摘要：目的研究大鼠肾小管间质纤维化中转化生长因子β1(TGF-β1)的表达特征。方法以腺嘌呤灌胃法建立大鼠肾小管间质纤维化实验模型，应用免疫组织化学(组化)、逆转录-聚合酶链反应(RT-PCR)、原位杂交及Northernblot检测6只正常及30只模型大鼠肾组织TGF-β1蛋白及基因表达。结果6只正常大鼠肾组织TGF-β1主要位于皮髓交界处肾小管上皮细胞，TGF-β1免疫组化平均阳性表达率为(4．2±0．8)％；损伤的肾小管上皮细胞TGF-β1表达增加，给药1～5周，30只模型肾组织TGF-β1免疫组化平均阳性表达率分别为(8．3±0．4)％、(9．6±0．5)％、(11．5±1．0)％、(16．6±0．8)％及(17．8±0．9)％。各实验组TGF-β1平均阳性表达率均与正常对照组的差异有显著性意义(P＜0．01)；实验组的TGF-β1mRNA表达高于正常组，而且随着肾小管损伤和间质纤维化的日益加重，实验第5周TGF-β1mRNA表达量最高。结论TGF-β1在肾小管间质纤维化中主要由受损伤的肾小管上皮细胞产生，通过自分泌及旁分泌途径发挥促纤维化作用。

The expression of transforming growth factor β1 in tubulointerstitial fibrosis

SUN Mingzhu ,XU Man ,ZOU Wanzhong

(Department of Pathology, Beijing Medical University,Beijing 100083,China)

Abstract：Objective To investigate the expressive feature of transforming growth factor β1 (TGF-β1) in rats with tubulointerstitial fibrosis.Methods The tubulointerstitial fibrosis model was established in 30 Wistar rats by gastroperfusion of excessive adenine.The expressions of protein and mRNA of TGF-β1 were examined utilizing immunohistochemistry,in situ hybridization,reverse transcription polymerase chain reaction and Northern blot.Results The positive signals of TGF-β1 were mainly located in the tubular cells on the juxtamedullary regions and the average positive rate of TGF-β1 was (4.2±0.8)% in 6 normal rats.The positive signals of TGF-β1 in injurious tubular cells were significantly higher than normal and the average positive rates of TCF-β1 were (8.3±0.4)%,(9.6±0.5)%,(11.5±1.0)%,(16.6±0.8)% ,(17.8±0.9)% respectively in experimental rats after gastroperfusion for one to five weeks.There was a significantly difference between the normal and fibrosis rats in the expression of TGF-β1 (P＜0.01 ).The quantity of TCF-β1 mRNA in fibrosis rats was higher than that of the normal and the highest in the fifth week.Conclusion TGF-β1 is a promote growth factor in tubulointerstitial fibrosis,and is synthesized and secreted from injurious tubular cells and acts on interstitial cells.

Keywords：Transforming growth factor β1;Rat;Tubulointerstitial fibrosis;Adenine基金项目：国家自然科学基金资助项目(39770293)

作者简介：孙铭柱，研究生，现在解放军第二炮兵总医院病理科；徐曼，进修生，现在重庆医科大学病理系

参考文献：

［1］Guo G,Morrissey J,McCracken R,et al.Role of TNFR1 and TNFR2 receptors in tubulointerstitial fibrosis of obstructive nephropathy.Am J Physiol,1999,277(5 Pt 2): F766-772.

［2］Wolf G,Ziyadeh FN,Stahl RA.Angiotensin Ⅱ stimulates expression of transforming growth factor beta receptor type Ⅱ in cultured mouse proximal tubular cells.J Mol Med,1999,77:556-564.

［3］Derynck R,Jarrett J A,Chen E Y.Human transforming growth factor-beta cDNA sequence and expression in tumor cell lines.Nature (Lond),1985,316:701-705.

［4］Stokes MB,Holler S,Cui Y,et al.Expression of decorin,biglycan,and collagen type 1 in human renal fibrosing disease.Kidney Int,2000,57:487-498.

［5］徐曼，孙铭柱，邹万忠．尿酸性肾病胰岛素样生长因子和成纤维细胞生长因子的表达．中华肾脏病杂志，1999，15：281-283.

［6］孙铭柱，徐曼，邹万忠．肾小管间质纤维化中成纤维细胞的转化生长因子β1及其Ⅰ型受体蛋白及基因表达检测．临床与实验病理学杂志，2000，16，134-136．

收稿日期：2000-01-07