摘要
为了研究miR-155在内毒素血症幼鼠肝损伤中的作用,将60只幼年Wistar鼠随机分为内毒素模型组、miR-155抑制组和空白组。模型组幼鼠通过腹腔内一次性注射LPS(20mg/kg)构建内毒素血症模型。miR-155抑制组幼鼠在腹腔内注射LPS后,再经尾静脉注射miR-155抑制剂(80mg/kg)。空白组幼鼠腹腔内注射等量生理盐水。各组建模2d后,进行肝脏生化指标、肝组织病理学、肝细胞凋亡、炎症蛋白、通路蛋白等项目的检测。实验结果表明,模型组幼鼠血液内miR-155的表达量、丙氨酸氨基转移酶(alanine aminotransferase,ALT)和天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)水平显著高于空白组,miR-155抑制组ALT和AST水平显著低于模型组(P<0.05);模型组幼鼠肝细胞肥大且不规则,细胞排列紊乱,胞浆空泡增多;空白组幼鼠肝细胞排列整齐,仅少量肝细胞颗粒变性;miR-155抑制组肝细胞病理变化较少,细胞结构较完整;模型组细胞凋亡指数(apoptosis index,AI)、TNF-α和IL-10水平显著高于miR-155抑制组(P<0.05)和空白组(P<0.05);模型组Bcl-2/Bax显著低于空白组(P<0.05)和miR-155抑制组(P<0.05);模型组Ras同源基因A蛋白(Ras homolog gene family member A,RhoA)、Rho相关螺旋卷曲蛋白激酶1(Rho-associated coiled coil-forming protein kinase 1,ROCK1)和Rho相关螺旋卷曲蛋白激酶2(Rho-associated coiled coil-forming protein kinase 2,ROCK2)水平明显升高,而miR-155抑制组3种蛋白水平均显著下降。以上发现提示,miR-155可能通过调控Rho/ROCK通路参与内毒素血症幼鼠的肝损伤。
We aimed to explore the effect of miR-155 in liver injury of rats with LPS-induced endotoxaemia and the underlying mechanism.60 young Wistar rats were randomly divided into the endotoxaemia model group,the miR-155 inhibition group and the blank group.Rats of the endotoxaemia group were injected with 20 mg/kg of LPS intrapenitoneally,and those of the miR-155 inhibition group were given miR-155 inhibitor(80 mg/kg)following LPS injection,while rats of the blank group received same volume of normal saline.Two days later,liver biochemical indexes,liver histopathology,liver tissue apoptosis,inflammatory cytokines and signaling molecules involved in Ras signal transduction pathway were analyzed.The results showed that,blood levels of miR-155,alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in the model group were significantly higher than those in the other two groups(P<0.05),histopathology examination displayed more severe hepatocellular injury in the model group than the miR-155 inhibition group.In addition,levels of apoptosis index(AI),TNF-αand IL-10 in the model group were significantly higher than those in the blank group(P<0.05)and the miR-155 inhibition group(P<0.05).Furthermore,ratio of Bcl-2/Bax in the model group was significantly decreased than the miR-155 inhibition group(P<0.05).Finally,The levels of Ras homolog gene family member A(RhoA),Rho-associated coiled coil-forming protein kinase 1(ROCK1)and Rho-associated coiled coil-forming protein kinase 2(ROCK2)were significantly increased in the model group than in the other two groups.Taken together,these findings indicate that miR-155 participates liver injury during LPS-induced endotoxaemia in young rats.
作者
曾晓靓
闵青
ZENG Xiao-liang;MIN Qing(Department of Newborns,Jiujiang Maternal and Child Health Hospital,Jiujiang,332000,China)
出处
《现代免疫学》
CAS
CSCD
北大核心
2020年第1期41-47,共7页
Current Immunology
基金
江西省卫生厅科技计划立项课题(20141370).
