自噬对大鼠原位肝移植术后急性肾损伤的影响  

Effects of autophagy on acute kidney injury after liver transplantation

作　　者：吴莉[1] 施东婧 李国东[2] 杨超[1] 杜洪印[3] 

机构地区：[1]天津医科大学一中心临床学院,300070 [2]天津医科大学第二医院药剂科 [3]天津市第一中心医院麻醉科

出　　处：《中华器官移植杂志》2015年第10期606-610,共5页Chinese Journal of Organ Transplantation

基　　金：天津市卫生行业重点攻关项目（13KG105）;天津市应用基础趼究计划面上项目（05YFJMJC14800）

摘　　要：目的评价自噬在大鼠原位肝移植术后急性肾损伤中的作用。方法56只健康雄性SD大鼠，采用随机数字表法分为4组：假手术组、原位肝移植组（OLT组）、西罗莫司预处理组（SRL组）、3-甲基腺嘌呤预处理组（3-MA组），假手术组为8只，其他3组各8对（16只）进行原位肝移植。再灌注后6h检测各组受鼠肾功能，肾组织氧化应激相关蛋白丙二醛和超氧化物歧化酶（SOD）含量，凋亡相关蛋白caspase-3mRNA和cytCmRNA，以及自噬相关蛋白的表达水平；采用HE染色观察各组肾组织病理学改变，采用TUNEL染色观察肾小管上皮细胞的凋亡情况，应用透射电镜观察肾小管上皮细胞的超微结构的改变。结果与假手术组比较，OLT组受鼠肾功能明显降低，。肾小管上皮细胞可见空泡和管型，刷状缘缺失，肾脏氧化应激及细胞凋亡明显增加；与OLT组比较，SRL组大鼠肾损伤减轻，肾功能改善，氧化应激水平降低，细胞凋亡显著减少，而自噬相关蛋白LC31I和beclin-1的表达明显上调，电镜下可见自噬小体形成增加；与SRL组比较，3～MA组肾损伤程度增加，细胞凋亡增多，自噬水平受到明显抑制。结论自噬可通过减轻肾脏氧化应激及抑制细胞凋亡等途径缓解大鼠肝移植术后急性肾损伤。Objective To evaluate the role of autophagy on acute kidney injury after liver transplantation. Method Fifty-six healthy male Sprague-Dawley rats were randomly assigned into 4 groups： sham group, orthotopic liver transplantation （OLT） group, sirolimus pretreated （SRL） group and 3-methyladenine pretreated （3-MA） group. OLT model was established. Then the rats were sacrificed at 6 h after reperfusion. The renal function and the extent of oxidative stress relative proteins malondialdehyde （MDA） and superoxide dismutase （SOD） were observed. The levels of apoptosis relative genes easpase-3 and cyt c and the expression of autophagy relative proteins were detected. The pathological changes were microscopically examined in renal tissues. TUNEL staining was used to observe the apoptosis of tubular epithelial cells. Transmission electron microscopy was applied to observe the ultrastructure changes of tubular epithelial cells. Result As compared with sham group, OLT and 3-MA groups showed a serious renal injury including cellular vacuolization, loss of brush borders, and a significant rise in BUN, Cr and MDA, while a decrease in SOD activity. The levels of caspase-3 mRNA and cyt c mRNA were increased significantly. Whereas compared to OLT and 3-MA groups, renal function and oxidative stress levels in SRL group ameliorated, and histopathologic damage and apoptosis alleviated after OLT. Simultaneously, the levels of caspase-3 mRNA and cyt c mRNA were decreased. The expression of beclin-I and LC3- Ⅱ was effectively up- regulated. Conclusion Autophagy could alleviate acute kidney injury after liver transplantation through inhibiting oxidative stress and apoptosis.

关 键 词：大鼠 肝移植 肾损伤 自噬 

分 类 号：R657.3[医药卫生—外科学] R692[医药卫生—临床医学]