重组人MG53对造影剂急性肾损伤的保护作用  

Protective effect of recombinant human mitsugumin 53 on contrast-induced acute kidney injury in rats

作　　者：胡云辉[1] 韩愈[1] 高照[1] 王永斌[1] 仇东峰 张小群[1] 曾春雨[1] 

机构地区：[1]第三军医大学大坪医院野战外科研究所心血管内科,重庆市心血管病研究所,重庆400042

出　　处：《中华高血压杂志》2016年第3期231-236,共6页Chinese Journal of Hypertension

基　　金：国家重点基础研究发展计划(973计划,2013CB531104);国家自然科学基金(81400256)

摘　　要：背景造影剂急性肾损伤已经成为医源性急性肾功能不全的第3大原因,目前尚缺乏特效药物防治造影剂急性肾损伤的发生发展。MG53是新发现的一种肌肉特异性蛋白,属于Tripartite motif（TRIM）家族,具有细胞膜修复功能,推测MG53对造影剂急性肾损伤有保护作用。目的观察重组人MG53（rhMG53）对造影剂急性肾损伤的保护作用及机制。方法将10~12周龄SD大鼠[雌雄各半,体质量（225±15）g]32只采用完全随机分组方法分为对照组、单独rhMG53组（rhMG53组）、造影剂模型组（CM组）、造影剂＋rhMG53组（CM＋rhMG53）4组,每组8只。通过颈外静脉给予吲哚美辛（indomethacin）、一氧化氮合酶抑制剂左旋硝基精氨酸甲酯（l-NAME）及碘普罗胺（iopromide）建立造影剂肾损伤模型。CM＋rhMG53组在造模15min前给予rhMG53（5mg/kg）干预,注射完造影剂24h后测定血清尿素氮、血清肌酐、尿微量白蛋白及肌酐清除率;HE染色观察肾脏病理改变及对肾脏损伤半定量评分;Western blot方法检测各组大鼠肾脏组织cleaved caspase-3、Totol caspase-3、蛋白激酶B（Akt）、磷酸化Akt（p-Akt）、糖原合成酶激酶-3β（GSK-3β）及磷酸化GSK-3β（p-GSK-3β）的表达情况;TUNEL法检测肾脏细胞凋亡情况。结果 CM＋rhMG53组与CM组相比较能够显著改善大鼠肾功能[血肌酐：CM＋rhMG53组（40.98±9.02）比CM组（100.70±14.38）μmol/L;尿素氮：CM＋rhMG53组（18.68±7.87）比CM组（27.18±5.23）mmol/L;肌酐清除率：CM＋rhMG53组（0.99±0.37）比CM组（0.52±0.27）mL/min;尿微量白蛋白：CM＋rhMG53组（18.06±5.32）比CM组（41.67±9.88）mg/24h;均P〈0.05],减轻肾脏病理损伤,增加p-Akt和p-GSK-3β蛋白的表达,减少cleaved caspase-3的表达和肾脏细胞凋亡。结论 rhMG53可对造影剂急性肾损伤产生保护作用。Background Contrast-induced acute kidney injury（CI-AKI）has become the third leading cause of iatrogenic acute renal insufficiency,and still lack of effective treatment to prevent its development.MG53 is a newly identified TRIM-containing family protein primarily expressed in cardiac and skeletal muscles,with the function of cell membrane repair. We hypothesized that MG53 may prevent CI-AKI. Objective The aim of the present study was to assess the effect of rhMG53（recombinant human MG53）on prevention of CI-AKI in rat. Methods SD rats（n=32）in both sexes[10-12 weeks old,weighting（225±15）g]were randomly divided into four groups（n=8each）：control group,rhMG53 group,contrast medium（CM）group and CM＋rhMG53group. The rats were given indomethacin,Nw-nitro-L-arginine methyl ester（l-NAME）and iopromide to establish CI-AKI model. The rats of CM＋rhMG53group were given rhMG53 15 min before the injury. 24 hafter contrast medium was injected,kidney function parameters,including blood urea nitrogen（BUN）,serum creatinine（Scr）,creatinine clearance rate（CCr）and 24 h microalbumin urine（24hMAU）,of all animal test subjects were measured. The pathological changes of the kidney were observed and given semi quantitative score under HE staining. The renal tubular apoptosis was detected by TUNEL and the expressions of cleaved caspase-3,totol caspase-3,Akt,p-Akt,GSK-3βand p-GSK-3βwere detected by Western blot.Results Compared with CM group,CM＋rhMG53group had a significant improvement of renal function[Scr：CM＋rhMG53group（40.98±9.02）vs CM group（100.70±14.38）μmol/L;BUN：CM＋rhMG53group（18.68±7.87）vs CM group（27.18±5.23）mmol/L;CCr：CM＋rhMG53group（0.99±0.37）vs CM group（0.52±0.27）mL/min;24hMAU：CM＋rhMG53group（18.06±5.32）vs CM group（41.67±9.88）mg/24h;all P〈0.05],reduced renal pathological damage,enhanced expression of p-Akt,p-GSK-3β,lowered expression of cleaved caspase-3and less renal tubular apoptosis.Conclusion The study demonstrated that

关 键 词：肾损伤 造影剂 凋亡 重组人MG53 大鼠 

分 类 号：R692[医药卫生—泌尿科学]