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  

Induction of heine oxygenase-1 hyperexpression prior to ischemia protects kidney against ischemiareperfusion injury in rats

作　　者：肖芳[1] 陈刚[1] 李俊华[1] 向莹[1] 陈松[1] 陈实[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院器官移植研究所,武汉430030

出　　处：《中华器官移植杂志》2008年第3期164-167,共4页Chinese Journal of Organ Transplantation

基　　金：湖北省自然科学基金青年杰出人才项目（2007ABB012）

摘　　要：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48h和24h腹腔注射CoPP2．5mg／kg，然后阻断左肾血流47min，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24h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80min，恢复血流后不处死，观察14d，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24h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24h后也见肾组织中HO-1为高表达。术后14d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。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 left renal 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 reperfusiorL Serum creatinine and BUN were determined to evaluate renal functiorL Renal tissue samples were used for histological examination and detection of the HO-1 expressiorL 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±3. 09）mmol/L respectively, CoPP treatment significantly improved renal function after I/R, the mean serum Cr and BUN levels were （48.92±12. 92）μmol/L and （13. 99± 5.00） mmol/L respectively （P〈0. 05 vs. IRI control group）. Renal ischemia-reperfusion induced obvious pathological changes in the IRI control group, particularly massive tubular infarction and cast formation In contrast, rats pre-treated with CoPP demonstrated significant attenuation of infarction, ischemic glomeruli and cast formatiorz However, obvious tubular vacuolization and edema still existed. Both immunohistochemistry and Western-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- day observation period （P〈0. 05 vs. 2 of 6 rats survived in IRI control group）. Conclusion Pretreatment with CoPP effectively reduced rena

关 键 词：血红素氧化酶(脱环) 缺血 再灌注损伤 肾 大鼠 

分 类 号：R699.2[医药卫生—泌尿科学]