达格列净对2型糖尿病大鼠肾脏葡萄糖转运蛋白2及葡萄糖转运蛋白4基因表达的影响*

doi:10.12047/j.cjap.6001.2020.119

中国应用生理学杂志 ›› 2020, Vol. 36 ›› Issue (6): 565-570.doi: 10.12047/j.cjap.6001.2020.119

达格列净对2型糖尿病大鼠肾脏葡萄糖转运蛋白2及葡萄糖转运蛋白4基因表达的影响^*

徐云¹, 陈雪辉¹, 白立炜¹, 尹清风¹, 冯春瑜², 张清贵^1△

1.新乡医学院第一附属医院内分泌科一病区, 河南卫辉 453100;
2.卫辉市人民医院内科, 河南卫辉 453100

收稿日期:2020-02-24 修回日期:2020-11-12 出版日期:2020-11-28 发布日期:2021-03-15
通讯作者: ^△Tel: 13839095631; E-mail: 1090649251@qq.com
基金资助:
^*河南省新乡医学院第一附属医院青年培育基金项目(QN-2017-B027)

Effect of dapagliflozin on gene expression of glucose transporter 2 and glucose transporter 4 in kidney of type 2 diabetic rats

XU Yun¹, CHEN Xue-hui¹, BAI Li-wei¹, YIN Qing-feng¹, FENG Chun-yu², ZHANG Qing-gui^1△

1. The Department ofEndocrinology, Ward 1, the First Affiliated Hospital of Xinxiang Medical University, Weihui 453100;
2. Internal Medicine,Ward 3, the People's Hospital of Wei Hui, Weihui 453100, China

Received:2020-02-24 Revised:2020-11-12 Online:2020-11-28 Published:2021-03-15

摘要/Abstract

摘要： 目的:探讨达格列净对2型糖尿病大鼠肾脏葡萄糖转运蛋白2(GLUT2)和葡萄糖转运蛋白4(GLUT4)基因表达的影响。方法:使用高脂饲料和一次性注射40 mg/kg链脲佐菌素(STZ)建立2型糖尿病大鼠模型,造模大鼠以空腹血糖(FBG)含量≥16.7 mmol/L时视为造模成功。造模成功后随机分为模型组(B组,生理盐水)、达格列净低剂量组(C组,0.75 mg/kg)、达格列净中剂量组(D组,1.5 mg/kg)、达格列净高剂量组(E组,3.0 mg/kg),每组6只;另选取6只健康的SD大鼠作为正常对照组(A组,生理盐水)。各组均为灌胃给药,每天1次,连续7周。灌胃给药7周后测定大鼠的体重以及血清FBG、糖化血红蛋白(HbA1c)、血尿素氮(BUN)、血肌酐(Scr)的变化;采用酶联免疫吸附测定血清及肾组织丙二醛(MDA)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px);采用HE观察肾脏病理学变化;采用Western blot检测肾脏组织中GLUT2、GLUT4蛋白表达;RT-qPCR检测肾脏组织中GLUT2、GLUT4 mRNA相对表达量。结果: 与A组比较,各组大鼠的体重及SOD、GSH-PX水平明显降低(P＜ 0.05),FBG、HbA1c、BUN、Scr、MDA水平明显升高(P＜0.05),肾脏病理损伤严重,肾组织GLUT2、GLUT4 mRNA相对表达量和蛋白表达均明显降低(P均＜0.05)。与B组比较,C组、D组和E组大鼠的体重、SOD、GSH-PX水平和肾组织GLUT2、GLUT4 mRNA相对表达量明显升高(P＜0.05),FBG、HbA1c、BUN、Scr、MDA水平明显降低(P＜ 0.05);D组和E组肾脏病理损伤明显减轻,肾组织GLUT2、GLUT4蛋白表达均明显升高(P均＜0.05)。结论:达格列净可缓解2型糖尿病模型大鼠的病情,并上调肾脏GLUT2及GLUT4基因的表达。

关键词: 达格列净, 2型糖尿病, 大鼠, 葡萄糖转运蛋白2, 葡萄糖转运蛋白4

Abstract: Objective: To investigate the effects of dapagliflozin on the gene expressions of glucose transporter 2 (GLUT2) and glucose transporter 4 (GLUT4) in type 2 diabetic rats. Methods: High fat diet and 40 mg/kg streptozotocin (STZ) were used to establish the rat model of type 2 diabetes mellitus. When the fasting blood glucose (FBG) content was more than or equal to 16.7 mmol/L, the model was established successfully. After successful modeling, the rats were randomly divided into model group (group B, normal saline), dapagliflozin low-dose group (Group C, 0.75 mg/kg), dapagliflozin middle dose group (Group D, 1.5 mg/kg) and dapagliflozin high-dose group (Group E, 3.0 mg/kg), with 6 rats in each group. Six healthy SD rats were selected as normal control group (group A, normal saline). Each group was administrated by gavage once a day for 7 weeks. The body weight, serum FBG, hemoglobin A1c (HbA1c), blood urea nitrogen (BUN) and serum creatinine (Scr) were measured after 7 weeks. The levels of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) in serum and kidney were measured by enzyme-linked immunosorbent assay (ELISA). HE staining was used to observe the pathological changes of kidney. The protein expressions of GLUT2 and GLUT4 were detected by Western blot. RT-qPCR was used to detect the relative expressions of GLUT2 and GLUT4 mRNA in kidney tissue. Results: Compared with group A, the body weight, SOD, GSH-Px levels of rats in each group were significantly decreased (P＜0.05), while the levels of FBG, HbA1c, BUN, SCR and MDA were significantly increased (P＜0.05), renal pathological damage was serious, the relative expressions of GLUT2, GLUT4 mRNA and protein in renal tissue were significantly decreased (P＜0.05). Compared with group B, the body weight, SOD, GSH-Px levels and the mRNA relative expressions of GLUT2 and GLUT4 in group C, group D and group E were significantly increased (P＜0.05), while the levels of FBG, HbA1c, BUN, SCR and MDA were significantly decreased (P＜0.05). The renal pathological damage in group D and group E was significantly alleviated, and the expressions of GLUT2 and GLUT4 protein in renal tissue were significantly increased (all P＜0.05). Conclusion: Dapagliflozin can alleviate the condition of type 2 diabetic rats and up regulate the expression of GLUT2 and GLUT4 genes in kidney.

Key words: dapagliflozin, type 2 diabetes mellitus, rats, GLUT2, GLUT4

中图分类号:

徐云, 陈雪辉, 白立炜, 尹清风, 冯春瑜, 张清贵. 达格列净对2型糖尿病大鼠肾脏葡萄糖转运蛋白2及葡萄糖转运蛋白4基因表达的影响^*[J]. 中国应用生理学杂志, 2020, 36(6): 565-570.

XU Yun, CHEN Xue-hui, BAI Li-wei, YIN Qing-feng, FENG Chun-yu, ZHANG Qing-gui. Effect of dapagliflozin on gene expression of glucose transporter 2 and glucose transporter 4 in kidney of type 2 diabetic rats[J]. CJAP, 2020, 36(6): 565-570.

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达格列净对2型糖尿病大鼠肾脏葡萄糖转运蛋白2及葡萄糖转运蛋白4基因表达的影响^*

Effect of dapagliflozin on gene expression of glucose transporter 2 and glucose transporter 4 in kidney of type 2 diabetic rats

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