复方仙草颗粒对IgA肾病大鼠肾脏保护作用的研究

PROTECTIVE EFFECT OF COMPOUND XIANCAO GRANULE ON KIDNEY IN RATS WITH IgA NEPHROPATHY

目的:观察中药制剂复方仙草颗粒对IgA肾病大鼠的肾脏保护作用,并探讨其可能机制。方法:采用一侧肾脏切除、反复尾静脉注射较大剂量葡萄球菌肠毒素B(SEB)方法制备IgA肾病大鼠模型。大鼠随机分为模型组、福辛普利组、复方仙草颗粒小、中、大剂量组,另设正常对照组。分组给药,疗程8周。检测大鼠血清IgA水平、24小时尿蛋白定量和肾组织TGF-β1mRNA(实时荧光定量PCR法)和蛋白(Western印迹)表达;进行肾小球系膜细胞计数和肾组织纤粘蛋白(FN,免疫化学法)表达检测。结果:(1)复方仙草颗粒各组大鼠血清IgA含量及24小时尿蛋白定量均明显改善(P<0.05,P<0.01);福辛普利组与模型组比较,血清IgA含量无显著改善(P>0.05)。(2)复方仙草颗粒各组及福辛普利组TGF-β1mRNA及蛋白表达较模型组明显降低(P<0.01);(3)复方仙草颗粒各组及福辛普利组肾小球系膜细胞数及FN表达较模型组均显著降低(P<0.05,P<0.01)。结论:复方仙草颗粒能减少IgA肾病大鼠尿蛋白,延缓肾小球硬化,其作用机制可能与抑制TGF-β1表达与信号转导及降低血清IgA水平有关。

Objective: To observe the protective effect of compound Xiancao granules on kidney in rats with IgA nephropathy( IgAN) and to ex- plore the possible action mechanism of compound Xiancao granules. Methods: A rat model of IgAN was established by unilateral nephrectomy and repeated injection of large dose of staphylococcal entero- toxin B via the caudal vein. All the IgAN rats were randomly divided into model group,fosinopril group,low,middle,and high dose compound Xiancao granule groups,healthy mice were chosen as normal control group,the course of treatment was 8 weeks in all groups. Serum IgA level and 24hour urinary protein excretion were determined; the mRNA and protein expression of transforming growth factor- β1( TGF- β1) in renal tissue was measured by real- time quantitative PCR and Western blot; glomerular mesangial cells were counted under a light microscope,and the expression of fibronectin( FN) in renal tissue was measured by immunohisto- chemistry. Results: All compound Xiancao granule groups showed significant decreases in serum IgA level and 24hour urinary protein excretion compared with the model group( P < 0. 05 or P < 0. 01). The fosinopril group had nonsignificantly decreased on serum IgA level compared with the model group( P > 0. 05). Compared with the model group,all compound xiancao granule groups and fosinopril group had significantly decreased in mRNA and protein expression of TGF- β1( P < 0. 01) and significantly decreased mesangial cell count and FN expression( P < 0. 05 or P < 0. 01). Conclusion: Compound xiancao granules can reduce urinary protein excretion and delay glomerular sclerosis in IgAN,possibly by in- hibiting TGF- β1 expression and signaling and decreasing serum IgA level.