当归红芪超滤膜提取物调控p38 MAPK/CREB信号通路对糖尿病肾病大鼠的肾脏保护作用研究

Effects of Angelica sinensis and Astragalus membranaceus ultrafiltration membrane extract regulating p38 MAPK/CREB signaling pathway on renal protection in diabetic nephropathy rats

关键词:  糖尿病肾病  当归红芪超滤膜提取物  丝裂原活化蛋白激酶p38/cAMP反应元件结合蛋白  肾脏保护  氧化应激  炎症反应

Key words:  diabetic nephropathy  Angelica sinensis and Astragalus membranaceus ultrafiltration membrane extract  mitogen-activated protein kinase p38/cAMP response element-binding protein  renal protection  oxidative stress  inflammatory response

摘要:

[目的]探究当归红芪超滤膜提取物调控p38丝裂原活化蛋白激酶（p38 MAPK）/cAMP反应元件结合蛋白（CREB）信号通路对糖尿病肾病（DKD）大鼠的肾脏保护作用。[方法]选取SPF级40只雄性SD大鼠，10只大鼠作为对照组，30只构建DKD模型，共有27只大鼠建模成功，分为模型组9只、当归红芪超滤膜提取物组9只、激活剂组9只。观察各组大鼠病理组织学、肾功能、炎症因子、氧化应激指标、p38 MAPK/CREB通路mRNA与蛋白表达量。[结果]与对照组相比，模型组胱抑素C（CysC）、血肌酐（Scr）、尿素氮（BUN）、丙二醇（MDA）、细胞间黏附分子-1（ICAM-1）、白细胞介素（IL）-6、IL-8、肿瘤坏死因子-α（TNF-α）升高，谷胱甘肽过氧化物酶（GSH-Px）、超氧化物歧化酶（SOD）降低（P<0.05）；与模型组相比，当归红芪超滤膜提取物组CysC、Scr、BUN、MDA、ICAM-1、IL-6、IL-8、TNF-ɑ降低，GSH-Px、SOD升高（P<0.05）；与归红芪超滤膜提取物组相比，激活剂组CysC、Scr、BUN、MDA、ICAM-1、IL-6、IL-8、TNF-ɑ升高，GSH-Px、SOD降低（P<0.05）。与对照组相比，模型组p38 MAPK、CREB mRNA与蛋白表达量升高（P<0.05）；与模型组相比，当归红芪超滤膜提取物组p38 MAPK、CREB mRNA与蛋白表达量降低（P<0.05）；与当归红芪超滤膜提取物组相比，激活剂组p38 MAPK、CREB mRNA与蛋白表达量升高（P<0.05）。[结论]当归红芪超滤膜提取物可减轻DKD大鼠炎症反应，抑制氧化应激反应，具有肾脏保护作用，其作用机制可能与调控p38 MAPK/CREB信号通路有关。

Abstract:

[Objective] To explore the renal protective effect of Angelica sinensis and Astragalus membranaceus ultrafiltration membrane extract regulating p38 mitogen activated protein kinase（p38 MAPK）/cAMP response element binding protein（CREB） signal pathway on diabetes nephropathy（DKD）rats. [Methods] Forty male SD rats with SPF grade，10 rats as control group，30 rats were selected to construct DKD model，a total of 27 rats were successfully modeled，and were divided into model group 9，angelica red Astragalus ultrafiltration membrane extract group 9，and activator group 9. Histopathology，renal function，inflammatory factors， oxidative stress index，mRNA and protein expression of p38 MAPK / CREB pathway were observed. [Results] Compared with the control group，the model group showed in cystatin C（CysC），serum creatinine（Scr），blood urea nitrogen（BUN），propylene glycol （MDA），intercellular adhesion molecule-1（ICAM-1），interleukin（IL）-6，IL-8，tumor necrosis factor-α（TNF-α），glutathione peroxidase （GSH-Px）increased，and glutathione peroxidase（GSH-Px），superoxide dismutase（SOD）decreased（P<0.05）；compared with model group，the levels of CysC，Scr，BUN，MDA，ICAM-1，IL-6，IL-8 and TNF-α in Angelica Astragalus ultra-filtration membrane extract group were decreased，while the levels of GSH-Px and SOD were increased（P<0.05）. The levels of CysC，Scr，BUN，MDA，ICAM-1，IL-6， IL-8 and TNF-ɑ in the activator group were increased，while the levels of GSH-Px and SOD were decreased（P<0.05）. Compared with control group，mRNA and protein expressions of p38 MAPK and CREB in model group were increased（P<0.05）. Compared with model group，the mRNA and protein expressions of p38 MAPK and CREB in Angelica Radix Astragalus ultrafiltration membrane extract group were decreased（P<0.05）. Compared with Angelica sinensis and Astragalus membranaceus ultrafiltration membrane extract，the mRNA and protein expressions of p38 MAPK and CREB in activator group were increased（P<0.05）. [Conclusion] Angelica sinensis and Astragalus membranaceus ultrafiltration membrane extract can reduce inflammation，inhibit oxidative stress and protect kidney in DKD rats，and its mechanism may be related to the regulation of p38 MAPK/CREB signaling pathway.