※：青海大学中青年科研基金项目(项目编号：2011-QYY-6)

曹学锋(1977～)，男，汉族，甘肃籍，副教授

血红素氧合酶-1在低氧条件下对大鼠肾缺血-再灌注损伤的保护机制※

曹学锋，刘杰，王生兰，刘辉琦，文建军

(青海大学医学院，青海 西宁 810001)

摘要目的探讨血红素氧合酶-1(Heme oxygenase-1，HO-1)在低氧预适应时对大鼠肾缺血-再灌注损伤的保护机制。方法建立大鼠的肾缺血-再灌注损伤动物模型，观察大鼠再灌注后肾脏免疫组织化学变化；检测HO-1基因在大鼠肾脏的表达情况。并就上述结果行相关分析。结果与正常对照组相比，CoPP组HO-1mRNA表达量最高，其余依次降低为实验对照组、低氧+ZnPP组、低氧组，差异有显著性(P<0.01)。CoPP组SOD活性最高，其余依次为低氧组、ZnPP组，差异有显著性(P<0.05)。CoPP组MDA含量最低，其余依次升高为低氧组、低氧+ZnPP组、ZnPP组，差异有显著性(P<0.05)。结论经钴原卟啉(CoPP)处理和低氧预适应使HO-1表达增强，肾脏缺血-再灌注时的细胞损伤减轻，其机制可能与降低氧自由基损伤相关。

关键词血红素氧合酶-1肾缺血-再灌注损伤低氧预适应氧自由基

中图分类号R363

文献标识码A

DOI：10.13452/j.cnki.jqmc.2015.03.004

AbstractObjectiveTo investigate the protective effects of heme oxygenase-1(HO-1)in Renal ischemia/reperfusion injury on rats under hypoxia and explore the possible mechanism.Methods Rat renal ischemia/reperfusion injury model was established.The expression of HO-1 mRNA was detected by RT-PCR.The vitality of SOD and the quantity of MDA were detected in rat renal ischemia/reperfusion injury models treated with HO-1 inducer cobalt protoporphyrin(CoPP)，zinc protoporphyrin(ZnPP，HO-1 inhibitor)and hypoxic preconditioning.Results HO-1 mRNA level expression results showed that：compared with normal control group，the CoPP group expression was the highest，the other groups such as control group，hypoxia+ZnPP group，hypoxia group，also showed significant difference(P<0.01).SOD activity in CoPP group was the highest，followed with low oxygen and ZnPP group，respectively，showed significant difference(P<0.05).MDA content in CoPP group was the lowest，while the hypoxia，hypoxia+ZnPP group and ZnPP group showed significant difference(P<0.05) as well.Conclusion The up regulation of HO-1 expression induced by CoPP and hypoxic preconditioning can reduce the degree of damage of the tubular epithelial cells and subsequently alleviate the renal ischemia reperfusion injury.One of its main mechanisms may be related with anti oxygen free radicals.

Keywordsheme oxygenase-1renal ischemic /reperfusion injuryhypoxic preconditioningoxygen free radical

收稿日期2015-04-02

THE PROTECTIVE EFFECT OF HEME OXYGENASE-1 IN

RENAL ISCHEMIA/REPERFUSION INJURY ON

RATS UNDER HYPOXIA

Cao Xuefeng，Liu Jie，Wang Shenglan，Liu Huiqi，Wen Jianjun

(Qinghai University Medical College，Xining QingHai，810001)

近年来肾缺血-再灌注损伤(renal ischemia repergusion injury，RIRI)保护机制成为器官移植研究热点。血红素氧合酶-1(HO-1)是降解血红素的限速酶和关键酶，HO-1的保护效应是通过其降解产物实现的[1-2]。本实验采用HO-1抑制剂和诱导剂处理实验动物，观察HO-1在肾脏缺血-再灌注损伤模型中的表达，进而探讨HO-1 在肾脏缺血-再灌注损伤中的作用和机制。

1对象与方法

1.1　实验对象和分组

健康SD雄性大鼠60只随机分为6组，每组10只，体重(200±30)g，由甘肃省中医院动物实验中心提供。分组：(1)正常对照组：术前24 h 腹腔注射生理盐水；(2)实验对照组：术前切除右肾，夹闭左肾动脉缺血1 h，而后再灌注3 h；(3)CoPP组，于实验前24 h腹腔注射CoPP(5mg/ kg)，余同(2)组处理；(4)ZnPP组，于实验前24 h 腹腔注射ZnPP(5mg/kg)，余同(2)组处理；(5)低氧组，实验前24 h，放入低压氧仓(海拔4000m)，余同(2)组处理；……