Effects Of Erythropoietin On Renal Tubulointerstitial Fibrosis And Bcl-2/Bax Expression After Renal Ischemia/reperfusion-induced Kidney Injury In Mice

AbstractObjective:To investigate effects of erythropoietin on renal tubulointerstitial fibrosis and Bcl-2 (anti-apoptotic protein)/Bax(pro-apoptotic protein) expression after renal ischemia/reperfusion injury(IRI) in mice. Methods:80 male C57BL/6 mice with 8-12 weeks age were randomly divided into 4 groups:sham-operated control group(n=20), IRI group(n=20), treatment group with low-dose EPO (model rats treated with EPO 100u/kg, Once a week, n=20), treatment group with high-dose EPO(model rats treated with EPO 1000u/kg, once a week, n=20). Left renal artery of mice was clamped for 35min with micro-artery clamp to make model of renal IRI. The morphological changes were observed by HE and Masson stain. Meanwhile, the expression of Bcl-2 and Bax in renal tissue were assessed by immunohistochemical method. Results:â‘ Pathological changes, which demonstrated tubular atrophy, expansion, interstitial fibrosis, inflammatory cell infiltration, and increased scores of tubulointerstitial fibrosis with varying degrees, were found in IRI group, but these pathological changes in treatment groups with low-and high-dose EPO were significantly improved as compared with the IRI group(P<0.05 or 0.01). Bcl-2 and Bax were mainly stained in renal tubular and interstitium with the standard immunohistochemistry. Compared with the sham-operated group, the levels of Bcl-2 and Bax expression were remarkably increased (P<0.01), the ratio of Bcl-2/Bax was remarkably decreased in IRI group (P<0.01). Compared with the IRI group, Bax expression was significantly reduced, Bcl-2 expression and the ratio of Bcl-2/Bax were incresead in treatment groups with low-and high-dose EPO(P<0.01). Increased espression of Bcl-2 in treatment group with high-dose EPO was higher than that in treatment group with low-dose EPO(P<0.01).â‘¢The degree of renal tubulointerstitial fibrosis was correlated with Bcl-2, Bax and Bcl-2/Bax ratio (r=-0.790, P<0.01; r=0.571, P<0.01; r=-0.802, P<0.01). Conclusions:1. Abnormal expression of Bcl-2/Bax is involved in development of renal tubulointerstitial fibrosis after ischemia/reperfusion-induced kidney injury.2. EPO can attenuate the renal tubulointerstitial fibrosis of renal IRI, and might has some relationship with EPO dose; 3. Effects of EPO on renal tubulointerstitial fibrosis after renal ischemia/reperfusion-induced kidney injury may be associated with the regulation of Bcl-2/Bax axis.