葛根素联用格列齐特对2型糖尿病模型大鼠肾脏纤维化的影响及其机制
发布时间：2019-01-30 18:38
【摘要】：目的:观察葛根素联用格列齐特对2型糖尿病模型大鼠肾脏纤维化的影响，并通过观察肾脏组织中Ang II含量及MCP-1、TGF-β1表达的变化，初步探究其作用机制。 方法:Wistar大鼠64只，随机选择8只为正常对照组，余下大鼠高糖高脂饲养后，采用小剂量腹腔注射35mg·kg-1链脲佐菌素(STZ)诱导糖尿病大鼠模型。将造模成功的大鼠随机分成6组：模型组（生理盐水）、格列齐特组(10mg·kg-1·d-1)、葛根素低、中、高剂量组(40、80、160mg·kg-1·d-1)、葛根素联用格列齐特组(40mg·kg-1·d-1+5mg·kg-1·d-1)，连续给药6周。大鼠麻醉后，腹主动脉取血，检测有关指标；取肾脏，并称重，计算肾脏重量指数。HE染色观察大鼠肾脏病理学改变，Masson染色观察大鼠肾脏胶原纤维变化。用全自动生化仪测定大鼠血清肌酐(Scr)和尿素氮(BUN)水平；放免法测肾脏组织中Ang II含量；Q-RT-PCR检测大鼠肾脏组织MCP-1、TGF-β1mRNA的表达；Western blot检测肾组织MCP-1、TGF-β1蛋白的表达。 结果:①与正常组比较，模型组大鼠体重降低显著(P＜0.01)；与模型组相比，各治疗组大鼠体重降低程度减弱，尤其葛根素联用格列齐特组更为显著（P＜0.01）。②与正常组相比，模型组大鼠血糖、血肌酐、尿素氮水平显著升高(P＜0.01)；与模型组相比，各治疗组大鼠血糖、血肌酐、尿素氮明显降低，葛根素联用格列齐特作用更为明显(P＜0.01)。③与正常组相比，模型组大鼠肾组织AngⅡ含量、TGF-β1与MCP-1mRNA和蛋白表达明显升高；与模型组相比，各剂量组能不同程度降低肾组织AngⅡ含量(P＜0.01或P＜0.05)；除葛根素低剂量组外，其他给药组均能降低肾脏TGF-β1与MCP-1mRNA和蛋白表达，其中，联合用药效果最明显(P＜0.01)。④与正常组比较，模型组大鼠肾小球增大，肾小囊变窄，系膜基质增多，肾小管结构混乱；与模型组相比，各治疗组大鼠肾脏病理损伤得到不同程度的改善，肾脏胶原沉积显著改善，其中联用组效果最好(P＜0.01)。 结论:葛根素联用格列齐特能显著改善糖尿病大鼠肾脏纤维化及胶原沉积，，其机制与两药合用降低糖尿病大鼠的血糖，降低肾脏AngⅡ含量，抑制肾脏TGF-β1与MCP-1mRNA及蛋白的表达有关。
[Abstract]:Aim: to observe the effect of puerarin combined with gliclazide on renal fibrosis in rats with type 2 diabetes mellitus, and to explore its mechanism by observing the content of Ang II and the expression of MCP-1,TGF- 尾 1 in renal tissue. Methods: Sixty-four Wistar rats were randomly selected as normal control group. The diabetic rats were induced by intraperitoneal injection of 35mg kg-1 streptozotocin (STZ) with low dose of 35mg kg-1 streptozotocin (STZ). The successful rats were randomly divided into 6 groups: model group (normal saline), gliclazide group (10mg kg-1 d-1), low, medium and high dose puerarin group (40,80160 mg kg-1 d-1). Puerarin combined with gliclazide group (40mg kg-1 d-1 5mg kg-1 d-1) was administered continuously for 6 weeks. After anesthesia, blood was taken from abdominal aorta, kidney was taken and weighed, kidney weight index was calculated. Pathological changes of rat kidney were observed by HE staining and collagen fibers were observed by Masson staining. The levels of serum creatinine (Scr) and urea nitrogen (BUN) were measured by automatic biochemical instrument, the content of Ang II in renal tissue was measured by radioimmunoassay, the expression of MCP-1,TGF- 尾 1mRNA in renal tissue was detected by Q-RT-PCR. The expression of MCP-1,TGF- 尾 1 protein in renal tissue was detected by Western blot. Results: 1 compared with the normal group, the weight of the model group decreased significantly (P < 0.01); Compared with the model group, the weight loss was decreased in each treatment group, especially in the puerarin combined with gliclazide group (P < 0.01). 2 compared with the normal group, the blood glucose and creatinine in the model group were significantly lower than those in the control group. Urea nitrogen level increased significantly (P < 0.01). Compared with the model group, blood glucose, serum creatinine and urea nitrogen were significantly decreased in each treatment group, and the effects of puerarin combined with gliclazide were more obvious (P < 0. 01). 3 compared with the normal group, the content of Ang 鈪
本文编号：2418392
[Abstract]:Aim: to observe the effect of puerarin combined with gliclazide on renal fibrosis in rats with type 2 diabetes mellitus, and to explore its mechanism by observing the content of Ang II and the expression of MCP-1,TGF- 尾 1 in renal tissue. Methods: Sixty-four Wistar rats were randomly selected as normal control group. The diabetic rats were induced by intraperitoneal injection of 35mg kg-1 streptozotocin (STZ) with low dose of 35mg kg-1 streptozotocin (STZ). The successful rats were randomly divided into 6 groups: model group (normal saline), gliclazide group (10mg kg-1 d-1), low, medium and high dose puerarin group (40,80160 mg kg-1 d-1). Puerarin combined with gliclazide group (40mg kg-1 d-1 5mg kg-1 d-1) was administered continuously for 6 weeks. After anesthesia, blood was taken from abdominal aorta, kidney was taken and weighed, kidney weight index was calculated. Pathological changes of rat kidney were observed by HE staining and collagen fibers were observed by Masson staining. The levels of serum creatinine (Scr) and urea nitrogen (BUN) were measured by automatic biochemical instrument, the content of Ang II in renal tissue was measured by radioimmunoassay, the expression of MCP-1,TGF- 尾 1mRNA in renal tissue was detected by Q-RT-PCR. The expression of MCP-1,TGF- 尾 1 protein in renal tissue was detected by Western blot. Results: 1 compared with the normal group, the weight of the model group decreased significantly (P < 0.01); Compared with the model group, the weight loss was decreased in each treatment group, especially in the puerarin combined with gliclazide group (P < 0.01). 2 compared with the normal group, the blood glucose and creatinine in the model group were significantly lower than those in the control group. Urea nitrogen level increased significantly (P < 0.01). Compared with the model group, blood glucose, serum creatinine and urea nitrogen were significantly decreased in each treatment group, and the effects of puerarin combined with gliclazide were more obvious (P < 0. 01). 3 compared with the normal group, the content of Ang 鈪
本文编号：2418392
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