桃仁提取物经NF-κB/COX-2通路对冠心病模型大鼠的保护作用

Protective effect of peach kernel extract on coronary heart disease model rats through nuclear factor-kappaB/cyclooxygenase-2 pathway

目的:基于核因子κB(NF-κB)/环氧合酶2(COX-2)通路,研究桃仁提取物对冠心病(CHD)模型大鼠的保护机制。方法:按照随机数字表法将大鼠分为正常组、模型组、桃仁提取物低、中、高剂量组、阿托伐他汀钙片组,采用高脂饲料饲喂并垂体后叶注射液腹腔注射建立大鼠CHD模型。苏木精-伊红(HE)染色观察心肌组织病理学变化;酶联免疫吸附试验(ELISA)法检测血清中肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、C反应蛋白(CRP)水平;全自动生化分析仪检测血清中总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)水平;实时荧光定量PCR(qRT-PCR)和Western Blot技术检测心肌组织中NF-κB p65、COX-2表达情况。结果:与正常组相比,模型组大鼠心肌组织可见细胞变性、坏死,大量炎性细胞浸润,血清中TNF-α、IL-6、CRP、TC、TG、LDL-C水平、心肌组织中NF-κB p65、COX-2 mRNA及磷酸化NF-κB p65(p-NF-κB p65)、COX-2蛋白水平均显著升高(P<0.05),HDL-C水平显著降低(P<0.05);与模型组相比,桃仁提取物低、中、高剂量组、阿托伐他汀钙片组大鼠心肌组织病理损伤均有不同程度改善,血清中TNF-α、IL-6、CRP、TC、TG、LDL-C水平、心肌组织中NF-κB p65、COX-2 mRNA及p-NF-κB p65、COX-2蛋白水平均显著降低(P<0.05),HDL-C水平显著升高(P<0.05),且呈剂量依赖性。结论:桃仁提取物可能通过阻断NF-κB/COX-2通路进而抑制炎症因子表达,改善血脂水平,减轻心肌损伤,对冠心病大鼠发挥一定保护作用。

Objective:To explore the protective mechanism of peach kernel extract(PKE)on coronary heart disease(CHD)model rats based on nuclear factor kappaB(NF-κB)/cyclooxygenase 2(COX-2)path-way.Methods:According to the random number table,the rats were divided into normal group,mod-el group,PKE low/middle/high dose groups,and atorvastatin calcium group.The CHD model of rat was established by feeding with high-fat diet and intraperitoneal injection of pituitrin.Hematoxylin-eo-sin(HE)staining was used to observe myocardial histopathological changes.The levels of tumor ne-crosis factor-α(TNF-α),interleukin-6(IL-6),C reactive protein(CRP)in serum were detected by en-zyme-linked immunosorbent assay(ELISA).The levels of total cholesterol(TC),triacylglycerol(TG),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)in serum were detected by automatic biochemical analyzer.And the expressions of NF-κB p65 and COX-2 in myocardium were detected by quantitative real-time PCR(qRT-PCR)and Western Blot.Results:Compared with those in normal group,the myocardial tissue in model group showed cell de-generation,necrosis and a large number of inflammatory cells infiltration,the expression levels of TNF-α,IL-6,CRP,TC,TG and LDL-C in serum,NF-κB p65 and COX-2 mRNA,and phosphor-ylated NF-κB p65(p-NF-κB p65)and COX-2 proteins in myocardium were significantly increased(all P<0.05),LDL-C level was significantly decreased(P<0.05);Compared those in model group,the pathological changes of myocardial tissue in low,middle,and high dose of PKE groups and atorvas-tatin calcium group were improved in varying degrees,the expression levels of TNF-α,IL-6,CRP,TC,TG,and LDL-C in serum,NF-κB p65,COX-2 mRNA,p-NF-κB p65,and COX-2 protein in myocardium were significantly decreased(P<0.05),LDL-C level was significantly increased(P<0.05),and the changes were dose-dependent.Conclusion:Peach kernel extract may inhibit the ex-pression of inflammatory factors,improve blood lipid levels,and reduce myocardial damage by block-ing the NF-κB/COX-2 pathway,and have a certain protective effect on CHD rats.