肾胺酶预防大鼠缺血再灌注致急性肾损伤的机制研究  

Mechanism of renalase in prevention of acute renal injury induced by ischemia and reperfusion

作　　者：吴永东[1] 汪华林[1] 林蓉宇 蒋强[1] 袁春玲[1] 

机构地区：[1]广州医科大学附属第一医院肾病科,广州510120

出　　处：《新医学》2016年第1期17-21,共5页Journal of New Medicine

基　　金：国家自然科学基金资助项目(30801140)

摘　　要：目的探讨肾胺酶在预防肾脏缺血再灌注(IR)致急性肾损伤(AKI)的作用及机制。方法选择36只SD大鼠制作IR-AKI模型,随机分成假手术组(仅游离出双侧肾蒂,不夹闭肾动脉)、空白对照组(IR组,缺血前30 min腹腔注射生理盐水)、肾胺酶干预组(IR+肾胺酶组,缺血前20 min腹腔注射肾胺酶1 mg/kg)3组。于IR 18 h后,取肾脏组织行苏木素-伊红染色和免疫组织化学检查,光镜下观察病理学改变,比较凋亡相关蛋白Bcl-2和Bax的表达水平;静脉采血测血尿素氮、血清肌酐和丙二醛含量。结果 IR+肾胺酶组的血清肌酐、血尿素氮和丙二醛水平和急性肾小管坏死指数均低于IR组(P均<0.01)、高于假手术组(P均<0.01)。IR+肾胺酶组的Bcl-2蛋白表达均高于IR组和假手术组(P<0.01)。IR+肾胺酶组的Bax蛋白表达低于IR组(P<0.01)、高于假手术组(P<0.01)。结论肾胺酶可减轻肾脏IR导致的AKI,其机制可能是通过抑制氧化应激产物的产生,并与上调Bcl-2抗凋亡蛋白和下调Bax促凋亡蛋白表达有关。Objective To investigate the effect and mechanism of renalase in preventing acute kidney injury （AKI） induced by renal ischemia/reperfusion （IR）. Methods A total of 36 IR-AKI SD rat models were established and randomly divided into the sham-operated group （ renal pedicle was separated without renal artery clipping） , normal control （IR group, intraperitoneal injection of normal saline at 30 min before ischemia） group and renalase intervention group （ IR ＋ renalase group, intraperitoneal injection of 1.5mg/kg of rena- lase at 30 rain before ischemia）. At 18 h after IR, renal tissues were collected for H. E staining and immunohistochemical analysis and observed for pathological changes under light microscope. The expression levels of Bcl-2 and Bax were detected and statistically compared among three groups. The contents of serum creatinine, urea nitrogen and serum malonyldialdehyde were measured. Results The levels of serum creatinine, urea nitrogen, serum malonyldialdehyde and acute tubular necrosis scoring index in the IR ＋ renalase group were significantly lower than those in the IR group （ all P 〈 0.01 ）, whereas considerably higher compared with those in the shame-operated group （all P 〈 0. 01 ）. The expression of Bcl-2 in the IR ＋ renalase group was significantly higher compared with those in both the IR and shame groups （ both P 〈0. 01 ）. The expression level of Bax in the IR ＋ renalase group was significantly lower than that in the IR group （ P 〈 0. 01 ） but dramatically higher compared with that in the sham-operated group （P 〈 0. O1 ）. Conclusions Renalase can alleviate IR-induced AKI probably by inhibiting the production of oxidative stress products, down-regulating the expression of of Bax and up-regulating the expression of Bcl-2.

关 键 词：肾胺酶 缺血再灌注 急性肾损伤 氧化应激 凋亡 

分 类 号：R692.5[医药卫生—泌尿科学]