Zhong Qing, Leung Joseph C K, Chan Loretta Y Y, Tsang Anita W L, Chen Xian, Lai Kar Neng
Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong.
Am J Chin Med. 2005;33(4):613-26. doi: 10.1142/S0192415X05003211.
IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, yet there is no effective or specific therapy. Shen San Fang (S3F) is a traditional Chinese herbal medicinal formula that has been used in China for many years to treat patients with hematuria. The aim of this study is to test the therapeutic value of S3F in an experimental model of IgAN. IgAN was induced in Lewis rats by continuous oral immunization with bovine gamma-globulin (BGG) in the drinking water for 8 weeks, followed by intravenous injection of 1 mg BGG daily for 3 successive days. The rats were randomly divided into four groups (five rats/group): control, control receiving S3F, induction of IgAN, and IgAN receiving S3E S3F decoction was fed to rats beginning week 4 from the first day of oral sensitization with BGG. The S3F treatment was continued until the rats were sacrificed or for a 4-week period. Hematuria, renal immunohistochemistry for IgA and transforming growth factor-beta 1 (TGF-beta1), renal histopathology, and renal content of TGF-beta1 were measured. Rats developing IgAN had marked hematuria, profound mesangial proliferation and mesangial expansion, intense and diffuse glomerular IgA deposition, increased glomerular TGF-beta1 expression, and raised renal TGF-beta1 levels. S3F treatment resulted in a significant reduction of hematuria, decreased mesangial IgA deposition, weaker immunostaining of TGF-beta1 in glomerulus, and a lower renal TGF-beta1 concentration. Our animal data suggests a therapeutic value for the Chinese medicinal formula S3F in experimental IgAN. This beneficial effect was due to reduced glomerular IgA deposition and TGF-beta1 expression. Our preliminary findings hold promise for future human therapy.
IgA肾病（IgAN）是全球最常见的原发性肾小球肾炎，但尚无有效的特异性治疗方法。肾三汤（S3F）是一种传统的中草药配方，在中国已用于治疗血尿患者多年。本研究的目的是在IgAN实验模型中测试S3F的治疗价值。通过在饮用水中连续口服牛γ球蛋白（BGG）8周诱导Lewis大鼠发生IgAN，随后连续3天每天静脉注射1mg BGG。将大鼠随机分为四组（每组五只大鼠）：对照组、接受S3F的对照组、诱导IgAN组和接受S3F的IgAN组。从用BGG进行口服致敏的第一天起，第4周开始给大鼠喂食S3F汤剂。S3F治疗持续至大鼠处死或为期4周。检测血尿、肾脏IgA和转化生长因子-β1（TGF-β1）的免疫组化、肾脏组织病理学以及肾脏TGF-β1含量。发生IgAN的大鼠有明显血尿、严重的系膜增生和系膜扩张、强烈且弥漫性的肾小球IgA沉积、肾小球TGF-β1表达增加以及肾脏TGF-β1水平升高。S3F治疗导致血尿显著减少、系膜IgA沉积减少、肾小球中TGF-β1免疫染色减弱以及肾脏TGF-β1浓度降低。我们的动物实验数据表明中药配方S3F在实验性IgAN中具有治疗价值。这种有益作用归因于肾小球IgA沉积和TGF-β1表达的减少。我们的初步研究结果为未来的人类治疗带来了希望。
