结缔组织生长因子在阿霉素肾病中表达的变化及霉酚酸酯干预作用研究

目的分析阿霉素肾病中结缔组织生长因子(CTGF)的变化,研究霉酚酸酯对其干预作用及机制。方法24只SD大鼠随机分为对照组、阿霉素肾病模型组、阿霉素肾病霉酚酸酯治疗组。大鼠尾静脉一次注射阿霉素75mg·kg-1,治疗组第6周开始霉酚酸酯粉末20mgkg-1d-1混悬于1ml蒸馏水中灌胃,10周时处死所有大鼠,观察肾组织病理变化,应用免疫组织化学方法和原位杂交技术检测CTGF在肾组织中的表达。结果阿霉素肾病组大鼠较对照组肾小球系膜及基质明显增生,免疫组织化学染色及原位杂交显示肾小球和肾小管区CTGF蛋白及CTGFmRNA表达量明显上升(P<005),霉酚酸酯治疗组肾小球系膜及基质的增生程度较阿霉素肾病组明显减轻,肾小球和肾小管区CTGF蛋白及CTGFmRNA表达量明显低于阿霉素肾病组(P<005)。结论阿霉素肾病动物CTGF表达增加,观察到间质纤维化表现;霉酚酸酯可以减轻间质纤维化,延缓慢性肾病发展,其机理可能是通过下调CTGF的表达。

Study on the Change of Connective Tissue Growth Factor in Adriamycin Nephropathy and the Effect of Mycophenolate Mofetil

Objective: To investigate the change of connective tissue factor (CTGF) in adriamycin nephropathy rats, and study the effect of mycophenolate mofetil on adrimycin nephropathy rats and its possible mechanism. Methods:Twenty-four SD rats were divided into 3 groups at random: normal control group(n=8), adriamycin nephropathy group(adriamycin i.v. at 7.5 mg kg~-1 from vena caudalis,n=8), and MMF treated group(MMF 20 mgkg~-1 d~-1 by daily gastric gavage from the 6th week,n=8).Observed the pathology of the renal tissue through light microscopy.The expression of connective tissue growth factor(CTGF) were analyzed by immunohistochemistry and in situ hybridization. Results:The proliferation of the mesangial cells and the accumulation of the extracellular matrix in adriamycin nephropathy rats were severe than in control group, the expression of CTGF protein and CTGF mRNA in glomerulars and tubles increased significantly(P<0.05);mycophenolate mofetil treatment ameliorated the proliferation, reduced the expression of CTGF protein and CTGF mRNA obviously(P<0.05). Conclusion: The expression of CTGF increased in adriamycin nephropathy rats with the appearance of renal interstitial fibrosis;mycophenolate mofetil can reduce the expression of CTGF and ameliorate interstitial fibrosis,slow the progression of chronic renal disease. [