摘要
目的研究钠-葡萄糖协同转运蛋白(sodium-dependent glucose transporters,SGLT) 2抑制剂达格列净对糖尿病肾病(diabetic nephropathy,DN)大鼠的肾功能、足细胞损伤及10号染色体同源丢失性磷酸酶-张力蛋白基因(phosphase and tensin homology deleted on chromosome ten,PTEN)/磷酸酰肌醇3激酶/蛋白激酶B(phosphoinositide 3 kinese/protein kinase B, PI3K/Akt)信号通路的影响。方法 36只SD大鼠被随机分为对照组、模型组和实验组,每组12只;其中模型组和实验组腹腔注射链尿佐菌素进行DN造模,对照组注射等量生理盐水;造模成功后实验组1 mg/(kg·d)达格列净灌胃,对照组和模型组灌胃等量生理盐水,连续灌胃8周。比较各组给药前和给药8周后空腹血糖,计算肾脏指数,测量血清肌酐(Scr)、尿素氮(BUN),在光学显微镜下观察肾组织HE染色结果,在电子显微镜下观察足细胞形态,采用Western blot检测肾脏组织中PTEN、磷酸化PI3K(p-PI3K)、磷酸化Akt(p-Akt)蛋白相对表达。结果给药前,模型组和实验组空腹血糖差异无统计学意义(P>0.05),但显著高于对照组(P<0.05);8周后空腹血糖、血清Scr、血清BUN、肾脏指数、24 h尿蛋白排泄率:模型组>实验组>对照组,组间两两比较,差异均有统计学意义(P<0.05)。光学显微镜下HE染色结果:实验组大鼠基质增生增厚、基底膜增厚、系膜扩张,但程度低于模型组高于对照组;电子显微镜下对照组足细胞形态正常,实验组足细胞可见部分足突融合,排列较模型组整齐,模型组可见显著足突融合、排列混乱、嵴断裂。Western blot结果表明p-PI3K、p-Akt蛋白表达:模型组>实验组>对照组,组间比较差异均有统计学意义(P<0.05),PTEN蛋白表达:模型组<实验组<对照组,组间比较差异均有统计学意义(P<0.05)。结论达格列净能降低DN大鼠的血糖水平,减少尿蛋白,改善肾功能,减轻足细胞损伤,可能与其上调PTEN蛋白、下调p-PI3K/p-Akt表达有关。
Objective To study the effect of sodium-dependent glucose transporters(SGLT)-2 inhibitor(dapagliflozin) on podocyte injury and phosphase and tensin homology deleted on chromosome ten(PTEN)-phosphoinositide 3 kinese/protein kinase B(PI3 K/Akt) signaling pathway in diabetic nephropathy rats. Methods Thirty-six SD rats were randomly divided into control group, model group and observation group with 12 rats in each group. The model group and observation group recieved intraperitoneal injection of streptozotocin to establish DN model, and the control group was injected with placebo saline. The observation group was intragastrically administered with 1 mg/(kg·d) dapagliflozin every day, while the control group and the model group were intragastrically administered with the same amount of saline for 8 weeks.The fasting blood glucose was compared before and 8 weeks after administration.The renal index was calculated, the serum Scr and BUN were measured. The HE staining results of kidney tissue were observed under light microscope, the podocyte morphology were observed under electron microscope.The relative expression of PTEN, phosphorylated PI3 K(p-PI3 K), and phosphorylated Akt(p-Akt)protein expression in kidney tissue were detected by Western blot. Results Before intervention, there was no significant difference of fasting blood glucose between model group and observation group(P>0.05), but it was significantly higher than that of control group(P<0.05). After 8 weeks, fasting blood glucose, serum Scr, serum BUN, kidney index, 24-hour urinary protein excretion rate were significantly highest in model group, and followed by experimental group and control group(P<0.05).The results of HE staining under optical microscope showed that the matrix hyperplasia, basement membrane thickening and mesangial dilatation in the observation group were lower than those in the model group, but higher than those in the control group.Under electron microscopy, the podocytes in the control group were normal in shape. In the observation gro
作者
祝再然
张明
赵桂金
董嘉良
ZHU Zai-ran;ZHANG Ming;ZHAO Gui-jin;DONG Jia-liang(Department of Endocrinology,Tianjin Ninghe District Hospital,Tianjin 301500,China)
出处
《广东医学》
CAS
2020年第24期2490-2494,共5页
Guangdong Medical Journal
基金
天津自然科学基金项目(17JCZDJC35000)。
