罗格列酮对急性胰腺炎大鼠肺组织HMGB1和JAK2/STAT3信号通路调控的研究

Research on the regulation of rosiglitazone on signaling pathways of HMGB1 and JAK2/STAT3 in pulmonary tissue of rats with acute pancreatitis

目的探讨罗格列酮对SAP模型大鼠早期炎症介质、晚期炎症因子HMGB1和JAK2/STAT3信号通路表达的调控。方法72只SD大鼠随机分为3组,假手术组(SO组,n=24)、胰腺炎模型组(SAP组,n=24)和罗格列酮组(ROSI组,n=24)。SAP组在麻醉后两次腹腔内注射左旋精氨酸,ROSI组在SAP建模后30 min静脉注射罗格列酮针6 mg/kg,SO组在麻醉后腹腔注射等体积生理盐水。3组术后6、12和24 h分别采样(每个时间点n=8),测定血清TNF-α、IL-1β、IL-6等早期炎症因子含量,观察大鼠肺组织病理改变,测定肺髓过氧化物酶和肺干/湿重比,检测肺组织HMGB1、JAK2、STAT3蛋白表达情况。结果ROSI组大鼠的血清IL-1β、IL-6、TNF-α含量较SAP组明显降低,差异有统计学意义(P<0.05);与SAP组比较,ROSI组的肺组织病理损伤减轻,肺MPO表达降低,干/湿重比下降,HMGB1、JAK2、STAT3蛋白表达明显减低,差异有统计学意义(P<0.05)。结论罗格列酮能抑制肺组织JAK2、STAT3表达,降低早期、晚期炎症因子表达,减轻SAP导致的肺损伤。

Objective To investigate the expression regulation of rosiglitazone on signaling pathways of HMGB1 and JAK2/STAT3 in early inflammatory mediators,late inflammatory factors of rats with SAP model.Methods A total of 72 SD rats were randomly divided into the sham operation group(SO,n=24),the pancreatitis model group(SAP,n=24)and the rosiglitazone group(ROSI,n=24).The SAP group was injected with L-arginine intraperitoneally twice after anesthesia,the ROSI group was injected with rosiglitazone by 6mg/kg intravenously 30 minutes after SAP modeling,and the SO group was injected with the same volume of normal saline intraperitoneally after anesthesia.Samples were taken at 6 hours,12 hours and 24 hours after operation in three groups(n=8,at each time point).The contents of early inflammatory factors such as TNF-α,IL-1β,IL-6 in serum were detected.The pathological changes of rat pulmonary tissue were observed,the pulmonary myeloperoxidase and the pulmonary dry/wet weight ratio were detected,and the expression of HMGB1,JAK2 and STAT3 protein in pulmonary tissue were detected.Results The levels of serum IL-1β,IL-6 and TNF-α in the ROSI group were remarkably lower than those in the SAP group,with statistically significant differences(P<0.05).Compared with the SAP group,in the ROSI group,the pathological injury of pulmonary tissue was alleviated,MPO expression in lung was decreased,dry/wet weight ratio was lowered,and HMGB1,JAK2,STAT3 protein expression were remarkably reduced,with statistically significant differences(P<0.05).Conclusion Rosiglitazone can inhibit the expression of JAK2 and STAT3 in pulmonary tissue,reduce the expression of early and late inflammatory factors,and alleviate pulmonary injury caused by SAP.