Study of the expression of tissue transglutaminase and connective tissue growth factor in kidneys from UUO rats

Objective To investigate the effect of enalapril on the expression of tTG,CTGF and its mechanism on renal interstitial fibrosis following unilateral ureteral obstruction(UUO) in rat kidney.Methods Unilateral ureteral obstruction(UUO) rat animal models were used.Male wistar rats were randomly divided into three groups with 8 rats in each:sham-operated group(0.9% saline solution),model group(0.9% saline solution),enalapril treatment group(enalapril 10 mg·kg-1·d-1).Sham-operated rats had their ureters exposed and manipulated but not ligated and snipping.Medicines were given intraperitoneally daily two days after the operation.All rats were killed 4 weeks after surgery,and the kidneys were removed.One part of the kidneys was fixed in 10% phosphate-buffered formalin for pathological and immunohistochemical studies after paraffin embedding.Firstly,renal function was examined in each rat by heart puncture.Secondly,the sites and levels of protein expression of tTG,CTGF and ColⅠwere detected by immunohistochemistry staining.Lastly,the degree of tubulointerstitial fibrosis was scored by HE and Masson staining.Results Compared with sham-operated group,the blood uria nitrogen level was significantly increased in model group [(10.6±1.5)mmol/Lvs (7.1±0.5)mmol/L](P0.01),but serum creatinine was normal in each group.Furthermore,the relative area of interstitial fibrosis was also significantly enlarged in the model group (0.319±0.104 vs 0.039±0.007)(P0.01).Meanwhile,compared with sham-operated group,the expression of tTG,CTGF and Col Ⅰ protein was significantly up-regulated in their kidney tissue(0.243±0.036 vs 0.098±0.003;0.314±0.044 vs 0.004±0.001;0.062±0.015 vs 0.012±0.002)(P0.01或0.05).After intervention with enalapril,the upregulation of the above-mentioned parameters were all significantly inhibited,and there was significant difference between model group and treatment group(P0.01或0.05).Conclusion The effect of enalapril on ameliorating renal interstitial fibrosis may be correlated with its inhibition on over-expression of tTG and CTGF in kidney tissue.