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| 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 |
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| DOI： |
| 中文关键词: 右美托咪定 JAK/STAT 通路 肝移植 肾损伤 |
| 英文关键词: Dexmedetomidine Liver transplantation JAK/STAT pathway Kidney injury |
| 基金项目: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) |
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| 中文摘要: |
| 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30 min 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(10 mg/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6 h(S 组术毕后6 h),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(p-STAT1)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。 |
| 英文摘要: |
| 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 =10 each)using a random number table:sham operation group (group S);autologous orthotopic liver transplantation model group (group M);dexmedetomidine group (group D);JAK2 kinase inhibitor AG490 group (group A);dexmedetomidine+atipamezole group (group T).In group D,rats received dexmedetomidine 50 μg/kg 30 min before establishing model;In group A,rats re-ceived AG490 10 mg/kg 30 min before establishing model;In group T,rats received atipamezole (250 μg/kg)30 min prior to dexmedetomidine treatment.Other groups were given the equal volume of normal saline in the same time points.At 6 h after 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 determina-tion of the pathologic changes which were scored;Cell apoptosis was assessed by TUNEL,and apop-tosis index(AI)was calculated.The expression of phosphorylations of JAK2,STAT1 and STAT3 were 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,P-STAT1 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 up-regulated in group T (P < 0.05 ). Conclusion Dexmedetomidine can attenuate kidney injury after autologous orthotopic liver transplan-tation,and the mechanism is associated with inhibiting the JAK/STAT pathway activation, alleviating inflammation reaction and cell apoptosis. |
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