摘要
目的:探讨线粒体三磷酸腺苷(ATP)敏感性钾离子通道(mito-KATP)开放剂二氮嗪对冠心病大鼠心肌细胞凋亡及炎症反应的影响及作用机制.方法:SD大鼠构建冠心病模型后分为模型组、二氮嗪低剂量组、二氮嗪中剂量组、二氮嗪高剂量组,正常大鼠作为空白对照组,二氮嗪低剂量组、中剂量组、高剂量组大鼠分别灌胃给予二氮嗪3、5、7 mg/kg,治疗14 d后检测大鼠血清肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β、IL-6、三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、3-羟基-3-甲基戊二酸单酰辅酶A还原酶(HMGR)水平.苏木精-伊红(HE)染色观察大鼠心肌组织损伤.蛋白免疫印迹法(Western Blot)检测心肌组织 Bax、Cleaved Caspase-3、Bcl-2、甘油醛-3-磷酸脱氢酶(GAPDH)、核因子-κB(NF-κB)、磷酸化 NF-κB(p-NF-κB)、过氧化物酶体增殖物激活受体γ(PPAR γ)相对表达水平.结果:与模型组比较,二氮嗪低剂量组、中剂量组、高剂量组大鼠血清IL-1β、IL-6、TG、TC、LDL-C、HDL-C、HMGR水平明显降低,心肌细胞损伤明显减少,并且凋亡相关蛋白Bax和Cleaved Caspase-3表达下调,Bcl-2表达明显上调,p-NF-κB表达明显降低,PPARγ表达明显上调,差异均有统计学意义(P＜0.05).结论:二氮嗪可明显缓解冠心病大鼠心肌损伤,其机制可能与调控PPARγ和NF-κB信号通路有关.
Abstract
Objective:To investigate the effect of diazoxide on cardiomyocyte apoptosis and inflammatory response in rats with coronary heart disease(CHD).Methods:SD rats were divided into model group,diazoxide low-dose group,diazoxide medium-dose group,and diazoxide high-dose group.Normal rats served as the blank control group,and the rats in diazoxide low-dose group,medium-dose group,high-dose group were administered 3,5,and 7 mg/kg of diazoxide by gavage respectively.After 14 days of treatment,serum levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,IL-6,triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),and 3-hydroxy-3-methylglutaryl-coenzyme A reductase(HMGR)were measured.Hematoxylin-eosin(HE)staining was used to observe myocardial tissue injury.Western Blot was used to detect Bax,Cleaved Caspase-3,Bcl-2,glyceraldehyde-3-phosphate dehydrogenase(GAPDH),nuclear factor-κB(NF-κB),phosphorylated NF-κB(p-NF-κB),peroxisome proliferator-activated receptor y(PPARy).Results:Compared with the model group,the serum levels of IL-1β,IL-6,TG,TC,LDL-C,HDL-C,and HMGR were significantly lower in the diazoxide low-dose group,middle dose group,and high-dose group.Additionally,myocardial cell damage was significantly reduced and the expression of apoptosis-related proteins Bax and Cleaved Caspase-3 was down-regulated.The expression of Bcl-2 was significantly up-regulated while the expression of p-NF-κB was significantly decreased.Furthermore,the expression of PPARγ was significantly up-regulated(P＜0.05).Conclusion:Diazoxide can significantly alleviate myocardial injury in CHD rats,and its mechanism may relate the regulation of PPAR γ and NF-κB signal pathway.
维普
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