中介素后处理对肾脏缺血再灌注损伤后微血管密度及缺氧诱导因子的影响  

Effects of intermedin postconditioning on microvessel density and expression of hypoxia inducible factor in renal ischemia-reperfusion injury

作　　者：苏雯[1] 李荣山[2] 王晨[1] 

机构地区：[1]山西医科大学第二医院肾内科 山西省肾脏病研究所,太原030001 [2]山西省人民医院肾内科 山西省肾脏病研究所

出　　处：《中国药物与临床》2013年第11期1394-1396,I0001,共4页Chinese Remedies & Clinics

基　　金：国家自然科学基金(30971380)

摘　　要：目的探讨中介素(IMD)后处理对大鼠肾脏缺血再灌注损伤(IRI)后损伤肾组织微血管密度(MVD)及缺氧诱导因子(HIF-1α)表达的影响。方法正常雄性SD大鼠24只随机分为:假手术组(Sham组)、IRI组、IRI+IMD组和IRI+0.9%氯化钠注射液(NS)组。大鼠右肾切除1周后左肾制作肾脏IRI模型。各组分别于恢复血流后的24 h留取血液及肾组织标本。检测血清的尿素氮和肌酐水平;过碘酸雪夫(PAS)染色观察肾组织的病理变化;CD31免疫组织化学标记MVD计数;实时荧光定量-聚合酶链反应(RT-PCR)法检测HIF-1αmRNA的表达。结果 IRI、IRI+NS、IRI+IMD组的尿素氮、肌酐水平和肾小管及间质病理损伤均明显高于Sham组(均P<0.01);IRI+IMD组的尿素氮、肌酐水平以及肾小管和间质病理损伤也较IRI和IRI+NS组显著减低或减轻(均P<0.01)。与Sham组相比,IRI及IRI+NS组肾间质的MVD增多;IRI+IMD组肾间质的MVD较IRI及IRI+NS组增多更为明显(均P<0.01)。RT-PCR结果显示:IRI及IRI+NS组HIF-1αmRNA表达较Sham组增多;IRI+IMD组HIF-1αmRNA表达较IRI及IRI+NS组显著增多(均P<0.01)。结论中介素作为后处理药物能够在肾脏IRI后增加缺血组织的MVD并上调血管生成因子HIF-1α的表达,从而参与损伤肾组织的血管新生。Objective To investigate the effects of intermedin （IMD） postconditioning on microvessel density （MVD） and expression of hypoxia inducible factor （HIF-1α） in rats with renal ischemia-reperfusion injury （IRI）.Methods A total of 24 Sprague-Dawley rats were randomly allocated to Sham control,IRI,IRI＋normal saline （NS）and IRI＋IMD group,respectively.Following right renal resection,the IRI model was constructed on the left kidney after 1 week.The sera and renal tissue were sampled at 24 hour following reperfusion in all groups.This entailed determination of the levels of blood urea nitrogen （BUN） and serum creatinine （Scr） and PAS staining for analysis on the pathologic changes of the kidney.Immunohistochemistry assay targeting CD31 was employed to quantify the MVD count,and fluorescent quantitative reverse transcriptase polymerase chain reaction （RT-PCR） was conducted to assay the HIF-1α mRNA expression.Results Compared with Sham control group,the levels of BUN and Scr and tubulointerstitial injury were significant higher in IRI,IRI＋NS and IRI＋IMD group （all P＜0.01）,particularly in the latter group （all P＜0.01）.Compared with Sham control group,a higher level of MVD in renal interstitium was noted in IRI,IRI＋NS and IRI＋IMD group,particularly in the latter group （all P＜0.01）.Quantitative RT-PCR assay suggested a similar pattern of change in the HIF-1α mRNA expression （all P＜0.01）.Conclusion Intermedin postconditioning promotes angiogenesis in renal injury via induction of an increase in MVD and up-regulation of HIF-1α expression in rats following renal ischemia-reperfusion injury.

关 键 词：肾脏 缺血 再灌注损伤 中介素 缺氧诱导因子-1Α 血管新生 

分 类 号：R363[医药卫生—病理学]