参苓白术散调控菌群代谢相关蛋白和TLR4/NF-κB/NLRP3炎症轴改善溃疡性结肠炎的机制研究OA
Mechanism of Shenling baizhu san in ameliorating ulcerative colitis via regulating flora metabolism-related proteins and TLR4/NF-κB/NLRP3 inflammatory axis
目的 研究参苓白术散(SLBZS)改善溃疡性结肠炎(UC)的作用机制.方法 将小鼠随机分为正常组、模型组及SLBZS低、中、高剂量组(3、6、12 g/kg),每组10只.除正常组外,其余各组小鼠自由饮用3%葡聚糖硫酸钠溶液7 d,以诱导UC模型.在造模的同时,各组小鼠灌胃相应药液/双蒸水,每日1次,连续7 d.末次给药后,观察小鼠结肠组织病理形态学变化,检测血清中炎症因子[肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)、IL-18]水平,检测肝脏、胆囊、结肠组织中总胆汁酸含量,检测结肠组织中NOD样受体热蛋白结构域相关蛋白3(NLRP3)表达水平,检测肝脏/结肠组织中菌群代谢相关蛋白[G蛋白偶联受体41(GPR41)、GPR43、法尼醇X受体(FXR)、G蛋白偶联胆汁酸受体1(TGR5)、黄素单加氧酶3(FMO3)、细胞色素P450家族27亚家族A成员1(CYP27A1)、CYP7A1]和Toll样受体4(TLR4)/核因子κB(NF-κB)/NLRP3炎症轴相关蛋白[TLR4、NF-κB、磷酸化NF-κB(p-NF-κB)、髓样分化因子88(MyD88)、NLRP3、凋亡相关斑点样蛋白(ASC)、胱天蛋白酶1(caspase-1)]表达水平.结果 与模型组相比,SLBZS中、高剂量组小鼠结肠组织损伤程度减轻,炎症细胞浸润减少;血清中TNF-α、IL-1β、IL-18水平,肝脏、结肠中总胆汁酸含量,肝脏组织中FMO3、CYP7A1和结肠组织中TLR4、p-NF-κB、NF-κB、MyD88、NLRP3、ASC、caspase-1的蛋白表达水平均显著降低(P＜0.05);胆囊中总胆汁酸含量以及结肠组织中GPR41、GPR43和肝脏组织中CYP27A1、FXR、TGR5的蛋白表达水平均显著升高(P＜0.05).结论 SLBZS可能通过调控菌群代谢相关蛋白表达、抑制TLR4/NF-κB/NLRP3炎症轴异常激活,减轻结肠炎症损伤,从而改善UC病理状态.
OBJECTIVE To investigate the mechanism of Shenling baizhu san(SLBZS)in ameliorating ulcerative colitis(UC).METHODS Mice were randomly divided into normal group,model group,and low-,medium-,high-dose SLBZS groups(3,6,12 g/kg),with 10 mice in each group.Except for the normal group,mice in other groups were given free access to 3%dextran sulfate sodium solution for 7 days to establish UC models.Simultaneously,mice in each group were intragastrically administered corresponding medicinal liquid or double-distilled water once a day for consecutive 7 days.After the last administration,the histopathological morphology of colon tissues was observed;the serum levels of inflammatory factors including tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and IL-18 were detected;the total bile acid contents in liver,gallbladder and colon tissues were determined;the expression level of NOD-like receptor family pyrin domain-containing protein 3(NLRP3)in colon tissues was tested.The expression levels of flora metabolism-related proteins[G protein-coupled receptor 41(GPR41),GPR43,farnesoid X receptor(FXR),G protein-coupled bile acid receptor 1(TGR5),flavin-containing monooxygenase 3(FMO3),cytochrome P450 family 27 subfamily A member 1(CYP27A1),CYP7A1]in liver or colon tissues,as well as the proteins related to Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB)/NLRP3 inflammatory axis[TLR4,NF-κB,phosphorylated NF-κB(p-NF-κB),myeloid differentiation factor 88(MyD88),NLRP3,apoptosis-associated speck-like protein containing a CARD(ASC),caspase-1]in colon tissues were measured.RESULTS Compared with the model group,the colon tissue injury and inflammatory cell infiltration were alleviated in medium-and high-dose SLBZS groups.The serum levels of TNF-α,IL-1β and IL-18,total bile acid contents in liver and colon tissues,as well as the protein expression levels of FMO3 and CYP7A1 in liver tissues,TLR4,p-NF-κB,NF-κB,MyD88,NLRP3,ASC and caspase-1 in colon tissues were significantly decreased(P＜0.05).Meanwhile,the total bile acid content in gallbladder,the protein expression levels of GPR41 and GPR43 in colon tissues,along with CYP27A1,FXR and TGR5 in liver tissues were significantly increased(P＜0.05).CONCLUSIONS SLBZS may relieve colonic inflammatory injury and ameliorate UC by regulating the expression of flora metabolism-related proteins and inhibiting the abnormal activation of TLR4/NF-κB/NLRP3 inflammatory axis.
徐佳佳;韩飞;游宇;王佼曼;刘玉晖;常诗瑶;贺智贤;李萍;王紫嫣;熊魏
江西中医药大学药学院,南昌 330004江西中医药大学药学院,南昌 330004||江西中医药大学药学院中药药效物质基础江西省重点实验室,南昌 330004南昌大学第一附属医院消化内科,南昌 330006江西中医药大学国际教育学院,南昌 330004江西中医药大学药学院,南昌 330004江西中医药大学药学院,南昌 330004江西中医药大学药学院,南昌 330004江西中医药大学药学院,南昌 330004江西中医药大学药学院,南昌 330004江西中医药大学药学院,南昌 330004
医药卫生
参苓白术散溃疡性结肠炎TLR4/NF-κB/NLRP3炎症轴肠道菌群胆汁酸代谢
Shenling baizhu sanulcerative colitisTLR4/NF-κB/NLRP3 inflammatory axisintestinal florabile acid metabolism
《中国药房》 2026 (15)
1992-1997,6
江西省自然科学基金面上项目(No.20232BAB206169)江西省自然科学基金重点项目(No.20232ACB206058,No.20232ACB206064)江西省中医药管理局科技计划项目(No.2024B0037)江西省研究生创新专项资金项目(No.YC2025-S208)
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