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。
Protective Effect of Polysaccharide D from Ophiopogon Japonicus on Inflammatory Bowel Disease in Rats by Activating cAMP/PKA/CREB Signaling Pathway
Objective:To investigate the protective effect of polysaccharide D from Ophiopogon japoni-cus(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 intra-colonic 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-α levels,proportions of Th17 cells and Th17/Treg ratios in peripheral blood,and Bax protein expression were deter-mined.Results:After treatment,compared with the control group,the model group rats showed significant co-lon tissue damage,decreased body weight and colon length,decreased serum IL-10 and cAMP levels,de-creased 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-α levels,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 in-creased,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-α levels 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,possibly by activating the cAMP/PKA/CREB signaling pathway.
Polysaccharide D from ophiopogon japonicuscAMP/PKA/CREB signaling pathwayInflammatory bowel diseaseInflammatory injury
万方数据
维普
