基于p38MAPK信号通路探讨八月札提取物对肝郁脾虚证大鼠结肠免疫功能的影响  

Akebiae Fructus Extract Improves Colonic Immune Function in Rats with Syndrome of Liver Depression and Spleen Deficiency via p38MAPK Signaling Pathway

作　　者：谢慧臣 罗丽华 王宏伟 周家全 XIE Hui-chen;LULi-hua;WANG Hong-wei;Zhou Jia-quan(Hubei Minzu University,Enshi Hubei 445000;The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture,Enshi Hubei 445000)

机构地区：[1]湖北民族大学,湖北恩施445000 [2]恩施自治州中心医院,湖北恩施445000

出　　处：《世界中西医结合杂志》2023年第12期2339-2343,共5页World Journal of Integrated Traditional and Western Medicine

基　　金：湖北省教育厅科学研究计划指导性项目(B2015100)。

摘　　要：目的探讨八月札提取物对肝郁脾虚证大鼠结肠组织免疫功能及对p38MAPK信号通路的影响,阐明民族药八月札改善肝郁脾虚证候的药理作用机制。方法将60只雄性SD大鼠按随机数字表法分为正常组、肝郁脾虚证模型组(以下简称模型组)、八月札高、中、低剂量组、盐酸舍曲林组,每组10只。除正常组外的五组均以慢性束缚、过度疲劳、苦寒破气加饥饱失常法复制肝郁脾虚模型,造模时间为21 d。造模完成后,各治疗组每天按相应剂量药物灌胃治疗,共计14 d。治疗期满后观察比较各组大鼠脾及胸腺指数,检测结肠组织IL-6、INF-γ、IL-2、IL-13含量,结肠组织细胞中P38蛋白激酶(p38MAPK),有丝分裂原和应激活化型蛋白激酶1(MSK1)蛋白和基因表达。结果模型大鼠造模结束时,与模型组比较,八月札高、中、低剂量组及盐酸舍曲林组胸腺指数升高,脾指数明显下降,结肠组织IL-6、INF-γ含量降低,IL-2、IL-13含量明显升高;结肠细胞中p38MAPK,MSK1蛋白及基因表达水平明显降低,差异均有统计学意义(P<0.05)。结论八月札提取物可通过调节结肠组织细胞免疫相关因子的表达及对p38MAPK相关信号通路进行干预,修复肝郁脾虚证大鼠受损的结肠组织结构。Objective To investigate the effects of Akebiae Fructus extract on the immune function and p38MAPK signaling pathway in the colon tissue of rats with the syndrome of liver depression and spleen deficiency,and to elucidate the pharmacological mechanism of Akebiae Fructus extract in mitigating the syndrome.Methods Sixty male SD rats were randomized into normal,model(syndrome of liver depression and spleen deficiency),high-,medium-,and low-dose Akebiae Fructus extract,and sertraline hydrochloride groups(n=10).The rats in other groups except the normal group were exposed to chronic restraint,excessive fatigue,cold medicines for qi stagnation combined with hunger and satiation disorder for 21 days for the modeling of liver depression and spleen deficiency.After the modeling,rats were administrated with corresponding doses of drugs by gavage every day for 14 days.After treatment,spleen and thymus indexes and colonic histopathological changes were observed,and the content of interleukin(IL)-6,interferon(INF)-γ,IL-2,and IL-13 in the colonic tissue was measured.The mRNA and protein levels of P38 mitogen-activated protein kinase(p38MAPK)and mitogen-and stress-activated protein kinase 1(MSK1)in the colon cells were determined.Results Compared with the model group,different doses of Akebiae Fructus extract and sertraline hydrochloride increased the thymus index,decreased the spleen index,lowered the IL-6 and INF-γlevels and elevated the IL-2 and IL-13 levels in the colon tissue,and down-regulated the mRNA and protein levels of p38MAPK and MSK1 protein in colon cells(all P<0.05).Conclusion By regulating the expression of cellular immune function-related cytokines in the colon tissue and the p38MAPK signaling pathway,Akebiae Fructus extract can repair the damaged colon tissue and comprehensively mitigate the symptoms related to spleen deficiency.

关 键 词：八月札提取物 肝郁脾虚 病理结构 免疫功能 脑-肠轴 丝裂原活化蛋白激酶 信号通路 

分 类 号：R285.5[医药卫生—中药学]