目的:观察柴胡皂苷-d对一侧肾切除加单克隆抗体1-22-3注射造成进行性大鼠肾小球硬化的防治作用.方法:18只大鼠一侧肾切除1 d后,尾静脉注射单克隆抗体1-22-3造成大鼠进行性肾小球硬化.随机分为3组,每组6只.第一组给生理盐水作对照,另外两组分别腹腔注射柴胡皂苷-d 1.8 mg和0.6 mg/kg体重/d.在代谢笼内取大鼠造模后第1、4、8、14和21 d尿液,并动态观察造模后第1、5、10、14和18 d收缩压变化.21 d后处死全部大鼠,进行血生化和肾组织光学显微镜检查,并利用RT-PCR和免疫荧光的方法分析了药物对炎症硬化因子TGF-β、I型胶原、α-平滑肌肌动蛋白(α-SMA)和炎症细胞在肾小球和肾小管间质表达与分布的影响.结果:柴胡皂苷-d在减轻肾小球病理损害的同时,抑制了TGF-β在肾小球内的表达和a-SMA沿鲍曼氏囊的分布.柴胡皂苷-d治疗组CD8+T细胞和巨噬细胞在肾小球周围和肾小管间质的浸润也明显减轻.结论:柴胡皂苷-d能够有效地防治大鼠肾小球硬化,可能与抑制了TGF-β在肾小球内的表达和炎症细胞在肾小球和肾小管间质浸润有关.
Objective: The preventive effects of Saikosaponin-d (Ssd) on the progression of mesangioproliferation and glomerulosclorosis, induced by intravenous injection of anti-Thyl monoclonal antibody (mAb) 1-22-3 into uninephrectomized rats, were evaluated. Methods: Eighteen rats were divided into three groups of six. One group was treated with phosphate buffered saline (PBS) as a control. The other two groups were treated with Ssd 1.8 mg/kg body weight (BW)./day or 0.6mg/kg BW/day respectively. Urine samples were collected from the rats in metabolic cages on days 1, 4, 8, 14 and 21 after the injection of mAb 1-22-3. Systolic BP (SBP) was tested on days 1, 5, 10, 14 and 18 after the injection. All rats were sacrificed 21 days after the injection of mAb 1-22-3 for blood biochemistry, and immunofluorescent and light microscopy of the kidneys. Results: Ssd suppressed proteinuria, extracellular matrix expansion, crescentic formation as well as inflammatorv cell infiltration. Especially, Ssd was shown to have highly significant suppressive effect on CD8T cells infiltration into the periglomerular and tubulointerstitial areas and on expression of TGF-a type Ⅰ collagen in the kidneys and α-SMA along Bowman's capsule. Conclusions: Our study indicates that Ssd could prevent initiation and progression of mesangioproliferative glomerulonephritis in rats through inhibition of CD8+T cell infiltration, macrophage accumulation and activation, and expression of TGF- and type Ⅰ collagen in the kidneys.