右美托咪定通过抑制JAK/STAT通路减轻自体原位肝移植大鼠的肾损伤  

Dexmedetomidine attenuates kidney injury after autologous orthotopic liver transplantation via inhibiting the JAK/STAT signaling activation

作　　者：王菲[1] 贾莉莉[1] 翁亦齐[2] 张全胜 杜洪印[2] 喻文立[2] 

机构地区：[1]天津医科大学一中心临床学院,300192 [2]天津市第一中心医院麻醉科 [3]天津市器官移植重点实验室

出　　处：《临床麻醉学杂志》2016年第11期1120-1124,共5页Journal of Clinical Anesthesiology

基　　金：天津市卫生行业重点攻关项目(13KG105);天津市卫生局科技基金(2011KY12);天津市应用基础研究计划面上项目(05YFJMJC14800)

摘　　要：目的探讨Janus激酶/信号转导和转录激活子(Janus kinase/signal transducer and activator of transcription,JAK/STAT)通路在右美托咪定减轻大鼠自体原位肝移植肾损伤的作用。方法 SD大鼠50只采用随机数字表法分为五组(n=10):假手术组(S组),仅开关腹并游离相应血管;模型组(M组),制备大鼠自体原位肝移植模型;右美托咪定组(D组),造模前30min腹腔注射右美托咪定50μg/kg;JAK2激酶抑制剂AG490组(A组),造模前30 min腹腔注射AG490(10mg/kg);右美托咪定^+阿替美唑组(T组),在注射右美托咪定30 min前腹腔注射阿替美唑250μg/kg,之后操作同D组。S、M和D组在与A和T组相应时点腹腔注射等量生理盐水。肝循环开放后6h(S组术毕后6h),经肝下下腔静脉采集血样后处死大鼠,取肾组织。检测血清肌酐(Cr)、尿素氮(BUN)、IL-6和TNF-α浓度;观察肾组织病理学改变,行肾小管病理损伤评分;TUNEL法检测肾脏细胞凋亡情况并计算凋亡指数(AI);Western blot法检测磷酸化JAK2(p-JAK2)、STAT1(pSTAT1)和STAT3(p-STAT3)蛋白的表达水平。结果与S组比较,M、D、A和T组大鼠IL-6、TNF-α、Cr、BUN浓度,肾小管损伤评分及AI明显升高,p-JAK2、p-STAT1和p-STAT3蛋白表达水平明显升高(P<0.05);与M组比较,D与A组IL-6、TNF-α、Cr、BUN浓度、肾小管损伤评分及AI明显降低,p-JAK2、p-STAT1和p-STAT3蛋白表达水平明显降低(P<0.05);与D组比较,T组IL-6、TNF-α、Cr、BUN浓度、AI及肾小管损伤评分明显升高,且p-JAK2、p-STAT1和p-STAT3蛋白表达水平明显升高(P<0.05)。结论右美托咪定减轻大鼠自体原位肝移植肾损伤的机制可能与抑制JAK/STAT通路激活从而减轻炎性反应和细胞凋亡有关。Objective To investigate the role of Janus kinase and signal transducer and activator of transcription（JAK/STAT）signaling pathway in dexmedetomidine＇s renoprotection after autologous orthotopic liver transplantation in rats.Methods Fifty SD rats were randomly divided into five groups（n=10each）using a random number table：sham operation group（group S）;autologous orthotopic liver transplantation model group（group M）;dexmedetomidine group（group D）;JAK2kinase inhibitor AG490group（group A）;dexmedetomidine~＋atipamezole group（group T）.In group D,rats received dexmedetomidine 50μg/kg 30 min before establishing model;In group A,rats received AG490 10mg/kg 30 min before establishing model;In group T,rats received atipamezole（250μg/kg）30 min prior to dexmedetomidine treatment.Other groups were given the equal volume of normal saline in the same time points.At 6hafter reperfusion,rats were sacrificed,blood samples were harvested for detecting the serum concentration of creatinine（Cr）,blood urea nitrogen（BUN）,interleukin-6（IL-6）and tumor necrosis factor-alpha（TNF-α）.kidneys were removed for determination of the pathologic changes which were scored;Cell apoptosis was assessed by TUNEL,and apoptosis index（AI）was calculated.The expression of phosphorylations of JAK2,STAT1 and STAT3were assessed by Western blot.Results Compared with group S,the levels of Cr,BUN,IL-6,TNF-α,AI and renal tubular damage score were significantly increased,and the expression of p-JAK2,PSTAT1 and P-STAT3 was up-regulated in other groups（P〈0.05）;Compared with group M,the levels of Cr,BUN,IL-6,TNF-α,AI and renal tubular damage score were significantly decreased,and the expression of p-JAK2,P-STAT1 and P-STAT3 was down-regulated in groups D and A（P〈0.05）;Compared with group D,atipamezole have abolished dexmedetomidine＇s renoprotection,the levels of Cr,BUN,IL-6,TNF-α,AI and renal tubular damage score were significantly increased,and the expression of p-JAK2,P-STAT1 and P-STAT3 was

关 键 词：右美托咪定 JAK/STAT通路 肝移植 肾损伤 

分 类 号：R614[医药卫生—麻醉学]