摘要
目的 探讨毛蕊花糖苷(verbascoside,Verb)对冠心病(CHD)大鼠炎症及脂代谢的影响.方法 将SD大鼠随机分为对照组、模型组、毛蕊花糖苷低、中、高剂量组,每组12只.对照组大鼠正常饲料喂养,其他组大鼠高脂饮食联合腹腔注射垂体后叶素诱导冠心病模型.建模后,对照组和模型组大鼠均每天灌胃2 mL生理盐水,低、中、高剂量组大鼠分别每日灌胃2 mL剂量为20,40,80 mg/kg的毛蕊花糖苷,共灌胃4周.末次给药后24 h,分别检测各组大鼠的心功能指标[射血分数(EF)和短轴缩短率(FS)]、血清心肌损伤标志物[肌酸激酶同工酶MB(CK-MB)和乳酸脱氢酶(LDH)]、血清脂代谢指标[总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)和游离脂肪酸(FFA)]和血清炎症指标[肿瘤坏死因子-α(TNF-α)、细胞间黏附分子-1(ICAM-1)和单核细胞趋化因子-1(MCP-1)].通过苏木素伊红(HE)染色观察心肌形态.通过qRT-PCR检测心肌组织中AMP激活的蛋白激酶α(AMPKα)、过氧化物酶体增殖物激活受体α和γ(PPAR-α和PPAR-γ)和PPAR-y激活分子1α(PGC-1α)的mRNA水平.通过Western blot检测心肌组织中核因子-κB(NF-κB)p65和AMPKα的磷酸化水平.结果 与对照组比较,模型组大鼠的EF和FS降低(P＜0.05),血清中CK-MB、LDH、TC、TG、LDL-C、FFA、TNF-α、ICAM-1 和 MCP-1 水平升高(P＜0.05),血清 HDL-C 水平降低(P＜0.05),心肌组织中 NF-κB p65 的磷酸化水平升高(P＜0.05),心肌组织中AMPKα、PPAR-α、PPAR-γ和PGC-1α mRNA水平和AMPKα的磷酸化水平降低(P＜0.05).与模型组比较,低、中和高剂量组大鼠的EF和FS升高(P＜0.05),血清中CK-MB、LDH、TC、TG、LDL-C、FFA、TNF-α、ICAM-1和MCP-1水平降低(P＜0.05),血清HDL-C水平升高(P＜0.05),心肌组织中NF-κB p65的磷酸化水平降低(P＜0.05),心肌组织中AMPKα、PPAR-α、PPAR-γ和PGC-1α mRNA水平和AMPKα的磷酸化水平升高(P＜0.05).与低剂量组比较,中和高剂量组大鼠的 EF 和 FS 升高(P＜0.05),血清中 CK-MB、LDH、TC、TG、LDL-C、FFA、TNF-α、ICAM-1 和 MCP-1 水平降低(P＜0.05),血清HDL-C水平升高(P＜0.05),心肌组织中NF-κB p65的磷酸化水平降低(P＜0.05),心肌组织中AMPKα、PPAR-α、PPAR-γ和PGC-1α mRNA水平和AMPKα的磷酸化水平升高(P＜0.05).结论 毛蕊花糖苷有效改善了冠心病大鼠的心功能,减轻了心肌损伤,其机制可能与抑制NF-κB介导的炎症反应和激活AMPK介导的脂代谢基因转录和表达有关.
Abstract
Objective To investigate the effects of verbascoside(Verb)on inflammation and lipid metabolism in rats with coronary heart disease(CHD).Methods SD rats were randomized into control group,model group,low,medium and high dose verbascoside groups,with 12 rats in each group.Rats in control group were fed with normal diet,and the coronary heart disease model rats were induced by high fat diet combined with intraperitoneal injection of pituitrin.After modeling,rats in control group and model group were intragastrically infused with 2 mL saline,while rats in low,medium and high dose verbascoside groups were intragastrically infused with 2 mL of 20,40 and 80 mg/kg verbascoside.All rats were given intragastric administration for 4 weeks.The indexes of cardiac function[ejection fraction(EF)and fraction shortening(FS)],serum markers of myocardial injury[creatine kinase isoenzyme MB(CK-MB)and lactate dehydrogenase(LDH)],serum lipid metabolism indexes[total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C)and free fatty acid(FFA)]and serum inflammatory markers[tumor necrosis factor-α(TNF-α),intercellular adhesion molecule-1(ICAM-1)and monocyte chemoattractant protein-1(MCP-1)]were detected in each group 24 h after the last administration.Myocardial morphology was observed by hematoxylin eosin(HE)staining.The mRNA levels of AMP-activated protein kinase α(AMPKα),peroxisome proliferator-activated receptors-α(PPAR-α),PPAR-γand PPAR-y-activated molecule 1α(PGC-1α)in myocardial tissues were measured by qRT-PCR.The phosphorylation levels of nuclear factor-κB(NF-κB)p65 and AMPKα in myocardial tissue were detected by Western blot.Results Compared with control group,EF and FS were decreased in model group(P＜0.05),serum levels of CK-MB,LDH,TC,TG,LDL-C,FFA,TNF-α,ICAM-1 and MCP-1 were increased(P＜0.05),serum HDL-C level was decreased(P＜0.05),NF-κB p65 phosphorylation level was increased in myocardial tissue(P＜0.05),and AMPKα,PPAR-α,PPAR-γ,PGC-1α mRNA levels and AMPKα phosphorylation level were decreased in myocardial tissue(P＜0.05).Compared with model group,EF and FS in low,medium and high dose verbascoside groups were increased(P＜0.05),serum levels of CK-MB,LDH,TC,TG,LDL-C,FFA,TNF-α,ICAM-1 and MCP-1 were decreased(P＜0.05),serum HDL-C level was increased(P＜0.05),NF-κB p65 phosphorylation level was decreased in myocardial tissue(P＜0.05),and AMPKα,PPAR-α,PPAR-γ,PGC-1α mRNA levels and AMPKα phosphorylation level were increased in myocardial tissue(P＜0.05).Compared with low dose verbascoside group,EF and FS were increased in medium and high dose verbascoside groups(P＜0.05),serum levels of CK-MB,LDH,TC,TG,LDL-C,FFA,TNF-α,ICAM-1 and MCP-1 were decreased(P＜0.05),serum HDL-C level was increased(P＜0.05),NF-κB p65 phosphorylation level was decreased in myocardial tissue(P＜0.05),and AMPKα,PPAR-α,PPAR-γ,PGC-1α mRNA levels and AMPKα phosphorylation level were increased in myocardial tissue(P＜0.05).Conclusion Verbascoside can effectively improve the cardiac function and reduce the myocardial injury in rats with coronary heart disease,which may be related to the inhibition of NF-κB-mediated inflammation and the activation of AMPK-mediated lipid metabolism gene transcription and expression.
维普
万方数据