氯沙坦对糖尿病大鼠胰岛组织中转化生长因子-β1、Smad7蛋白表达的影响

摘要

目的：探讨血管紧张素Ⅱ﹙AngⅡ﹚受体阻滞剂氯沙坦对糖尿病大鼠胰岛组织中转化生长因子﹙TGF﹚-β1及smad7表达的影响。方法选取90只健康成年Wistar大鼠作为本组实验的观察对象,随机将其分为健康组﹑糖尿病组及糖尿病氯沙坦组各30只,健康组采用普通饲料喂养方式,糖尿病组与糖尿病氯沙坦组采用高脂﹑高热量饲料喂养方式,喂养8周后糖尿病组和糖尿病氯沙坦组分别注射链脲佐菌素﹙STZ﹚诱导糖尿病大鼠模型,造模成功后,给予糖尿病氯沙坦组大鼠氯沙坦30 mg/﹙kg•d﹚灌胃治疗,并于8周后对比各组大鼠的体质量﹑血糖﹑血胰岛素及TGF-β1及Smad7蛋白的表达变化。结果①糖尿病组与糖尿病氯沙坦组的血糖水平分别为﹙19.3±2.7﹚mmol/L与﹙13.1±1.6﹚mmol/L,均明显高于健康组,血胰岛素及体质量均低于健康组,差异有统计学意义﹙P<0.05﹚。②糖尿病对照组与糖尿病氯沙坦组胰岛组织中的TGF-β1含量分别为﹙0.41±0.11﹚与﹙0.15±0.09﹚mmol/L,均有所增加；Smad7蛋白含量分别为﹙0.23±0.08﹚与﹙0.36±0.11﹚,均有所降低,糖尿病氯沙坦组的各项指标均有明显改善,优于糖尿病对照组,差异有统计学意义﹙P<0.05﹚。结论AngⅡ受体阻滞剂氯沙坦可以降低胰腺组织中TGF-β1蛋白的表达,减少TGF-β1及Smad7蛋白在尿液中的排泄,抑制糖尿病大鼠胰岛组织纤维化,从而起到保护肾脏的作用。%Objective To study the effects of angiotensin II (Ang II) receptor blocker losartan on the expression of transforming growth factor beta 1 (TGF-β1) and Smad7 protein in the pancreatic tissue of diabetic rats. Methods 90 healthy adult Wistar rats were selected as the object of observation of this experiment, and they were randomly divided into healthy group, diabetic group and diabetes losartan group with 30 rats in each. The healthy group was treated with normal feed, the diabetic group and diabetes losartan group were treated with the high fat and calorie feed. 8 weeks after feeding, the diabetic group and diabetes losartan group were injected with streptozotocin (STZ) for induction of diabetic rats model. After the success of modeling, the rats in the diabetes losartan group were given intragastric administration of losartan 30 mg/kg/d. And 8 weeks later, the changes in body weight, blood glucose, blood insulin and expression of TGF-β1 and Smad7 protein were compared between the groups. Results (1) The blood glucose of the diabetic group and the diabetes losartan group was (19.3±2.7) mmol/L, (13.1±1.6) mmol/L, respectively, significantly higher than that of the healthy group, respectively, while the blood insulin and body weight were lower than those of the healthy group, P<0.05. (2) The TGF-beta 1 content in the diabetic control group and the diabetes losartan group was (0.41±0.11) mmol/L, (0.15 ±0.09) mmol/L, respectively, all increased; Smad7 protein content was (0.23 ±0.08) and (0.36 ±0.11), respectively, all de_creased, the indicators in the diabetes losartan group improved significantly, better than the diabetic control group with statistical significance, P<0.05. Conclusion Ang II receptor blocker losartan can reduce the expression of TGF-beta 1 protein in pancreatic tissue, decrease the excretion of TGF-beta 1 and Smad7 protein in the urine, inhibit the fibrosis of pancreatic islet tissue of dia_betic rats, thus it can protect the kidney.