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目的:观察黄芪六一汤对糖尿病大鼠血糖、糖化血红蛋白、血脂及肾小管上皮钠-葡萄糖共转运蛋白2(SGLT2)的作用,探讨该方治疗糖尿病的疗效及其可能的作用机制。方法:将77只SPF级SD大鼠按体重随机分为6组,分别为正常组,模型组,二甲双胍组(0.15 g·kg~(-1)),黄芪六一汤低、中、高剂量组(3.15,6.30,12.60 g·kg~(-1));糖尿病模型复制方法采用高脂高糖喂养28 d后,40 mg·kg~(-1)体重剂量链脲佐菌素(STZ)腹腔注射造模。STZ注射后第7天开始分别给予相应治疗药物灌胃,正常组、模型组同法灌胃相应体积的水。连续灌胃给药治疗6周,每周1次,禁食6 h后尾静脉取血测血糖,末次给药后禁食12 h后,给大鼠进行尾静脉取血测血糖,然后麻醉大鼠,腹腔静脉取血,处死动物后留取取肾、胰腺做病理切片苏木素-伊红(HE)染色检查。观察血糖、糖化血红蛋白、血脂四项、体重、进食量、肾组织SGLT2蛋白表达等指标。结果:各造模组的血糖均高于正常组(P<0.01),血糖>13.0 mmol·L~(-1)。经过6周自行恢复后,模型组血糖仍显著高于正常组(P<0.01);二甲双胍组、黄芪六一汤中、高剂量组血糖均明显低于模型组(P<0.05)。模型组的糖化血红蛋白升高,高于正常组(P<0.01),与模型组比较,二甲双胍、黄芪六一汤高剂量组糖化血红蛋白明显低于模型组(P<0.05)。造模组大鼠胰腺病理切片HE染色可见胰岛结构完整,说明本实验中并未造成胰岛的完全破坏。肾脏病理切片可见,各组大鼠肾脏肾小球、集合小管、近端及远端小管的结构完整,未见明显病理损害。各给药组大鼠肾组织SGLT2蛋白表达均有所降低(P<0.05,P<0.01)。结论:高糖高脂饮食合并腹腔注射STZ致糖尿病大鼠模型肾组织SGLT2蛋白表达增高,黄芪六一汤能降低实验性糖尿病模型大鼠血糖、糖化血红蛋白,有降低模型大鼠肾组织中SGLT2蛋白表达的作用。部分抑制肾小管上皮葡萄糖重吸收可能是黄芪六一汤治疗糖尿病的作用之一。
Objective: To observe the effect of Astragalus and Liuyi Decoction on blood glucose, glycosylated hemoglobin, blood lipid and renal tubular epithelial sodium-glucose cotransporter 2 (SGLT2) in diabetic rats, and to explore its curative effect and its possible mechanism. Methods: 77 SPF SD rats were randomly divided into 6 groups according to body weight: normal group, model group, metformin group (0.15 g · kg -1), low, medium and high dose of Huangqi Liuyi decoction (3.15,6.30,12.60 g · kg -1); diabetic model replication method After high-fat and high-glucose fed for 28 days, 40 mg · kg -1 body weight of streptozotocin (STZ) Abdominal injection modeling. After 7 days of STZ injection, the corresponding therapeutic drugs were given to gavage respectively. Normal group and model group were given the same volume of water by the same method. After continuous gavage for 6 weeks, once a week, blood was collected from the tail vein 6 hours after fasting. After 12 h of fasting, rats were sacrificed for tail blood to measure blood glucose, then anesthetized Rat, abdominal venous blood, after the animals were sacrificed to take the kidney, the pancreas do pathological sections hematoxylin-eosin (HE) staining. Observed blood glucose, glycosylated hemoglobin, blood lipids, weight, food intake, kidney SGLT2 protein expression and other indicators. Results: The blood glucose of each model group was higher than that of the normal group (P <0.01) and the blood glucose> 13.0 mmol·L -1. After six weeks of self-recovery, the blood glucose in the model group was still significantly higher than that in the normal group (P <0.01). The levels of blood glucose in the middle-dose and high-dose groups of metformin and Huangqi Liuyi Decoction were significantly lower than those of the model group (P <0.05). The levels of HbA1c in model group were significantly higher than those in normal group (P <0.01). Compared with model group, the levels of HbA1c in metformin and Huangqi Liuyi decoction group were significantly lower than those in model group (P <0.05). Pathological sections of rat model of pancreatic tissue HE staining shows complete islet structure, indicating that in this experiment did not cause complete destruction of islets. Renal pathological section shows that the rats kidney glomeruli, collecting tubules, proximal and distal tubule structure is complete, no obvious pathological damage. The expression of SGLT2 protein in renal tissue of rats in each administration group was decreased (P <0.05, P <0.01). CONCLUSION: SGLT2 protein expression is increased in high-sugar and high-fat diet combined with STZ-induced diabetic rat kidney model. Astragalus and Liuyi Decoction can reduce blood glucose and HbA1c in experimental diabetic rats, and reduce the expression of SGLT2 protein The role of expression. Partial inhibition of renal tubular epithelial glucose reabsorption may be one of the role of Astragalus Liuyi Decoction in the treatment of diabetes.