达格列净联用厄贝沙坦对糖尿病大鼠糖代谢及足细胞功能的影响  

Effects of dapagliflozin combined with irbesartan on glucose metabolism and podocyte function in diabetic rats

作　　者：张洁[1] 贾新菊[1] 董闪闪[1] 周慧敏[1] 刘莉 ZHANG Jie;JIA Xin-ju;DONG Shan-shan;ZHOU Hui-min;LIU Li(Department of Endocrinology,The First Hospital of Hebei Medical University,Shijiazhuang 050031,Hebei Province,China)

机构地区：[1]河北医科大学第一医院内分泌科,河北石家庄050031

出　　处：《中国临床药理学杂志》2023年第3期377-381,共5页The Chinese Journal of Clinical Pharmacology

基　　金：河北省医学科研研究课题计划基金资助项目(20221381)。

摘　　要：目的 研究达格列净联用厄贝沙坦对糖尿病大鼠糖代谢及足细胞功能的影响,并探讨相关机制。方法 以腹腔注射链脲佐菌素(STZ)的方法建立大鼠糖尿病模型。将造模成功的40只大鼠随机分为模型组、达格列净组、厄贝沙坦组和联合组,每组10只;另选10只正常大鼠作为对照组。达格列净组腹腔注射2 mg·kg^(-1)达格列净,厄贝沙坦组腹腔注射30 mg·kg^(-1)厄贝沙坦,联合组腹腔注射2 mg·kg^(-1)达格列净+30 mg·kg^(-1)厄贝沙坦,模型组、对照组腹腔注射等体积0.9%NaCl。5组大鼠每天给药1次,连续干预12周。用葡萄糖氧化酶偶联比色法、放射免疫分析法检测糖代谢指标,用硫代巴比妥酸法检测肾组织丙二醛(MDA)含量,用免疫细胞化学染色法检测肾足细胞裂孔隔膜蛋白分子蛋白表达,用蛋白质印迹法检测肾组织烟酰胺腺嘌呤二核苷酸磷酸氧化酶4(NOX4)蛋白表达。结果 对照组、模型组、达格列净组、厄贝沙坦组和联合组的空腹血糖(FBG)分别为(5.23±0.68),(21.46±3.23),(11.49±2.61),(11.78±2.33)和(7.05±0.82)mmol·L^(-1);肾组织MDA含量分别为(41.69±5.97),(115.20±19.65),(90.31±10.56),(89.67±11.31)和(65.87±7.49)nmol·mg^(-1);足细胞裂孔隔膜蛋白分子表达水平分别为1.52±0.36,0.41±0.05,0.70±0.08,0.73±0.09和0.98±0.15;肾组织NOX4蛋白相对表达水平分别为0.41±0.06,0.90±0.11,0.71±0.09,0.73±0.08和0.52±0.06。模型组的上述指标与对照组、达格列净组、厄贝沙坦组比较,联合组的上述指标与达格列净组、厄贝沙坦组比较,差异均有统计学意义(均P<0.05)。结论 达格列净联用厄贝沙坦可改善糖尿病大鼠糖代谢及足细胞功能,减轻肾组织氧化应激及病理变化,可能通过抑制烟酰胺腺嘌呤二核苷酸磷酸氧化酶4/活性氧/p38丝裂原活化蛋白激酶信号通路发挥作用。Objective To study the effects of dapagliflozin combined with irbesartan on glucose metabolism and podocyte function in diabetic rats, and to explore related mechanisms. Methods The diabetic model of rats was established by intraperitoneal injection of streptozotocin(STZ). Forty rats were randomly divided into model group, dapagliflozin group, Irbesartan group and combined group, with 10 rats in each group;ten normal rats were selected as control group. The dapagliflozin group was intraperitoneally injected with dapagliflozin 2 mg·kg^(-1), the irbesartan group was intraperitoneally injected with irbesartan 30 mg·kg^(-1), and the combined group was intraperitoneally injected with dapagliflozin 2 mg·kg^(-1)and irbesartan 30 mg·kg^(-1). The model group and the control group were intraperitoneallyinjected with an equal volume of 0. 9% NaCl. The rats in five groups were treated once a day, continuous interventionfor 12 weeks. The glucose metabolism indexes were detected by glucose oxidase coupled colorimetry andradioimmunoassay;the content of malondialdehyde(MDA) in renal tissue was detected by thiobarbituric acid method;the nephrin protein expression in renal podocytes was detected by immunocytochemical staining;the nicotinamideadenine dinucleotide phosphate oxidase 4(NOX4) protein expression was detected by western blotting.Results Thefasting blood glucose(FBG) of the control group, model group, dapagliflozin group, irbesartan group, combined groupwere(5. 23 ± 0. 68),(21. 46 ± 3. 23),(11. 49 ± 2. 61),(11. 78 ± 2. 33) and(7. 05 ± 0. 82) mmol·L^(-1);thecontents of MDA in kidney tissues were(41. 69 ± 5. 97),(115. 20 ± 19. 65),(90. 31 ± 10. 56),(89. 67 ± 11. 31)and( 65. 87 ± 7. 49) nmol·mg^(-1);the expression levels of nephrin protein in podocytes were 1. 52 ± 0. 36,0. 41 ± 0. 05, 0. 70 ± 0. 08, 0. 73 ± 0. 09 and 0. 98 ± 0. 15;the expression levels of NOX4 protein in kidney tissueswere 0. 41 ± 0. 06, 0. 90 ± 0. 11, 0. 71 ± 0. 09, 0. 73 ± 0. 08 and 0. 52 ± 0. 06. There were statistically signifi

关 键 词：达格列净 厄贝沙坦 糖尿病 糖代谢 足细胞功能 

分 类 号：R977.15[医药卫生—药品]