis in rats with coronary heart disease

目的探讨芝麻素对冠心病(coronary heart disease,CHD)大鼠心肌细胞凋亡的影响及可能作用机制。方法取64只大鼠给予高脂饲料饲养,建立CHD模型,随机分为模型组,芝麻素低剂量、中剂量和高剂量组,每组16只,剩余16只未建模大鼠为对照组。按照每日2 mL,芝麻素低剂量、中剂量和高剂量组分别灌胃40、80、160 mg·kg^(-1)芝麻素,对照组和模型组灌胃羧甲基纤维素钠溶液;连续28 d。比较各组大鼠脂代谢、血管内皮功能、心肌组织形态学和心肌细胞凋亡率及心肌组织中白细胞介素-6(interleukin-6,IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、一氧化氮(nitric oxide,NO)、磷脂酰肌醇3-激酶(phosphoinostitide-3 kinase,PI3K)、磷酸化丝氨酸/苏氨酸激酶(phospho-serine/threonine kinase,p-Akt)、磷酸化一氧化氮合酶(phospho-endothelial nitric oxide syhthase,p-eNOS)、半胱氨酸天冬氨酸蛋白酶12(cysteinyl aspartate specific proteinase-12,Caspase-12)、细胞间黏附分子-1(intercellular adhesion molecule-1,ICAM-1)蛋白水平的差异。结果与模型组比较,芝麻素各剂量组三酰甘油(triglyceride,TG)、胆固醇(cholesterin,TC)、乙酰胆碱(acetylcholine,ACH)处理血管最大舒张程度、IL-6、TNF-α、细胞凋亡率以及Caspase-12、ICAM-1蛋白水平呈剂量依赖性降低(P<0.05);高密度脂蛋白胆固醇(high-density lipoprotein choleste-rol,HDL-C)、NO、PI3K、p-Akt和p-eNOS蛋白水平较模型组升高,也呈现剂量依赖性(P<0.05)。结论芝麻素可有效改善CHD大鼠脂代谢和血管内皮功能,抑制心肌细胞凋亡,降低心肌组织Caspase-12、ICAM-1蛋白表达水平,这可能与激活PI3K-Akt-eNOS信号通路有关。

Objective To explore the effect of sesamin on myocardial apoptosis in rats with coronary heart disease(CHD)and its possible mechanism.Methods 64 rats were fed with high-fat diet to establish CHD models,randomly divided into model group,sesamin low,medium and high dose groups,with 16 rats in each group the remaining 16 unmodeled rats served as control group.According to 2 mL a day,the low,medium and high dose groups of sesamin were gavaged with 40,80 and 160 mg·kg^(-1) sesamin respectively,while the control group and the model group were gavaged with sodium carboxymethyl cellulose solution for 28 days.The rat lipid metabolism,vascular endothelial function,myocardial tissue morphology,cardiomyocyte apoptosis and interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),nitric oxide(NO)levels,phosphoinositide 3-kinase(PI3K),phospho-serine/threonine kinase(p-Akt),phospho-endothelial nitric oxide synthase(p-eNOS),cysteinyl aspartate specific proteinase-12(Caspase-12),intercellular adhesion molecule-1(ICAM-1)protein expression were compared.Results Compared with the model group,the triglyceride(TG),cholesterin(TC),the degree of maximum relaxation of acetylcholine(ACH)treated vessels,IL-6,TNF-α,apoptosis rate and the levels of Caspase-12,ICAM-1 protein were decreased(P<0.05),the high-density lipoprotein cholesterol(HDL-C),NO levels and PI3K,p-Akt,p-eNOS protein levels were increased(P<0.05).The TC,TG,the degree of vascular relaxation of ACH treated vessels,apoptosis rate,IL-6,TNF-αand Caspase-12,ICAM-1 protein levels were reduced,while the HDL-C,NO levels as well as PI3K,p-Akt,p-eNOS protein levels were increased in a dose-dependent manner(P<0.05).Conclusion Sesamin can effectively improve lipid metabolism and vascular endothelial function in CHD rats,inhibit myocardial cell apoptosis,and reduce the expression of Caspase-12 and ICAM-1 proteins in myocardial tissue,which may be related to the activation of PI3K-Akt-eNOS signaling pathway.