摘要
目的观察淫羊藿苷对局灶节段性肾小球硬化(FSGS)模型大鼠泼尼松抵抗的影响,探讨其可能的作用机制。方法48只Wistar雄性大鼠随机分为对照组(10只)和造模组(38只),大鼠尾静脉注射阿霉素(6.0mg/kg)制备FSGS模型,大鼠尿蛋白>100mg/24h并随机选取2只造模大鼠的肾组织病理为FSGS提示造模成功,其余36只大鼠随机分为模型组(10只)、泼尼松组(10只)、淫羊藿苷组(8只)、泼尼松联合淫羊藿苷组(联合组,8只),给予相应药物灌胃干预6周,称重,检测24h尿蛋白(24h-UTP)、尿素氮(BUN)、肌酐(SCr)、总蛋白(TP)、白蛋白(ALB)、胆固醇(CHOL)、三酰甘油(TG)、皮质醇(COR)、尿17-羟皮质醇(U17-OHCS)水平,HE和Masson染色观察肾组织病理变化,Westernblot和RT-PCR分别检测Nephrin、Podocin蛋白和mRNA表达。结果与对照组比较,模型组大鼠体质量降低,出现大量蛋白尿,肾功能损害严重,伴低蛋白血症及高脂血症,血COR、U17-OHCS含量明显降低(P<0.01),病理显示肾小球出现硬化灶并缩小,部分肾小管内可见蛋白管型,Nephrin、Podocin蛋白和mRNA表达明显降低(P<0.01);与模型组比较,泼尼松组和淫羊藿苷组大鼠上述异常无明显改善,联合组低体质量、蛋白尿、肾功能及代谢异常明显改善,病理损伤改善,血COR、U17-OHCS含量明显升高(P<0.05,P<0.01),Nephrin、Podocin蛋白和mRNA相对表达量明显升高(P<0.05)。结论淫羊藿苷可改善FSGS模型大鼠对泼尼松的抵抗性,其机制可能与保护足细胞相关。
Objective To observe the effects of icariin on prednisone resistance in rat models with focal segmental glomerulosclerosis(FSGS);To explore its possible mechanism of action.Methods Totally 48 Wistar male rats were randomly divided into control group(10)and modeling group(38).FSGS models were prepared by injection of doxorubicin(6.0 mg/kg)into the tail vein of rats.Rat urine protein>100 mg/24 h and 2 randomly selected rats were taken for renal histopathology as FSGS for successful modeling.The remaining 36 rats were randomly divided into model group(10),prednisone group(10),icariin group(8),and prednisone combined with icariin group(joint group,8).Relevant medicine was given for gavage for 6 weeks.The rats were weighted,and 24 h urinary protein(24 h-UTP),urea nitrogen(BUN),creatinine(SCr),total protein(TP),albumin(ALB),cholesterol(CHOL),triglyceride(TG),cortisol(COR),and 17-hydroxycortisol(U17-OHCS)were detected.The pathological changes of renal tissues were observed by HE staining and Masson staining.The expressions of Nephrin,Podocin protein and mRNA were detected by Western blot and RT-PCR,respectively.Results Compared with the control group,body mass of model group decreased;a large amount of proteinuria,severe renal function impairment,hypoproteinemia and hyperlipidemia occurred;COR and U17-OHCS decreased(P<0.01);pathologically,glomerular sclerosis appeared and narrowed;protein tubular type was observed in some renal tubules;the expressions of Nephrin,Podocin protein and mRNA significantly decreased(P<0.01).Compared with the model group,prednisone group and icariin group had no significant improvement on the above abnormalities.The joint group significantly improved low body weight,proteinuria,renal function and metabolic abnormalities;pathological damage was alleviated;the contents of COR and U17-OHCS significantly increased(P<0.05,P<0.01);the relative expression levels of Nephrin and Podocin protein and mRNA significantly increased(P<0.05).Conclusion Icariin can improve the resistance of prednisone in FSGS rats,and its mechanism may be related to the protection of podocytes.
作者
陈威辛
戴恩来
王新斌
薛国忠
CHEN Weixin;DAI Enlai;WANG Xinbin;XUE Guozhong(College of Integrated Chinese and Western Medicine,Gansu University of Chinese Medicine,Lanzhou 730000,China;Affiliated Hospital of Gansu University of Chinese Medicine,Lanzhou 730020,China)
出处
《中国中医药信息杂志》
CAS
CSCD
2019年第11期46-51,共6页
Chinese Journal of Information on Traditional Chinese Medicine
基金
国家自然科学基金(81760799)
甘肃省高校科研专项(2305136302)
