石斛碱对糖尿病肾病大鼠PI3K/Akt/mTOR信号通路及足细胞功能障碍的影响  

Effects of dendrobine on PI3K/Akt/mTOR signaling pathway and podocyte dysfunction in rats with diabetic nephropathy

作　　者：樊小宝 丁通[1] 孙燕[1] 吴冰 王晶 杜鹏[1] FAN Xiaobao;DING Tong;SUN Yan(Nephrotic Hemodialysis Center,Shaanxi Provincial People’s Hospital,Shaanxi,Xi’an 710068,China)

机构地区：[1]陕西省人民医院肾病血透中心,西安市710068

出　　处：《河北医药》2021年第11期1631-1634,1639,共5页Hebei Medical Journal

摘　　要：目的研究石斛碱对糖尿病肾病大鼠PI3K/Akt/mTOR信号通路及足细胞功能障碍的影响。方法建立糖尿病肾病大鼠模型,随机分为模型组、石斛碱低剂量组、石斛碱中剂量组、石斛碱高剂量组、二甲双胍组,每组12只,另取12只SD大鼠设为假手术组,分组处理后,检测大鼠生化指标血糖、血脂、尿微量白蛋白(UMA)水平;以苏木精-伊红(HE)染色检测6组大鼠肾组织病理变化;以酶联免疫吸附法(ELISA)检测大鼠尿中足细胞标志蛋白nephrin、PCX含量及血清白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平;以蛋白免疫印迹法检测肾组织PI3K/Akt/mTOR通路相关蛋白表达水平。结果与假手术组比较,模型组大鼠肾组织出现肾小球基底膜局部增厚,足状突起排列紊乱呈带状结构,局部突起融合、变平,贴敷于基底膜等病理损伤,大鼠血糖、血脂、UMA、TNF-α及IL-6水平、尿中nephrin、PCX蛋白含量显著升高(P<0.05),肾组织中p-PI3K/PI3K、p-Akt/Akt、p-mTOR/mTOR显著降低(P<0.05)。与模型组相比,石斛碱低、中、高剂量组及二甲双胍组大鼠血糖、血脂、UMA、TNF-α及IL-6水平、尿中nephrin、PCX蛋白含量降低(P<0.05),肾组织中p-PI3K/PI3K、p-Akt/Akt、p-mTOR/mTOR升高(P<0.05),且石斛碱各组呈剂量依赖性,石斛碱高剂量组与二甲双胍组比较,各指标差异无统计学意义(P>0.05)。结论石斛碱可能通过激活PI3K/Akt/mTOR通路,减轻糖尿病肾病大鼠足细胞功能障碍,改善其临床症状。Objective To investigate the effects of dendrobine on PI3K/Akt/mTOR signaling pathway and podocyte dysfunction in rats with diabetic nephropathy.Methods The rat models with diabetic nephropathy were established,who were randomly divided into model group,low-dose dendrobine group,middle-dose dendrobine group,high-dose dendrobine group and metformin group,with 12 rats in each group,moreover,the other 12 SD rats were used as sham operation group.After treatment,the levels of blood glucose,blood lipid and urinary microalbumin(UMA)were measured.Moreover,hematoxylin eosin(HE)staining was used to detect the renal pathological changes in each group.Enzyme-linked immunosorbent assay(ELISA)was used to detect the contents of nephrin and PCX as well as the levels of IL-6 and TNF-αin urine.In addition,Western Blot was used to detect the the protein expression of PI3K/Akt/mTOR pathway in renal tissue.Results As compared with those in sham operation group,there appeared the pathological damages including local thickening of glomerular basement membrane,disorganized arrangement of foot like protrusion with banded structure,fusion,flattening of local protrusion and sticking to basement membrane in the renal tissue of rats in model group.Moreover,the levels of blood glucose,blood lipid,UMA,TNF-αand IL-6 as well as the contents of nephrin and PCX protein in urine were significantly increased(P<0.05),however,the expression levels of P-PI3K/PI3K,p-Akt/Akt and p-mTOR/mTOR in renal tissue were significantly decreased(P<0.05).As compared with those in model group,the levels of blood glucose,blood lipid,UMA,TNF-αand IL-6 as well as the contents of nephrin and PCX protein in urine were significantly decreased(P<0.05),however,the expression levels of P-PI3K/PI3K,p-Akt/Akt and p-mTOR/mTOR in renal tissue were significantly increased in low-dose dendrobine group,middle-dose dendrobine group,high-dose dendrobine group and metformin group,with a dose dependent manner,however,there were no significant differences between high-dose dendrobine

关 键 词：石斛碱 糖尿病肾病 PI3K/Akt/mTOR信号通路 足细胞功能障碍 

分 类 号：R587.2[医药卫生—内分泌]