右归丸对激素抵抗型肾病综合征大鼠模型及SD蛋白的影响

Effect of Yougui Pill on Rat Model and SD Protein of Steroid-Resistant Nephrotic Syndrome

目的观察右归丸对激素抵抗型肾病综合征(steroid-resistant nephrotic syndrome,SRNS)大鼠24 h尿蛋白定量、肾脏功能及足细胞裂孔隔膜(SD)相关蛋白的影响。方法 60只健康雄性Wistar大鼠随机分为正常组(10只)和造模组(50只)。造模组大鼠采用一次性尾静脉注射阿霉素(6 mg/kg),正常组大鼠尾静脉一次性注射等剂量的生理盐水,造模成功2周后,采用随机数字表法分为模型组、激素组、激素联合中药高、中、低组。正常组、模型组等体积生理盐水、激素组泼尼松片混悬液、激素联合中药组右归丸与泼尼松混悬液,连续灌胃干预6周。治疗期间观察大鼠的一般情况,检测各组大鼠24 h尿蛋白定量;给药结束后,应用生化分析仪检测大鼠血生化指标,采集肾组织,采用免疫组织化学检测大鼠肾小球中Nephrin、Podocin变化和分布情况。结果与空白组比较,其它各组尿蛋白、总胆固醇、三酰甘油、肌酐与尿素氮明显增加升高(P <0. 05);血白蛋白含量降低明显(P <0. 05);与模型组相比,各治疗组尿蛋白、血脂、肾功指数下降明显(P <0. 05);血白蛋白含量升高(P <0. 05)。与正常组相比,其它各组Nephrin、Podocin表达量有所减少(P <0. 05);与模型组相比,各治疗组除激素组外其它各组Nephrin、Podocin表达量均有上调(P <0. 05);与正常组比较,Nephrin、Podocin沿肾小球毛细血管袢呈片状、不连续型颗粒布散;与模型组比较,各治疗组Nephrin、Podocin蛋白分布无统计学意义(P> 0. 05)。结论右归丸对激素有增敏作用,可明显减少24 h尿蛋白量,降血脂、提高血清蛋白,保护肾功能,有效恢复足细胞SD相关蛋白的表达量,进而延缓SRNS的进展。

Objective To observe the effects of Yougui pill on the 24 h urinary protein,renal function and slit diaphragm(SD)molecules expression in rat with steroid-resistant nephrotic syndrome(SRNS).Methods Sixty health male Wistar rats were randomly divided into control group(n=10)and modeling group(n=50).Rats of modeling group were injected by doxorubicin(6 mg/kg)via the tail vein,and the normal group was injected by the same amount of saline.Two weeks after the modeling,rats of modeling were sub-divided into model group,hormone group,and high-dose,middle-dose,low-dose traditional Chinese drug combined with hormone group.The rats in the normal group and model group were given gastric gavage of same volume of normal saline,rats in hormone group were given gastric gavage of prednisone aqueous solution,and rats in high-dose,middle-dose,low-dose was given by gastric gavage of Yougui pill and prednisone suspension.During 6 weeks treatment process,the general situation of the rats was observed,and the 24 h urine protein of each group was measured.After the completion of medication,serum biochemical levels were measured by biochemical analyzer,and the renal samples were collected.The changes and distribution of nephrin and podocin in rats’glomeruli were detected by immunohistochemistry.Results Compared with the normal group,urinary protein,TC,TG,Scr and BUN increased significantly(P<0.05),and the content of serum albumin decreased significantly(P<0.05).Compared with the model group,the urine protein,blood lipids and renal function indices of each treatment group decreased significantly(P<0.05).The content of serum albumin increased(P<0.05).The results of immunohistochemistry showed that the expression of nephrin and podocin in other groups were lower than that in the normal group(P<0.05).Compared with the model group,except the hormone group,the expression of nephrin and podocin in each treatment group were higher than that in the model group(P<0.05).Compared with the normal group,nephrin and podocin showed a liner distribution along the glomerular capillary loop,and nephrin and podocin in other groups was in the form of sheet-like and discontinuous granules.Compared with the model group,the distribution of nephrin and podocin protein in each treatment group was not statistically significant(P>0.05).Conclusion Yougui pill has sensitization effect on hormone.Yougui pill could reduce 24 h urinary protein quantity of SRNS rats and improve renal function protect the kidney from damage by reducing the blood lipid content,increased the serum albumin level,and restored the reduced slit diaphragm(SD)molecules expression,thus delaying the progression of SRNS.