人参多糖通过cAMP/PKA/CREB信号通路抗糖尿病肾病肾纤维化作用机制研究  

Role of ginseng polysaccharides in renal fibrosis via cAMP/PKA/CREB signaling pathway in diabetic nephropathy

作　　者：黄倩 张素萍 施子禄[3] HUANG Qian;ZHANG Su-ping;SHI Zi-lu(Dept of Physiology,Quanzhou Medical College,Quanzhou Fujian 362100,China;Dept of Physiology,School of Basic Medicine,Zhejiang University,Hangzhou 310058,China;Dept of Nephrology,the First Hospital of Quanzhou Affiliated to Fujian Medical University,Quanzhou Fujian 362000,China)

机构地区：[1]泉州医学高等专科学校基础医学部生理学教研室,福建泉州362100 [2]浙江大学基础医学院生理系,浙江杭州310058 [3]福建医科大学附属泉州第一医院肾内科,福建泉州362000

出　　处：《中国药理学通报》2018年第5期695-701,共7页Chinese Pharmacological Bulletin

摘　　要：目的探讨人参多糖对链脲佐菌素(STZ)诱导的糖尿病肾病(DN)模型小鼠肾纤维化的治疗作用,并揭示其可能的作用机制。方法 STZ(120 mg·kg^(-1))尾静脉注射构建糖尿病小鼠模型,并随机分为模型组、人参多糖(25、50、100 mg·kg^(-1))组、空白组,连续灌胃给药12周。12周末,比较各组小鼠空腹血糖(FBG)、24 h尿微量白蛋白(mAlb)、血清肌酐(Scr)和尿素氮(BUN)含量变化;肾脏Masson染色观察肾脏病理学变化;免疫组织化学法检测肾皮质中α-平滑肌肌动蛋白(α-SMA)表达;放射免疫分析法检测肾皮质中环磷酸腺苷(c AMP)含量;Western blot检测肾皮质中细胞外基质及信号通路PKA/CREB相关蛋白的表达。结果人参多糖能够明显降低DN小鼠FBG、mAlb、Scr、BUN含量,并通过抑制cAMP/PKA/CREB信号通路的激活,降低肾小管上皮细胞表型转化蛋白α-SMA及细胞外基质相关蛋白LN、FN的表达,延缓肾纤维化的进程。结论人参多糖对DN小鼠肾纤维化具有明显的抑制作用,其机制可能与其抑制c AMP/PKA/CREB信号通路的激活有关。Aim To investigate the effect of ginseng polysaccharides(WGP)on renal fibrosis in mice with diabetic nephropathy(DN)and its possible mechanism.Methods Diabetic mice were induced by intravenous injection with 120 mg·kg-1 streptozotocin(STZ)and were randomly divided into the following four groups with 10 mice per group:model group,low-,medium-,high-dose(25,50,100 mg·kg-1)of WGP groups.Other 10 normal mice were treated as normal control group.The mice were administered orally for 12 weeks.After that,the levels of fasting blood-glucose(FBG),microalbuminuria(mAlb),serum creatinine(Scr)and blood urea nitrogen(BUN)were detected.The expression of collagen fibers and the expression ofα-SMA protein in renal cortex were detected using Masson staining and immunohistochemical staining.The cAMP content in renal cortex was detected by radioimmunoassay.The protein expressions related to extracellular matrix composition and PKA/CREB in renal cortex were detected by Western blot.Results WGP could obviously reduce the contents of FBG,mAlb,Scr and BUN in DN mice,meanwhile decreasing the expressions ofα-SMA,LN and FN protein by inhibiting the activation of cAMP/PKA/CREB signal pathway,which led to the alleviation of degree of glomerular sclerosis and interstitial fibrosis in kidney.Conclusion WGP has inhibitory effect on renal fibrosis in DN mice model,which might be related with the suppression of cAMP/PKA/CREB signaling pathway.

关 键 词：糖尿病肾病 人参多糖 环磷酸腺苷 Α-平滑肌肌动蛋白 蛋白激酶A 环磷腺苷效应元件结合蛋白 

分 类 号：R-332[医药卫生] R284.1