摘要
目的:研究氯沙坦在肾缺血/再灌注损伤中对STAT-1和ICAM-1蛋白表达的影响及在损伤修复过程中的作用。方法:大鼠背部双侧切开找到肾蒂,行无创动脉夹夹闭造成急性肾缺血/再灌注损伤模型,以氯沙坦预处理灌胃,苦味酸法测血清肌酐,免疫组化测肾组织切片中的STAT-1蛋白和ICAM-1蛋白表达的水平。结果:假手术组在6h和24h肾组织的病理和血肌酐数值无明显变化;模型组在缺血再灌注6h和24h与假手术组对比血清肌酐数值明显升高,肾组织切片在6h时STAT-1和ICAM-1蛋白已有表达,24h时两指标表达均明显上调;氯沙坦预处理组在缺血再灌注损伤6h和24h时与模型组对比,血肌酐数值明显下降,同时肾组织中STAT-1和ICAM-1蛋白表达也明显下调。结论:氯沙坦在肾缺血再灌注损伤中起保护作用,机制可能通过下调STAT-1和ICAM-1蛋白表达有关。
Objective：To investigate the possible effect of Losartan on the expressions of STAT - 1 and ICAM - 1 in rats with renal ischemic -reperfusion injury（ IRI）, in order to explore its effects in rats with renal IRI. Methods：Thirty -six healthy male wistar rats were randomly divided into three groups ： sham groups, model groups, Losartan treatment group （ n = 12）. Within each group, rats were randomly divided into two subgroups ： IR6h and 1R24 h groups （ each subgroup n = 6）. The renal models of acute is- chemia - reperfusion were made in rats by placing the vascular clamp in bilateral renal pedicle to block the blood circulation for 45 mi- nutes. In sham group, renal arteries were founded but not clipped for 45 minutes. The Losartan treatment group were treated by injec- ting into stomach with Losartan potassium （80 mg · kg ^- 1 · d ^- 1 ） for 7 days before ischemla respectively. The sham and model groups were received the same volume of the distilled water for 7 days before surgery. The level of blood serum creatinine（Scr） was measured 6 h and 24 h after reperfusion, then the rats were euthanized in batch. Histopathological damages were monitored accordingly. The ex- pressions of STAT - 1 and ICAM - 1 in renal tissue were measured by immunohisto - chemical stain. Results： In sham group, the re- nal pathological are normal and the level of Scr did not change clearly. In model group, the level of Scr was markedly higher than that of the sham group 6 h and 24 h after reperfusion respectively（both P 〈 0.05） Further, the protein expressions of STAT - 1 and ICAM - 1 in renal tissue were detected 6 h after reperfusion, and to peak 24 h later. Compared with model group, the level of Scr was lower 6 h and 24 h after reperfusion in Losartan group. As well, the expression of STAT - 1 and ICAM - 1 were markedly lower than model group at the same time point after reperfusion （P 〈 0.01 ）. Conclusion：The pretreatment of Losartan can protect renal function against the renal ischemia- reperfusion injury. As the levels of blood serum creatinine decreased, the expression level of STAT - 1 and ICAM - 1 protein were markedly downregulated after the ischemia - reperfusion injury. These results imply that Losartan whose mech- anism may be involved in the inhibition of STAT - 1 expression can protect renal against the acute renal ischemia/reperfusion injury.
出处
《中国中西医结合肾病杂志》
2012年第8期669-671,I0002,共4页
Chinese Journal of Integrated Traditional and Western Nephrology
