罗氟司特对脓毒症炎症大鼠炎症因子及淋巴细胞的调控机制分析

Regulatory Mechanism of Roflumilast on Inflammatory Factors and Lymphocytes in Septic Inflammatory Rats

目的:探究罗氟司特通过JAK/STAT途径对脓毒症炎症大鼠炎症因子及淋巴细胞的调控机制分析。方法:将54只SD大鼠随机分为正常组(n=18),模型组(n=18)和罗氟司特组(n=18),正常组正常喂养,模型组和罗氟司特组建立脓毒症大鼠模型。模型组和罗氟司特组腹膜内注射0.9%的氯化钠和罗氟司特。干预7 d后,对大鼠取样。测定灌洗液中炎症细胞的数量、JAK和STAT-3的蛋白、AST和ALT、IL-6和TNF-α的m RNA表达。结果:在观察的7 d中,正常组大鼠均存活,生存率高于模型组和罗氟司特组(P<0.05),罗氟司特组生存率高于模型组(P<0.05)。与正常组相比,模型组和罗氟司特组术后症状评分均增加(P<0.05),罗氟司特组术后症状评分低于模型组(P<0.05)。模型组和罗氟司特组的mi RNA-218表达低于正常组(P<0.05),而罗氟司特组高于模型组(P<0.05);模型组和罗氟司特组淋巴细胞,中性粒细胞和单核细胞总数,JAK和STAT-3的蛋白质表达,AST、ALT、IL-6和TNF-α水平高于正常组(P<0.05),罗氟司特组上述指标低于模型组(P<0.05)。结论:罗氟司特通过JAK/STAT途径阻断mi RNA-218表达,抑制促炎性细胞因子IL-6和TNF-α的表达,减轻脓毒症炎症的机制和肝脏损害并改善多发性脓毒症的生存率。

Objective:To explore the regulation mechanism of roflumilast on inflammatory factors and lymphocytes in septic inflammatory rats through JAK/STAT pathway.Methods:54 SD mice were randomly divided into normal group(n=18),model group(n=18)and roflumilast group(n=18).The normal group was fed normally,and the model group and roflumilast group were used to establish sepsis model.In the model group and roflumilast group,0.9%sodium chloride and roflumilast were injected intraperitoneally.After 7 days of intervention,the mice were sampled.The number of inflammatory cells,Jak and Stat-3 protein,AST and alt,IL-6 and TNF-αm RNA expression were measured.Results:The survival rate of normal group was higher than that of model group and roflumilast group(P<0.05).The survival rate of roflumilast group was higher than that of model group(P<0.05).Compared with the normal group,the postoperative symptom scores of the model group and the roflumilast group were increased(P<0.05),and the postoperative symptom score of the roflumilast group was lower than that of the model group(P<0.05).The expression of mirna-218 in model group and roflumilast group was lower than that in normal group(P<0.05),while that in roflumilast group was higher than that in model group(P<0.05).The total number of lymphocytes,neutrophils and monocytes,the protein expression of JAK and Stat-3,the levels of AST,alt,IL-6and TNF-αin model group and roflumilast group were higher than those in normal group(P<0.05).The above indexes in roflumilast group were lower than those in model group(P<0.05).Conclusion:Roflumilast blocks the expression of mi RNA-218 through the JAK/STAT pathway,inhibits the expression of pro-inflammatory cytokines IL-6 and TNF-α,reduces the mechanism of sepsis inflammation and liver damage,and improves the development of multiple sepsis survival rate.