Xu Yun, Chen Xue-Hui, Bai Li-Wei, Yin Qing-Feng, Feng Chun-Yu, Zhang Qing-Gui
The Department ofEndocrinology, Ward 1, the First Affiliated Hospital of Xinxiang Medical University, Weihui 453100.
Internal Medicine,Ward 3, the People's Hospital of Wei Hui, Weihui 453100, China.
Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2020 Nov;36(6):565-570. doi: 10.12047/j.cjap.6001.2020.119.
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. 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. Compared with group A, the body weight, SOD, GSH-Px levels of rats in each group were significantly decreased (＜0.05), while the levels of FBG, HbA1c, BUN, SCR and MDA were significantly increased (＜0.05), renal pathological damage was serious, the relative expressions of GLUT2, GLUT4 mRNA and protein in renal tissue were significantly decreased (＜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 (＜0.05), while the levels of FBG, HbA1c, BUN, SCR and MDA were significantly decreased (＜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 ＜0.05). Dapagliflozin can alleviate the condition of type 2 diabetic rats and up regulate the expression of GLUT2 and GLUT4 genes in kidney.
探讨达格列净对2型糖尿病大鼠葡萄糖转运蛋白2（GLUT2）和葡萄糖转运蛋白4（GLUT4）基因表达的影响。采用高脂饮食联合40mg/kg链脲佐菌素（STZ）建立2型糖尿病大鼠模型。当空腹血糖（FBG）含量≥16.7mmol/L时，模型建立成功。造模成功后，将大鼠随机分为模型组（B组，生理盐水）、达格列净低剂量组（C组，0.75mg/kg）、达格列净中剂量组（D组，1.5mg/kg）和达格列净高剂量组（E组，3.0mg/kg），每组6只。选取6只健康SD大鼠作为正常对照组（A组，生理盐水）。各组均每日灌胃给药1次，连续7周。7周后测量体重、血清FBG、糖化血红蛋白（HbA1c）、血尿素氮（BUN）和血清肌酐（Scr）。采用酶联免疫吸附测定（ELISA）法检测血清及肾脏中丙二醛（MDA）、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-PX）水平。采用HE染色观察肾脏病理变化。采用蛋白质印迹法检测GLUT2和GLUT4的蛋白表达。采用RT-qPCR法检测肾脏组织中GLUT2和GLUT4 mRNA的相对表达。与A组比较，各组大鼠体重、SOD、GSH-Px水平显著降低（＜0.05），而FBG、HbA1c、BUN、SCR及MDA水平显著升高（＜0.05），肾脏病理损伤严重，肾脏组织中GLUT2、GLUT4 mRNA及蛋白的相对表达显著降低（＜0.05）。与B组比较，C组、D组和E组大鼠体重、SOD、GSH-Px水平及GLUT2和GLUT4的mRNA相对表达显著升高（＜0.05），而FBG、HbA1c、BUN、SCR及MDA水平显著降低（＜0.05）。D组和E组肾脏病理损伤明显减轻，肾脏组织中GLUT2和GLUT4蛋白表达显著增加（均＜0.05）。达格列净可改善2型糖尿病大鼠病情，并上调肾脏中GLUT2和GLUT4基因的表达。
