首页|黄芪六一汤对2型糖尿病模型大鼠肾小管上皮葡萄糖重吸收的作用

黄芪六一汤对2型糖尿病模型大鼠肾小管上皮葡萄糖重吸收的作用

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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6h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.
Effect of Huangqi Liuyi Tang on Glucose Re-absorption Via Renal Tubular Epithelial Cells in Type 2 Diabetes Model Rats
Objective:To observe the effect of Huangqi Liuyi Tang on diabetic rats' blood glucose,glycosylated hemoglobin,blood lipid and the renal tubular epithelial reabsorption of glucose transporter 2 (SGLT2),and explore its efficacy and possible mechanismt in the treatment of diabetes.Method:The 77 SPF rats were randomly divided into 6 groups by weight:normal control group,model group,metformin group (0.15 g·kg-1),Huangqi Liuyi Tang low,middle and high dose groups (3.15,6.30,12.60 g·kg-1).Diabetes models were established by using high fat and high glucose diet for 28 days and then with intraperitoneal injection of streptozotocin at the dose of 40 mg·kg-1 body weight.7 days after STZ injection,corresponding drugs were given by gavage.Equivalent volume of water was given in the normal control group and model control group by the same method.Gavage medication lasted for six weeks,once a week.Venous blood from the tails was collected to measure blood glycose after 6-hour fasting;after fasting 12-hour at the last time of gavage,the venous blood from the tails was taken for blood glycose and then the rats were anaesthetized to collect the abdominal venous blood.The kidney and pancreas were taken for histopathological examination after the rats were sacrificed.The blood glucose,glycosylated hemoglobin,blood lipid,body weight,food intake,and the expression of renal tissue SGLT2 were observed.Result:The blood glucose levels in modeling groups were higher than those in normal control group (P <0.01),with a blood glucose value > 13.0 mmol · L-1.After six weeks self-healing,the blood glucose level in model group was still significantly higher than that of normal control group (P < 0.01);the blood glucose levels in metformin group,Huangqi Liuyi Tang in middle and high dose groups were lower than that in model group (P < 0.05).Glycosylated hemoglobin level was increased in model group and higher than that in the normal control group (P < 0.01).As compared with the model group,glycosylated hemoglobin level was decreased in metformin group and the Huangqi Liuyi Tang high dose group (P < 0.05).In the pancreas pathological HE staining in model rats,complete pancreas islet structure was seen,indicating that islet was not destroyed completely in this experiment.Renal pathological slices showed that the structures of renal glomerulus,collections,tubular,proximal and distal tubule were complete in all groups,with no obvious pathological damages.After treatment,SGLT2 protein expression levels were reduced in various treatment groups (P < 0.05,P < 0.01).Conclusion:High sugar and high fat diet with intraperitoneal injection of STZ increased SGLT2 protein expression in kidney tissues of diabetic models.Huangqi Liuyi Tang can reduce blood glucose,glycosylated hemoglobin,and lower SGLT2 protein expression in diabetes model rats.Its treatment efficacy for diabetes may be associated with partial inhibition of renal tubular epithelial reabsorption of glucose.

diabetesHuangqi Liuyi Tangblood glucoseglycosylated hemoglobinsodium-glucose transport protein-2 (SGLT2)

许燕玲、郑媛嘉、李振、温丽敏、郭文峰

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广州中医药大学脾胃研究所,广州 510405

糖尿病 黄芪六一汤 血糖 糖化血红蛋白 钠-葡萄糖共转运蛋白2

国家自然科学基金面上项目

81072753

2017

中国实验方剂学杂志
中国中医科学院中药研究所 中国中西医结合学会中药专业委员会

中国实验方剂学杂志

CSTPCDCSCD北大核心
影响因子:1.62
ISSN:1005-9903
年,卷(期):2017.23(11)
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