麦冬皂苷D调节cAMP/PKA/CREB信号通路对炎症性肠病大鼠炎性损伤的影响  

Protective Effect of Polysaccharide D from Ophiopogon Japonicus on Inflammatory Bowel Disease in Rats by Activating cAMP/PKA/CREB Signaling Pathway

作　　者：朱曙光[1] 李曙晖[1] 陈鹏[1] 徐大恒 ZHU Shuguang;LI Shuhui;CHEN Peng(Tengzhou Central People's Hospital,Shandong Tengzhou 277500,China)

机构地区：[1]山东省滕州市中心人民医院消化内科,山东滕州277500

出　　处：《河北医学》2024年第5期781-787,共7页Hebei Medicine

基　　金：山东省医药卫生科技发展计划项目,(编号:2017WS251)。

摘　　要：目的:探究麦冬皂苷D调节cAMP/PKA/CREB信号通路对炎症性肠病(IBD)大鼠炎性损伤的影响。方法:将大鼠分为对照组、模型组、麦冬皂苷D低剂量组、麦冬皂苷D高剂量组和麦冬皂苷D高剂量+H-89(cAMP抑制剂)组。检测大鼠质量和大鼠结肠长度;酶联免疫吸附法检测血清IL-17、IL-6、IL-10、TNF-α、cAMP水平;流式细胞术检测大鼠外周血中Th17、Treg细胞比例;HE染色检测结肠组织病理损伤;Western blot检测大鼠结肠组织中Bax、Bcl-2以及cAMP/PKA/CREB信号通路相关蛋白表达。结果:治疗结束后,与对照组相比,模型组大鼠结肠组织显著损伤,体质量、结肠长度、血清IL-10、cAMP水平、外周血Treg细胞比例、结肠组织Bcl-2、p-PKA/PKA、p-CREB/CREB蛋白表达显著降低,血清IL-17、IL-6、TNF-α水平、外周血中Th17比例和Th17/Treg比值、Bax蛋白表达显著升高(P<0.05);与模型组相比,麦冬皂苷D低、高剂量组大鼠结肠组织显著减轻,体质量、结肠长度、血清IL-10、cAMP水平、外周血Treg细胞比例、结肠组织Bcl-2、p-PKA/PKA、p-CREB/CREB蛋白表达显著升高,血清IL-17、IL-6、TNF-α水平、外周血中Th17比例和Th17/Treg比值、Bax蛋白表达显著降低(P<0.05);H-89可部分逆转麦冬皂苷D对炎症性肠病大鼠的治疗作用(P<0.05)。结论:麦冬皂苷D可降低IBD大鼠炎症反应和结肠组织损伤,可能是通过激活cAMP/PKA/CREB信号通路实现的。Objective:To investigate the protective effect of polysaccharide D from Ophiopogon japonicus(MCD)on inflammatory bowel disease(IBD)in rats and its potential mechanism.Methods:Male SD rats were randomly divided into 5 groups:control group,model group,MCD low-dose group(50 mg/kg·d),MCD high-dose group(100 mg/kg·d),and MCD+H-89 group(100 mg/kg·d MCD+5 mg/kg·d H-89).The model group was induced by 2,4-dinitrochlorobenzene(DNCB)sensitization and repeated intracolonic administration of DSS.The treatment groups were given MCD or MCD+H-89 for 28 days.Body weight,colon length,serum IL-10,cAMP levels,proportions of Treg cells in peripheral blood,expressions of Bcl-2,p-PKA/PKA,p-CREB/CREB proteins in colon tissues,serum IL-17,IL-6,TNF-αlevels,proportions of Th17 cells and Th17/Treg ratios in peripheral blood,and Bax protein expression were determined.Results:After treatment,compared with the control group,the model group rats showed significant colon tissue damage,decreased body weight and colon length,decreased serum IL-10 and cAMP levels,decreased proportions of Treg cells in peripheral blood,decreased expressions of Bcl-2,p-PKA/PKA,p-CREB/CREB proteins in colon tissues,increased serum IL-17,IL-6,TNF-αlevels,increased proportions of Th17 cells and Th17/Treg ratios in peripheral blood,and increased Bax protein expression(P<0.05).Compared with the model group,the colon tissues of rats in the MCD low-dose and high-dose groups were significantly alleviated,body weight and colon length were increased,serum IL-10 and cAMP levels were increased,proportions of Treg cells in peripheral blood were increased,expressions of Bcl-2,p-PKA/PKA,p-CREB/CREB proteins in colon tissues were increased,serum IL-17,IL-6,TNF-αlevels were decreased,proportions of Th17 cells and Th17/Treg ratios in peripheral blood were decreased,and Bax protein expression was decreased(P<0.05).H-89 could partially reverse the therapeutic effect of MCD on IBD rats(P<0.05).Conclusion:MCD can reduce the inflammatory response and colon tissue damage in IBD rats,

关 键 词：麦冬皂苷D cAMP/PKA/CREB信号通路 炎症性肠病 炎性损伤 

分 类 号：R285.5[医药卫生—中药学]