Aim To investigate the effect of ginseng polysaccharides(WGP) on renal fibrosis in mice with diabetic nephropathy(DN) and its possible mecha-nism. Methods Diabetic mice were induced by intra-venous injection with 120 mg·kg-1streptozotocin (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 o-rally 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 ex-pression of α-SMA protein in renal cortex were detec-ted using Masson staining and immunohistochemical staining. The cAMP content in renal cortex was detec-ted by radioimmunoassay. The protein expressions re-lated 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 de-creasing the expressions of α-SMA,LN and FN protein by inhibiting the activation of cAMP/PKA/CREB sig-nal pathway,which led to the alleviation of degree of glomerular sclerosis and interstitial fibrosis in kidney. Conclusion WGP has inhibitory effect on renal fibro-sis in DN mice model,which might be related with the suppression of cAMP/ PKA /CREB signaling pathway.%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(cAMP)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 cAMP/PKA/CREB信号通路的激活有关.
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