摘要
目的 研究霉酚酸酯 (骁悉 )对实验性狼疮性肾炎肾小球硬化的防治作用。方法 用NZB/BINJ和NZW /LacJ近交系小鼠杂交制备BWF1自发性狼疮小鼠模型。予该模型鼠 10 0mg·kg-1·d-1霉酚酸酯灌胃2 0周。采用考马斯亮蓝法测定 2 4h尿蛋白量 ,采用ELISA法测定血清抗dsDNA抗体水平 ,采用免疫组织化学法检测肾组织中Ⅰ、Ⅳ型胶原的表达 ,采用逆转录 巢式PCR法检测小鼠肾组织中TGF β1mRNA的表达。结果 蛋白尿发生前给予霉酚酸酯可完全抑制小鼠蛋白尿的产生 ,显著降低其血清抗dsDNA抗体水平 ,明显减少小鼠肾组织中TGF β1mRNA和Ⅰ、Ⅳ型胶原的表达并改善其组织学病变。结论 霉酚酸酯对该狼疮模型的肾小球硬化具有明确保护作用。其降低肾Ⅰ、Ⅳ型胶原沉积可能是通过抑制小鼠肾组织局部TGF
Objective To study the protective effect of mycophenolate mofetil on experimental lupus nephritic glomerulosclerosis. Methods 100 mg·kg -1·d -1 mycophenolate mofetil was administrated orally to BW F1 mice. 24-hour urine protein excretion was measured by Coomassie's Brilliant Blue method. The serum level of anti-dsDNA antibodies was assayed by ELISA. The expressions of collagen type Ⅰ and Ⅳ of the mice kidney were estimated by immunohistochemistry. The expression of tissue TGF-β 1 mRNA was analyzed by RT-nested-PCR.Results Mycophenolate mofetil suppressed the development of proteinuria completely before the occurrence of proteinuria, it significantly decreased the level of serum anti-dsDNA antibodies, and the expressions of TGF-β 1 mRNA, collagen type Ⅰ and Ⅳ, also ameliorated the renal histological injury and raised the mice survival rate.Conclusion Mycophenolate mofetil has definite protective effects on glomerulosclerosis of the lupus model. The decrease of renal collagen type Ⅰ and Ⅳ is probably due to its suppressive effect on the expression of TGF-β 1 of kidney tissue.
出处
《上海医学》
CAS
CSCD
北大核心
2002年第7期420-423,T001,共5页
Shanghai Medical Journal