丹蛭降糖胶囊对糖尿病大鼠心肌组织TLR4、TNF-α、IL-8表达和心脏病理影响

Impacts of Dan Zhi Jiang Tang Capsule on Myocardial TLR4,TNF-α and IL-8 and the Cardiopathologic Changes in Diabetic Rats

目的:本文主要探讨丹蛭降糖胶囊(Dan Zhi Jiang Tang Capsule,DJC)对糖尿病大鼠心肌组织Toll样受体4(Toll-Like Receptor 4,TLR4)、肿瘤坏死因子α(Tumor Necrosis Factorα,TNFα)、白介素-8(Interleukin-8,IL-8)的干预及对心脏病理的影响。方法:取50只雄性大鼠,除正常组8只外,其余组给予高脂饲料喂养4周,按35 mg·kg-1给大鼠腹腔注射链脲佐菌素(Streptozotocin,STZ)1次,建立糖尿病大鼠模型。造模成功后将大鼠随机分为模型组、DJC高剂量组、DJC低剂量组、吡格列酮组。DIC高、低剂量组每日分别给予1.08、0.54 g·kg-1灌胃,吡咯列酮组予10 mg·kg-1灌胃,模型组、正常组予以等量生理盐水灌胃,连续8周,并继续喂高脂饲料;测定血糖、Hb A1c、血脂;观察心肌组织TLR4、TNF-α、IL-8蛋白表达。结果:与正常组相比,模型组大鼠心肌组织TLR4、TNFα、IL-8表达增加(P<0.01);与模型组相比,DJC高、低剂量组大鼠心肌组织TLR4、TNFα、IL-8表达减少(P<0.05或P<0.01)。病理染色发现模型组大鼠心肌组织严重受损,DJC高剂量组大鼠心肌组织损伤程度明显减轻,且优于低剂量组和吡格列酮组。与正常组相比,模型组大鼠血糖、Hb A1c、TG、TC、LDL-C水平明显升高(P<0.05或P<0.01),与模型组相比,DJC高、低剂量组大鼠血糖、Hb A1c、TG、TC、LDL-C水平明显下降(P<0.05或P<0.01)。结论:丹蛭降糖胶囊能够明显下调TLR4、TNF-α、IL-8高表达水平,减轻糖尿病大鼠心肌病变程度;具有良好的降糖调脂作用。

This study chiefly aimed at investigating the effects of Dan Zhi Jiang Tang Capsule（DJC） on myocardial Toll-like receptor 4（TLR4）, tumor necrosis factor α（TNFα） and interleukin-8（IL-8） and the cardiopathologic changes indiabetic rats. Fifty male rats, excluding 8 rats in the control group, had been administered with high fat forage for 4weeks, which established the diabetic rat model combined with the intraperitoneal injection of streptozotocin（STZ） at35 mg·kg-1. The established model rats were randomly divided into the model group, the DJC high-dose group, the DJClow-dose group and the pioglitazone group. The rats in the model group and the control group were intragastricallyadministered with DJC at 1.08 and 0.54 g·kg-1each day, while those of the pioglitazone group were treated withpioglitazone at 10 mg·kg-1each day, and those of the model group and control group with saline of the same volume. Theadministrations lasted 8 weeks with the continues high-fat diet. The levels of TLR4, TNFα and IL-8 protein inmyocardium of the rats were determined, and so were the blood glucose, HbA1cand blood lipids. Compared with thecontrol group, the expressions of myocardial TLR4, TNFα and IL-8 in the model group were significantly increased（P〈0.01）. The expressions of TLR4, TNFα and IL-8 in the DJC high-dose and low-dose groups were significantly decreased（P〈0.05 or P〈0.01）. The cardiopathological report showed severe myocardial lesion in the model group. However,myocardial lesion in the DJC high-dose group was significantly mitigated, which presented better therapeutic effects thanthe DJC low-dose group and the pioglitazone group. The levels of blood glucose, HbA1c, TG, TC, LDL-C in the modelgroup were significantly higher than those in the control group（P〈0.05 or P〈0.01）. The levels of blood glucose, HbA1c,TG, TC and LDL-C were significantly decreased in the DJC high-dose and low-dose groups in comparison with themodel group（P〈 0.05 or P〈 0.01）. In conclusion, DJC down-regulated the expressions of TLR4, TNFα and IL-8 andimproved the degree of myocardial lesion in the diabetic rats, showing favorable hypoglycemic and lipid-lowering effects.