益肾通络方对肾病综合征大鼠肾功能的保护作用
【摘要】 目的：观察益肾通络方对实验性肾病综合征大鼠肾功能的保护作用。方法：采用尾静脉注射阳离子化牛血清白蛋白造模。将40只雄性SD大鼠随机分为模型组、益肾通络方组、肾炎四味片组、正常对照组，每组10只。造模后予以药物干预，共给药4 w。采用化学比色法检测24 h尿蛋白，光镜下切取肾组织进行病理形态学观察。结果：与模型组比较，肾炎四味片组和益肾通络方组大鼠24 h尿蛋白量明显降低（P0.01）；而2组之间比较，益肾通络方组大鼠24 h尿蛋白量降低更显著（P0.01）。病理形态学观察：模型组肾小球呈局灶性节段性硬化，肾小管上皮细胞水肿，部分小管腔内可见蛋白管型，肾间质纤维化；肾炎四味片组以上改变较同期模型组轻，而益肾通络方组显著减轻。结论：益肾通络方能降低大鼠尿蛋白，保护肾功能。
Abstract Objective：To observe the protective effects of Yishen Tongluo decoction on renal function of rats with nephrotic syndrome. Methods：40 SD rats were randomly divided into normal group，model group，Shenyan Siwei pill treatment group，Yishen Tongluo decoction treatment group（n=10）. Except for normal group，the rats of other groups were injected cationic bovine serum albumin（C—BSA） through tail veins，then treatment drugs were given to corresponding rats for 4 weeks. 24 h proteinuria of rats were measured by chemical colorimetry，and kidney tissues of rats were observed by light microscopy. Results：Compared with the model group，the contents of 24 h proteinuria of Shenyan Siwei pill treatment group and Yishen Tongluo decoction treatment group were decreased obviously（P＜0.01）. Compared with Shenyan Siwei pill treatment group，the contents of 24 h proteinuria of Yishen Tongluo decoction treatment group were decreased obviously（P＜0.01）. In the pathological sections of model group，focal segmental glomerular sclerosis，dropsy in renal tubular epithelial cells，protein cast in some renal tubules and tubulointerstitial fibrosis could be seen. Compared with the model group，the pathology changes of Shenyan Siwei pill treatment group were decreased，and those of Yishen Tongluo decoction treatment group were decreased significantly. Conclusions：Yishen Tongluo decoction can decrease proteinuria of rats and protect renal function of rats with nephrotic syndrome.
Key words nephrotic syndrome; Yishen Tongluo decoction; proteinuria; rat。
肾病综合征（nephrotic syndrome，NS）是多种病因引起肾小球基底膜通透性增高，使大量血浆蛋白由尿中丢失而导致的一种综合征，临床具有大量蛋白尿、低蛋白血症、高胆固醇血症、不同程度的水肿四大特点。肾病综合征是临床常见病、多发病，且治疗棘手，容易复发，难以巩固。本实验采用经典NS模型阳离子化牛血清白蛋白（C—BSA）造模大鼠，通过24 h尿蛋白定量测定及病理形态学观察，研究益肾通络方降低大鼠尿蛋白、保护肾功能的作用。
1 材料与方法。
1．1 实验材料。
1．1．1 实验动物 40只普通级雄性健康SD大鼠，体重（150±20）g，购自广州中医药大学实验动物中心。合格证号：粤监证字2005A031SCXK（粤）2003—0001。
1．1．2 药品与试剂 益肾通络方汤剂，由湖南中医附一院药剂科制备。肾炎四味片，湖北亿雄祥瑞药业有限公司出品，批号：国药准字Z42021954。C—BSA， 磷酸盐缓冲液（PBS），弗氏不完全佐剂。
1．2 实验方法。
1.2.1 造模 取30只大鼠参照参考文献［1］方法造模。预免疫：将60 mg C—BSA用30 mL PBS充分溶解，制成2 mg/mL C—BSA溶液，再与等量（30 mL）的弗氏不完全佐剂置乳钵内充分混匀为乳白色悬液，使乳化完全。取1 mL乳白色悬液，分别一次性在每只大鼠的双侧腋下、腹股沟处作多点皮下注射，观察1 w。免疫：预免疫结束1 w后，每只大鼠隔日尾静脉注射1 mL浓度为2.5 mg/mL的C—BSA，共3 w。整个造模时间共4 w。
1.2.2 分组与给药 将造模后的30只大鼠，按24 h尿蛋白定量结果分为3个区组，然后再随机分为模型组、益肾通络方组、肾炎四味片组，每组10只，将10只同批未造模大鼠作为正常对照组。造模4 w分组后，益肾通络方组灌服益肾通络方汤剂（2.17 g/kg），肾炎四味片组灌服肾炎四味片（2.45 g/kg）混悬液，模型组和正常对照组每天灌服等容量（1 mL/100 g）的冷开水，每天灌胃1次，连续给药治疗4 w。大鼠每周称重1次，根据体重调整给药剂量。