替米沙坦对糖尿病大鼠主动脉组织血凝素样氧化型低密度脂蛋白受体1表达的影响
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The Effects of Telmisartan on Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Expression on Aortas in Streptozotocin-Induced Diabetic Rats
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    目的观察糖尿病大鼠主动脉组织中血凝素样氧化型低密度脂蛋白受体1(lectin-like oxidized low-den-sity lipoprotein receptor-1,LOX-1)的表达以及替米沙坦的干预作用,从而探讨糖尿病动脉粥样硬化的发病机制。方法雄性6周龄SD大鼠32只,分为对照组(n=8)及实验组(n=24),实验组予高脂高糖饲料喂养4周后应用链脲佐菌素45 mg/kg腹腔注射一次建立糖尿病模型。造模成功的大鼠再分为糖尿病组(n=9)和替米沙坦组(n=11),对照组和糖尿病组给予蒸馏水灌胃,替米沙坦组予替米沙坦20 mg/kg灌胃,药物干预共8周。全自动生化分析仪检测血脂水平,应用HE染色观察主动脉弓病理组织学变化,应用Real-time PCR和Western blot杂交技术观察大鼠主动脉组织中LOX-1 mRNA及蛋白表达水平的变化及替米沙坦对LOX-1表达的影响。结果三组大鼠间总胆固醇(P=0.13)、甘油三酯(P=0.35)差异无统计学意义。糖尿病组高密度脂蛋白较对照组(0.99±0.12 mmol/L比1.37±0.23 mmol/L)显著降低(P=0.001),且低密度脂蛋白(0.48±0.08 mmol/L比0.34±0.03 mmol/L)有明显升高(P=0.001)。大鼠主动脉病理组织学提示对照组内膜层薄,内皮细胞排列整齐,内膜光滑;糖尿病组可见局部内皮细胞脱落,内膜不光滑,局部内膜增厚;替米沙坦组无明显改善;三组均未见明显动脉粥样斑块形成。与对照组相比,糖尿病组LOX-1 mRNA(0.316±0.055比0.154±0.029)和蛋白(1.271±0.238比0.739±0.113)的相对表达量增高(P=0.000),替米沙坦干预后,LOX-1 mRNA(0.192±0.030比0.316±0.055)和蛋白(0.691±0.198比1.271±0.238)的相对表达量较糖尿病组降低(P=0.000)。结论SD大鼠糖尿病成模8周,可见动脉粥样硬化的早期表现,但未见明显动脉粥样斑块形成;糖尿病大鼠主动脉LOX-1的mRNA和蛋白表达水平增高;替米沙坦可抑制大鼠主动脉LOX-1 mRNA和蛋白的表达。

    Abstract:

    Aim To detect the expression of lectin-like oxidized low-density lipoprotein receptor-1(LOX-1) on aorta in diabetic rats and to observe the effects of telmisartan in order to investigate the mechanisms of marcrovascular disease in diabetes.Methods A total number of 32 male 6 weeks of age Sprague Dawley rats were divided into two groups,including control group(n=8) and experimental group(n=24).The latter group of rats was fed with high fat and sugar diet for 4 weeks and then was made into diabetic model by intraperitoneal injection of streptozotocin once at a dose of 45 mg/kg.The diabetic rats were further divided into diabetic mellitus group(n=9)(DM group),telmisartan group(n=11) which was given 20 mg/kg weight telmisartan,control group and DM group rats received distilled water.All groups of rats were given medicines by using oral gavage for 8 weeks.The serum lipid parameters were determined by routine methods using a fully automatic biochemical analyzer.Aorta paraffin sections were performed HE stain to observe atherosclerotic lesion.Expression of LOX-1 mRNA were detected by real-time PCR and Western blot was used to quantify their protein expression.Results No significant difference was found among three groups on the serum levels of total cholesterol(TC)(P=0.13) and triglyceride(TG)(P=0.35).High density lipoprotein(HDL)(0.99±0.12 mmol/L vs 1.37±0.23 mmol/L) was decreased(P=0.001) and low density lipoprotein(LDL)(0.48±0.08 mmol/L vs 0.34±0.03 mmol/L) was increased(P=0.001) in DM group compared with the control.Histology of rat aorta showed in control group the intima was thin and smooth,endothelial cells lined,while in DM group the intima was thicken in local lesion and it did not attenuate after treatment of telmisartan compared with DM group.No obvious atherosclerotic plaque was found in the three groups.In DM group,LOX-1 mRNA(0.316±0.055 vs 0.154±0.029) and protein expression(1.271±0.238 vs 0.739±0.113) were significantly upregulated compared with the control(P=0.000) while they(0.192±0.030 vs 0.316±0.055 and 0.691±0.198 vs 1.271±0.238) were downregulated in telmisartan group compared with the DM group(P=0.000).Conclusion LOX-1 mRNA and protein expression were increased in aorta of diabetic rats.Telmisartan may downregulate LOX-1 expression in diabetic rats.

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刘谦, 王云, 常志文.替米沙坦对糖尿病大鼠主动脉组织血凝素样氧化型低密度脂蛋白受体1表达的影响[J].中国动脉硬化杂志,2011,19(7):583~588.

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  • 收稿日期:2011-01-27
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