黄芪甲苷联合氯沙坦对糖尿病大鼠肾组织PI3K/Akt/NF-κB通路的影响  

Effect of astragaloside combined with losartan on PI3K/Akt/NF-κB pathway in diabetic rat kidney

作　　者：刘长青[1] 黄书佳[1] 蒋典 LIU Chang-qing;HUANG Shu-jia;JIANG Dian(Department of Pharmacy,Xiangya Hospital,Central South University,Changsha 410008)

机构地区：[1]中南大学湘雅医院药学部

出　　处：《中南药学》2019年第10期1626-1630,共5页Central South Pharmacy

摘　　要：目的探讨黄芪甲苷联合氯沙坦对糖尿病大鼠肾组织PI3K/Akt/NF-κB信号通路的影响。方法采用尾静脉注射链脲佐菌素(50 mg·kg^-1)的方法建立糖尿病模型,并于4周后检测大鼠24 h尿蛋白排泄量,以≥30 mg视为糖尿病肾病(DN)模型建立成功。随机将DN大鼠分为模型组、黄芪甲苷组(60 mg·kg^-1)、氯沙坦组(30 mg·kg^-1)、黄芪甲苷+氯沙坦组(30 mg·kg^-1+15 mg·kg^-1),另取正常大鼠作为对照,每组10只。各给药组给予相应药物治疗8周,检测大鼠空腹血糖值(FBG)、尿蛋白(UmAlb)及血清肌酐(Scr)、尿素氮(BUN)含量,计算肾组织肥大指数,Western blot法和RTPCR法分别检测PI3K/Akt/NF-κB通路相关蛋白和基因的表达。结果与对照组比较,模型组大鼠肾肥大指数、FBG、UmAlb、Scr、BUN水平均明显升高(P <0.01),肾组织PI3K、Akt磷酸化蛋白及基因表达显著下降(P <0.01),NF-κB表达升高(P <0.01);经黄芪甲苷、氯沙坦单独或联合治疗后,大鼠肾肥大指数、UmAlb、Scr、BUN水平均有明显下降(P <0.01或P <0.05),肾组织PI3K、Akt磷酸化蛋白及基因表达上升(P <0.01或P <0.05),NF-κB表达显著下降(P <0.01)。各给药组之间相互比较发现,联合给药组对大鼠肾肥大指数、UmAlb水平以及PI3K/Akt/NF-κB通路的调控作用较单独给药组更为明显(P <0.05),而黄芪甲苷组与氯沙坦组比较无明显差异。结论黄芪甲苷联合氯沙坦能通过调控PI3K/Akt/NF-κB信号通路改善糖尿病大鼠的肾组织损伤状况,延缓DN的发生发展,且疗效要优于单独给药。Objective To determine the effect of astragaloside combined with losartan on PI3 K/Akt/NF-κB signaling pathway in diabetic rat kidney. Methods Diabetic models were established by tail vein injection of streptozotocin(50 mg·kg^-1) and the 24 h urinary protein excretion was measured after 4 weeks. The diabetic nephropathy(DN) model was successfully established with 24 h urinary protein≥ 30 mg. DN rats were randomly divided into a model group, an astragaloside(60 mg·kg^-1) group, a losartan group(30 mg·kg^-1), an astragaloside + losartan group(30 mg·kg^-1+ 15 mg·kg^-1), and a normal control group(10 rats in each group). Each drug-administration group was given corresponding drug treatment for 8 weeks. The fasting blood glucose(FBG), urine protein(UmAlb), serum creatinine(Scr), and urea nitrogen(BUN) were measured, and the renal hypertrophy index was calculated. Western blot and RT-PCR were used to detect the expression of PI3 K/Akt/NF-κB pathway-related proteins and genes, respectively. Results Compared with those of the control group, the renal hypertrophy index, FBG, UmAlb, Scr and BUN levels in the model group were significantly increased(P < 0.01);the expression of PI3 K, Akt phosphorylation protein and gene in the renal tissue was significantly decreased(P < 0.01), while NF-κB increased(P < 0.01). After the treatment with either astragaloside or losartan alone and combination of both the levels of renal hypertrophy index, UmAlb, Scr and BUN were significantly decreased(P < 0.01 or P < 0.05);the renal tissue expressions of PI3 K, Akt phosphorylation protein and gene were increased(P < 0.01 or P < 0.05), while NF-κB was decreased significantly(P < 0.01). The combined effect on the renal hypertrophy index, UmAlb level and PI3 K/Akt/NF-κ B pathway in the combination group was more obvious than that of the single administration(P < 0.05), but with no significant difference between the astragaloside group and the losartan group. Conclusion Astragaloside combined with losartan improves the renal injury of

关 键 词：糖尿病肾病 PI3K/Akt/NF-κB 黄芪甲苷 氯沙坦 联合给药 

分 类 号：R285.5[医药卫生—中药学]