抑制IGF-2表达对脓毒症大鼠肺损伤的保护作用  

Protective Effect of Inhibition of IGF-2 Expression on Lung Injury in Septic Rats

作　　者：西任古丽·孜能 郑军[1] 刘丽丽[1] 刘斌 王娅丽 XI REN GULI·Zineng;ZHENG Jun;LIU Li-li;LIU Bin;WANG Ya-li(Department of Critical Care Medicine,The No.6 Affiliated Hospital of Xinjiang Medical University,Urumqi 830000,China)

机构地区：[1]新疆医科大学第六附属医院重症医学科,新疆乌鲁木齐830000

出　　处：《药物生物技术》2021年第6期585-589,共5页Pharmaceutical Biotechnology

摘　　要：探讨抑制IGF-2对脓毒症肺损伤大鼠的保护作用。将40只大鼠随机分为假手术组、模型组、siRNAIGF-2组、siRNA-NC组,通过盲肠穿刺法建立脓毒症模型,假手术组麻醉后开腹不进行盲肠结扎,siRNA-IGF-2组和siRNA-NC组大鼠在造模前24 h鼻腔滴入siRNA-IGF-2及siRNA-NC。通过RT-qPCR检测各组大鼠肺组织IGF-2 mRNA表达水平,ELISA检测各组大鼠血清白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β),HE染色法观察各组大鼠肺组织病理变化,TUNEL法检测各组大鼠肺组织细胞凋亡情况,Western-blot检测IGF-2、PI3K、AKT、p-PI3K、p-AKT蛋白表达水平。与假手术组比,模型组、siRNA-NC组和siRNA-IGF-2组大鼠肺组织IGF-2 mRNA和蛋白表达水平显著升高(P<0.05),肺泡结构受损,肺泡壁增厚,出现大量炎性浸润,大鼠血清IL-6、TNF-α、IL-1β含量显著升高(P<0.05),肺组织细胞凋亡率显著升高(P<0.05),p-PI3K、p-AKT蛋白表达水平显著升高(P<0.05);与siRNA-NC组比,siRNA-IGF-2组大鼠肺组织IGF-2 mRNA和蛋白表达水平显著下降(P<0.05),炎性细胞浸润得到显著改善,大鼠血清IL-6、TNF-α、IL-1β含量显著下降(P<0.05),肺组织细胞凋亡率显著下降(P<0.05),p-PI3K、p-AKT蛋白表达水平显著下降(P<0.05)。抑制IGF-2表达能够降低脓毒症肺损伤大鼠炎性浸润,抑制肺组织细胞凋亡,其机制可能与IGF-2调节PI3K/AKT信号通路有关。To investigate the protective effect of inhibition of IGF-2 on sepsis lung injury in rats,40 rats were randomly divided into sham group,model group,siRNA-IGF-2 group and siRNA-NC group.The sepsis model was established by cecal puncture.The rats in the sham group were anesthetized without cecal ligation,and the rats in the siRNA-IGF-2 group and siRNA-NC group were dropped siRNA-IGF-2 or siRNA-NC into the nasal cavity 24 h before the modeling.Expression levels of IGF-2 mRNA in lung tissues of rats in each group were detected by RT-qPCR,serum IL-6,TNF-αand IL-1βwere detected by ELISA,pathological changes of lung tissues of rats in each group were observed by HE staining,apoptosis of lung tissues of rats in each group was detected by TUNEL assay,and protein expression levels of IGF-2,PI3K,AKT,p-PI3K and p-AKT were detected by Western-blot.Compared with the sham group,the model group,siRNA-NC group and siRNA-IGF-2 set of rat lung tissue IGF-2 mRNA and protein expression were significantly increased(P<0.05),the alveolar structure was damaged,thickening of alveolar walls,appearing a large number of inflammatory infiltrates,rat serum IL-6,TNF-αand IL-1βcontent significantly increased(P<0.05),lung tissue apoptosis rate increased significantly(P<0.05),p-PI3K,p-AKT protein expression level was significantly increased(P<0.05).Compared with the siRNA-NC group,siRNA-IGF-2 set of rat lung tissue IGF-2 mRNA and protein expression level decreased significantly(P<0.05),inflammatory cells infiltration were improved significantly,the rat serum IL-6,TNF-αand IL-1βcontent decreased significantly(P<0.05),and lung tissue apoptosis rate dropped significantly(P<0.05),p-PI3K,p-AKT protein expression level decreased significantly(P<0.05).Inhibition of IGF-2 expression could reduce inflammatory infiltration and inhibit lung apoptosis in septic rats with lung injury,and the mechanism might be related to the regulation of PI3K/AKT signaling pathway by IGF-2.

关 键 词：胰岛素样生长因子-2 脓毒症 肺损伤 白介素-6 肿瘤坏死因子-α 白介素-1Β PI3K/AKT信号通路 

分 类 号：R966[医药卫生—药理学]