组织型转谷氨酰胺酶与转化生长因子β1在幼鼠肾间质损伤中的表达及意义

Expression and significance of tissue transglutaminase and transforming growth factor β1 in renal interstitial injury in young rats

目的探讨组织型转谷氨酰胺酶(tTG)和转化生长因子β1(TGF-β1)在幼鼠肾间质损伤中的表达及意义。方法清洁级雄性Wistar幼年大鼠60只,采用随机数字表法分为假手术组、模型组和试验组,每组20只。模型组和试验组幼鼠建立单侧输尿管结扎模型,试验组从建模后第2天起灌胃给予苯那普利和氯沙坦各6mg/(kg·d),1次/天。于造模后第3、7、14、28天,分别处死5只大鼠,取肾组织,采用Masson染色检测肾组织常规病理变化,采用RT-PCR法检测tTG和TGF-β1mRNA表达水平。结果造模后第3、7、14、28天,模型组和试验组肾间质纤维组织相对面积明显高于假手术组,差异有统计学意义(P<0.05),且试验组明显低于模型组,差异有统计学意义(P<0.05)。造模后第3、7、14、28天,模型组和试验组tTG和TGF-β1mRNA均明显高于假手术组,差异有统计学意义(P<0.05),且试验组明显低于模型组,差异有统计学意义(P<0.05)。tTG与TGF-β1和肾间质纤维组织相对面积呈正相关关系,TGF-β1与肾间质纤维组织相对面积呈正相关关系。结论 tTG和TGF-β1互相作用参与肾间质纤维化过程,苯那普利可能通过调节tTG和TGF-β1表达水平实现其肾保护作用。tTG和TGF-β1具有成为肾间质纤维化治疗的潜在有效靶点。

Objective To investigate the expression and significance of tissue transglutaminase（tTG）and transforming growth factorβ1（TGF-β1）in renal interstitial injury in young rats.Methods 60 male Wistar rats were randomly divided into sham operation group,model group and experimental group.The model of unilateral ureteral ligation was established in the model group and the experimental group.The experimental group group received benazepril and losartan 6 mg/（kg.d）,1 time/d from the 2 nd day after the modeling.Five rats were sacrificed at 3 d,7 d,14 dand 28 dafter model establishment.Renal tissue was taken and routine pathological changes were observed by Masson staining.The expression of tTG and TGF-β1 mRNA was detected by RT-CPR.Results The relative area of renal interstitial fibrous tissue in the model group and the experimental group was significantly higher than that in the sham operation group at 3 d,7 d,14 dand 28 d,the difference was statistically significant（P〈0.05）,and the experimental group was significantly lower than the model group,the difference was statistically significant（P〈0.05）.The levels of tTG and TGF-β1 mRNA in the model group and the experimental group were significantly higher than those in the sham operation group at 3 d,7 d,14 dand 28 d,the difference was statistically significant（P〈0.05）,and the experimental group was significantly lower than the model group,the difference was statistically significant（P〈0.05）.There was a significant correlation between tTG and TGF-β1 and the relative area of renal interstitial fibrous tissue.The relative area of TGF-β1 and renal interstitial fibrous tissue had a significant correlation.Conclusion TTG and TGF-β1 interact with renal interstitial fibrosis,and benazepril can achieve its protective effect by down-regulating the expression of tTG and TGF-β1.TTG and TGF-β1 have potential potent targets for renal interstitial fibrosis.