诱导型一氧化氮合酶和血红素氧合酶-1在百草枯中毒大鼠肾脏中的表达

摘要

Objective To study the mechanism of paraquart-induced renal injury in rats,the expression of heine oxygenase-2(HO-1) and inducible nitric oxide synthase (iNOS).Methods 84 adult healthy Spragne-Dawley (SD) rats (female and male in half) were randomly divided into two groups,the control group (group A,n=42) and the paraquart group (group B,n=42).The rats in group B were treated with paraquart (25 mg/kg) intraperitoneally,the rats in group A were treated with the same dose of normal saline.Its histopathological change,the expression of HO-1,iNOS and evaluate the mRNA expression of HO-1 were observed.Results ①In group A,the tissue structure was clear without abnormal.In group B,there were obvious lesions in the renal tubule of cortical part,including cellular swelling,the canula narrow,the mesenchymal congestion and edema.These pathologic changes gradually reached the peak on the 1st day,and did not relieved till the end ofthis study.②In group A,there was no or weak expression of iNOS.At the 3rd hour,the expressions of iNOS in group B were observed in the kytoplasm of renal tubular epithelial cell and glomemlar endothelial cell of cortical part.It reached the peak on the 1st day and continued at a high level after that.③ In group A,there was no or weak expression of HO-1 and HO-1 mRNA.At the 3rd hour,the expressions of HO-1 in group B were observed in the membrane and kytoplasm of renal tubular epithehal cell of cortical part,immunohistochemistry score(IHS) was higher,the expression of HO-1 mRNA increased,there was a statistical significance between group B and group A(P<0.05).It reached the peak on the 1st day,and then decreased,there were 110 statistical difference between group B and group A on the 5th day(P>0.05).Conclusions HO-1 and iNOS ale involved in the procedures of renal injury,but its mode of action and regulating path still need further study.%目的 观察百草枯中毒大鼠肾组织中诱导型一氧化氮合酶(iNOS)和血红素氧合酶-1(HO-1)的表达,探讨其可能的病理生理机制.方法 SD大鼠84只随机分为空白对照组(A组)42只和染毒组(B组)42只.B组百草枯(25 mg/kg)、A组等量盐水腹腔注射.观察2组肾组织病理学变化及iNOS、HO-1表达,并检测HO-1 mRNA.结果 ①A组组织结构清晰.未见充血、水肿及空泡变性等病理变化;B组组织结构清晰度下降,染毒3 h即可见充血、水肿及空泡变性等病理变化,1 d达顶峰,其后缓解趋势不明显.②iNOS:A组多不表达;B组染毒后3 h在皮质部肾小管上皮细胞及肾小球内皮细胞的胞质中出现表达,随时间延长明显增强,1 d达高峰,其后维持较强表达.③HO-1与HO-1 mRNA:A组多不表达;B组染毒3 h在皮质部肾d、管上皮细胞的胞膜及胞质HO-1呈阳性表达,免疫组织化学评分(IHS)升高,HO-1 mRNA的表达增强,与A组相比差异有统计学意义(P<0.05),1 d达顶峰,之后减弱,5 d仍有阳性表达,但与A组相比,IHS差异无统计学意义(P>0.05).结论 iNOS和HO-1参与百草枯中毒肾损伤的发病过程,但其作用方式、调节途径等尚需进一步研究.