论文部分内容阅读
目的研究通络方剂对链脲佐菌素(STZ)诱导的1型糖尿病大鼠肾脏组织ERK1/2信号转导通路的影响及对肾脏的保护机制。方法健康SD大鼠随机分为正常组(10只)和造模组。造模组给予单次腹腔注射STZ 60mg/kg,造模成功后按体质量随机分为5组:糖尿病非治疗组,通络方剂低剂量组[0.5g/(kg.d)]、中剂量组[1.0g/(kg.d)]、高剂量组[2.0g/(kg.d)]和氯沙坦组[30mg/(kg.d)],每组10只。适应性饲养1周后,按分组分别给予不同处理,持续给药12周后处死,称体质量,取血检测血糖、血脂、血肌酐、尿素氮,留24h尿检测尿肌酐、尿蛋白、尿微量白蛋白,ELISA法检测血清及肾脏组织中血管紧张素Ⅱ(AngⅡ)的含量,取左肾称质量,H-E、PAS染色观察肾脏病理改变,免疫组织化学法检测p-ERK1/2蛋白的表达,蛋白质印迹法检测VEGF蛋白的表达。结果与糖尿病非治疗组比较,糖尿病大鼠系膜细胞增殖受到抑制,蛋白尿明显降低,体质量增加,肾肥大指数降低,肌酐清除率、血尿素氮降低,肾功能改善,血清及肾组织AngⅡ含量降低,VEGF及p-ERK1/2蛋白的表达降低(P<0.05)。中剂量通络方剂与氯沙坦在改善糖尿病大鼠肾功能及抑制AngⅡ、VEGF、p-ERK1/2表达方面差异无统计学意义。结论通络方剂对糖尿病大鼠肾脏的保护作用可能与抑制AngⅡ、VEGF表达,阻断ERK1/2信号转导通路有关。
Objective To study the effect of Tongluo Recipe on ERK1 / 2 signal transduction pathway in kidneys of streptozotocin (STZ) -induced type 1 diabetic rats and its protective mechanism on kidney. Methods Healthy SD rats were randomly divided into normal group (n = 10) and model group. The model rats were given a single intraperitoneal injection of STZ 60mg / kg, and were divided into 5 groups randomly according to the body weight after the model was established: diabetes mellitus group, Tongluo Recipe low dose group [0.5g / (kg · d)], Group [1.0g / (kg · d)], high dose group [2.0g / (kg · d)] and losartan group [30mg / (kg · d)]. After 1 week of adaptive feeding, different groups were given different treatments and were sacrificed 12 weeks after the continuous administration. The body weight was measured and blood glucose, blood lipids, serum creatinine and urea nitrogen were measured. Urinary creatinine, urinary protein, The content of angiotensin Ⅱ (AngⅡ) in serum and kidney tissue was detected by ELISA and the quality of the left kidney was weighed. The pathological changes of kidney were observed by HE and PAS staining. The expression of p-ERK1 / 2 protein was detected by immunohistochemistry Western blotting was used to detect the expression of VEGF protein. Results Compared with untreated diabetic group, the proliferation of mesangial cells in diabetic rats was inhibited, proteinuria was significantly decreased, body weight was increased, renal hypertrophy index was decreased, creatinine clearance rate, blood urea nitrogen decreased, renal function improved, serum and renal Ang Ⅱ The content of VEGF and p-ERK1 / 2 protein decreased (P <0.05). There was no significant difference in the effects of middle-dose Tongluo Recipe and Losartan on the improvement of renal function and the expression of AngⅡ, VEGF and p-ERK1 / 2 in diabetic rats. Conclusion The protective effect of Tongluo Recipe on the kidney of diabetic rats may be related to inhibiting the expression of AngⅡ and VEGF and blocking the ERK1 / 2 signal transduction pathway.