苯那普利和氯沙坦对肾间质纤维化幼鼠组织型转谷氨酰胺酶和转化生长因子-β_1的抑制作用

Inhibitory effects of benazepril and losartan on tissue transglutaminase and transforming growth factor β_1 in young rats with renal interstitial fibrosis

目的探讨苯那普利和氯沙坦对肾间质纤维化幼鼠组织型转谷氨酰胺酶(tTG)和转化生长因子-β_1(TGF-β_1)的抑制作用。方法雄性wistar幼鼠60只随机分为对照组、模型组和干预组,每组20只。对模型组和干预组幼鼠建立单侧输尿管结扎模型,干预组从建模后第2天起灌胃给予苯那普利和氯沙坦各6mg/(kg·d),1次/天,对照组和模型组灌胃给予等量生理盐水。于实验开始后第3、7、14、28天每组取5只鼠制成标本进行HE染色、Masson染色,采用非生物素标记的PV6001二步法,检测3组肾组织tTG、TGF-β_1的表达。结果 Masson染色结果显示对照组肾间质纤维化面积较小,模型组肾间质纤维化面积显著增加,干预组小部分纤维化面积较模型组降低,差异有统计学意义(P<0.01)。对照组TGF-β_1和tTG表达在对照组较少,模型组高表达,干预组较模型组有所减少,3组比较差异有统计学意义(P<0.01),且随着时间增加,模型组和干预组幼鼠TGF-β_1和tTG表达上升,差异有统计学意义。模型组幼鼠tTG水平与Masson染色面积呈正相关关系(r=0.854,P<0.01);tTG水平与TGF-β_1水平呈正相关关系(r=0.813,P<0.01)。结论肾间质纤维化过程中tTG与TGF-β_1呈正相关关系,苯那普利和氯沙坦抗纤维化作用可能与抑制tTG与TGF-β_1有关。

Objective To investigate the inhibitory effects of benazepril and losartan on tissue transglutaminase(tTG)and transforming growth factor-β1(TGF-β1)in young rats with renal interstitial fibrosis.Methods Sixty male wistar rats were randomly divided into control group,model group and intervention group.The model of unilateral ureteral ligation was established in the model group and the intervention group.The intervention group received benazepril and losartan 6 mg/(kg·d),1 time/d from the 2nd day after the modeling.And the model group and control group were given the same amount of saline.At the 3rd,7th,14th and 28th day after the start of the experiment,5 mice were sacrificed by HE staining and Masson staining.The non-biotin-labeled PV6001 two-step method was used to detect the expression of tTG and TGF-expression.Results Masson staining showed that the area of interstitial fibrosis was smaller in the control group,and was significantly increased in the model group,and was lower in the intervention group than that of the model group(P<0.01).The expression of TGF-β1 and tTG was little in the control group,was high in the model group,and the expression in intervention group was lower than that of the model group,the difference was statistically significant(P<0.01).The expression of TGF-β1 and tTG in the young rats were increased with the time(P<0.01).There was a positive correlation between tTG level and Masson staining area(r=0.854,P<0.01).There was a positive correlation between tTG level and TGF-β1 level(r=0.813,P<0.01).Conclusion tTG is positively correlated with TGF-β1,and tTG can induce fibrosis by up-regulating TGF-β1.The benazepril and losartan can play an anti-fibrosis effect by inhibiting TGF-β1 and tTG.