机构地区:[1]天津中医药大学研究生院,300193 [2]天津市中医药研究院附属医院糖尿病科,300120
出 处:《国际内分泌代谢杂志》2018年第1期10-14,F0003,共6页International Journal of Endocrinology and Metabolism
摘 要:目的 研究自拟脉痹方对糖尿病大鼠后肢动脉血凝素样氧化低密度脂蛋白受体(LOX)-1表达的影响及机制.方法 60只Sprauge-Dawley大鼠按照随机数字表法随机取10只作为正常对照组,50只予高糖、高脂饮食联合尾静脉注射链脲佐菌素(25 mg/kg)建立糖尿病模型,成模后按照随机数字表法分为非药物干预组、西洛他唑干预组(10 mg· kg-1 ·d-1)、低剂量脉痹方干预组(12g·kg-1·d-1)、中剂量脉痹方干预组(24g· kg-1 ·d-1)、高剂量脉痹方干预组(48g· kg-1·d-1),每组10只.灌胃4周后,测定大鼠的体重、血糖、肝功能、肾功能、总胆固醇、甘油三酯、高密度脂蛋白-胆固醇、低密度脂蛋白-胆固醇(LDL-C);HE染色观察后肢动脉内膜组织的形态;Western印迹法检测后肢动脉LOX-1、核因子-KB p65、血管细胞黏附分子-1(VCAM-1)蛋白的表达.结果 造模后糖尿病大鼠较非糖尿病大鼠体重下降明显,血糖升高(F =4.63、120.27,P均<0.05),药物干预4周后各组肝、肾功能无差异(P均>0.05).与非药物干预组相比,中、高剂量脉痹方干预组血清总胆固醇、LDL-C明显下降,正常对照组、西洛他唑干预组及低、中、高剂量脉痹方干预组血清甘油三酯较非药物干预组明显下降(F=4.10、4.97、17.23,P均<0.01).HE染色可见非药物干预组后肢动脉中膜细胞黏液变性,经药物干预后,各组均有不同程度的改善,其中中剂量脉痹方干预组和高剂量脉痹方干预组改善较明显.低、中、高剂量脉痹方干预组及西洛他唑干预组后肢动脉LOX-1、VCAM-1蛋白表达均较非药物干预组下降(F=13.25、43.01,P均<0.01),西洛他唑干预组、高剂量脉痹方干预组核因子-KB p65较非药物干预组下降明显(F=13.83,P<0.01).结论 自拟脉痹方可下调糖尿病大鼠后肢动脉LOX-1的表达,并通过降低核因子-KB p65抑制VCAM-1的表达.Objective To investigate the effect and related mechanism of Zinimaibi Decoction on the expression of lectin-like oxidized low-density lipoprotein receptor (LOX)-1 in the hindlimb arteries of diabetic rats.Methods A total of sixty Sprauge-Dawley rats were included in this study.Ten rats were randomly selected as normal control group according to random number table method,whereas all the other rats were fed with high-glucose and high-fat diet combined with the injection of streptozotocin (25 mg/kg) from tail vein to induce diabetes.After successful modeling,all diabetic rats were randomly divided into non-drug intervention group,cilostazol group(10 mg · kg-1 · d-1),low dose of Maibi Decoction group (12 g · kg-1 · d-1),medium dose of Maibi Decoction group(24 g · kg-1 · d-1) and high dose of Maibi Decoction group(48 g · kg-1 · d 1)according to random number table method,with 10 rats in each group.After 4 weeks of intervention,body weight,blood glucose,liver function,renal function and total cholesterol (CHO),triglyceride (TG),high density lipoprotein-cholesterol (HDL-C) and low density lipoprotein-cholesterol(LDL-C) were examined.HE staining was used to observe the morphilogical changes of hindlimb artery intima.Western blotting was used to analyze the expression of LOX-1,nuclear factor-κB(NF-κB) p65 and vascular cell adhesion molecule (VCAM)-1 of hindlimb.Results The weight of diabetic rats were decreased and blood glucose were increased significantly compared with non-diabetic rats after modeling (F =4.63,120.27,all P < 0.05).No significant difference was found in liver and renal function among groups 4 weeks after drug intervention (all P > 0.05).The serum CHO and LDL-C level in the medium and high dose of Maibi Decoction group were downregulated compared with non-drug intervention group,the serum TG level in normal control group,cilostazol group,and all Maibi Decoction groups were decreased significantly compared with non-drug intervention gr
关 键 词:自拟脉痹方 糖尿病性下肢动脉粥样硬化 血凝素样氧化低密度脂蛋白受体-1 核因子-κB p65 血管细胞黏附分子-1
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