钴原卟啉诱导血红素氧合酶-1高表达减轻大鼠肾脏缺血再灌注损伤

目的 探讨钴原卟啉(CoPP)诱导血红素氧合酶-1(HO-1)高表达对大鼠肾脏缺血再灌注损伤(IRI)的影响及其机理.方法 以Wistar大鼠为实验对象,CoPP组分别于左肾血流阻断前48 h和24 h腹腔注射CoPP 2.5 mg/kg,然后阻断左肾血流47 min,恢复左肾血流的同时切取大鼠右肾,采用免疫组织化学染色和免疫印迹法检测其HO-1的表达.在再灌注24 h后,处死大鼠,取其下腔静脉血和左肾,测定血肌酐(Cr)和尿素氮(BUN)浓度,观察肾组织学变化,检测肾组织中HO-1的表达.IRI组除不用CoPP处理外,其余同CoPP组.CoPP组和IRI组另有部分大鼠的血流阻断时间延长至80 min,恢复血流后不处死,观察14 d,记录其存活情况.结果 IRI组血清Cr及BUN分别为(134.37±24.26)μmol/L和(30.10±3.09)mmol/L,明显高于CoPP组的(48.92±12.92)μmol/L和(13.99±5.00)mmol/L(P＜0.05).IRI组肾小管细胞大片坏死,管型形成,与之相比,CoPP组肾小管坏死范围稍小,但肾小管病变范围仍较广泛,肾小管上皮细胞多处于水变性阶段,"缺血样"肾小球减少,管型形成较少.缺血前及再灌注24 h后,CoPP组的肾组织中HO-1均为高表达,主要位于肾间质的毛细血管处,IRI组再灌注24 h后也见肾组织中HO-1为高表达.术后14 d内,IRI组的6只大鼠中有4只死亡,而CoPP组的5只大鼠全部存活,两组大鼠存活率的差异有统计学意义(P＜0.05).结论 缺血前使用CoPP可减轻大鼠肾脏缺血再灌注损伤,该保护作用可能是通过CoPP诱导肾脏高表达HO-1来实现的.

Induction of heme oxygenase-1 hyperexpression prior to ischemia protects kidney against ischemia-reperfusion injury in rats

Objective To investigate the effects of induction of HO-1 hyperexpression with CoPP on renal ischemia-reperfusion injury(IRI)in a rat model and study the relative mechanisms.Methods A dose of 2.5 mg/kg of CoPP was administered intraperitoneally into Wistar rats 48 h and 24 h before 47 min of the feft renaI ischemia.At the time of reperfusion,the contralateral kidney was removed for detection of basic HO-1 expression by using immunohistochemistry and Western-blot.Blood and kidney samples were collected 24 h after reperfusion.Serum creatinine and BUN were determined to evaluate renal function.Renal tissue samples were used for histological examination and detection of the HO-1 expression.Except for CoPP treatment,the same procedure was done in IRI control group.Additionally,prolongation of renal ischemia time to 80 min was undertaken to study the protective effects of CoPP on rat mortality.Results The mean serum creatinine and BUN levels in the IRI control rats were(134.37±24.26)μmol/L and(30.10 Westem-blot revealed that hyperexpression of HO-1 was successfully induced in kidney by CoPP,which mainly located in interstitial capillaries.Furthermore,survival data showed that all rats in CoPP-treated group survived until the end of the 14-dav observation period(P＜0.05 vs. 2 of 6 rats survived in IRI control group).Conclusion Pretreatment with CoPP effectively reduced renal ischemia-reperfusion injury in rats,which might be due to the induced HO-1 hyperexpression in kidneys.