基于"肠-菌-屏障"轴探究升清降浊颗粒改善湿阻气滞型慢性功能性便秘及伴随高尿酸血症的作用机制OA
Mechanism of Shengqing Jiangzhuo Granules in ameliorating chronic functional constipation with dampness obstruction and Qi stagnation pattern and associated hyperuricemia based on"gut-microbiota-barrier"axis
该研究通过整合动物药效评价、多组学检测与机制验证,系统考察升清降浊颗粒改善湿阻气滞型慢性功能性便秘及伴随高尿酸血症的药效并阐释其作用机制.首先,采用复合因素造模法建立湿阻气滞型慢性功能性便秘伴随高尿酸血症大鼠模型,设置正常组,模型组,升清降浊颗粒低、中、高剂量组,利那洛肽组,琥珀酸普芦卡必利组,通过检测肠道推进率、组织病理变化、血清胃肠激素[P 物质(SP)、胃动素(MTL)、血管活性肠肽(VIP)]及尿酸和脂代谢指标[总胆固醇(TC)、甘油三酯(TG)],综合评价其药效.进一步结合 16S rDNA 测序与结肠内容物代谢组学分析,解析肠道菌群结构及代谢物谱变化,并通过多组学关联分析,锁定关键调控通路.最后检测结肠组织中缺氧诱导因子-1α(HIF-1α)蛋白及闭锁小带蛋白-1(ZO-1)、闭合蛋白(Occludin)的表达与分布,对相关机制进行验证.结果表明,升清降浊颗粒可显著改善模型大鼠肠道蠕动功能,修复结肠、脾、胃组织损伤,调节胃肠激素紊乱,降低血清尿酸并纠正脂代谢异常.同时,该方能够逆转肠道菌群失调,促进产丁酸盐菌群(如 Faecalibacterium、Blautia)增殖,提升结肠丁酸含量,激活 HIF-1α 信号通路,并增强紧密连接蛋白表达.综上所述,该研究从整体药效到微观机制逐步深入,阐明升清降浊颗粒通过调控"肠道菌群-丁酸盐-HIF-1α-肠道屏障"轴,多靶点、整体性改善湿阻气滞型慢性功能性便秘及伴随高尿酸血症的作用机制,为其临床推广应用提供科学依据.
This study systematically investigated the efficacy and action mechanism of Shengqing Jiangzhuo Granules in ameliorating chronic functional constipation with dampness obstruction and Qi stagnation pattern and associated hyperuricemia by integrating pharmacodynamic evaluation for animals,multi-omics detection,and mechanistic validation.First,a rat model of chronic functional constipation with dampness obstruction and Qi stagnation pattern associated hyperuricemia was established by using a multi-factor modeling method.Animals were divided into a normal group,a model group,Shengqing Jiangzhuo Granules groups with low,medium,and high doses,linagliptin group,and prucalopride succinate group.Intestinal propulsion rate,histopathological changes,serum gastrointestinal hormones[substance P(SP),motilin(MTL),vasoactive intestinal peptide(VIP)],uric acid,and lipid metabolism indicators[total cholesterol(TC),triglycerides(TG)],were detected to comprehensively evaluate the efficacy.Subsequently,16S rDNA sequencing and colonic content metabolomic analysis were performed to delineate changes in gut microbiota structure and metabolite profiles.Through multi-omics correlation analysis,the key regulatory pathways were identified.Finally,the hypoxia-inducible factor-1α(HIF-1α)protein and the distribution/expression of zonula occludens-1(ZO-1)and occludin in colon tissue were detected to verify the relevant mechanism.The results demonstrate that Shengqing Jiangzhuo Granules significantly improve intestinal propulsion of the model rat,repair tissue damage in the colon,spleen,and stomach,regulate gastrointestinal hormone disturbances,reduce uric acid in the serum,and correct lipid metabolism disorders.Moreover,the prescription can reverse gut microbiota dysbiosis,promote the proliferation of butyrate-producing microbiota(e.g.,Faecalibacterium and Blautia),increase colonic butyrate content,activate the HIF-1α signaling pathway,and enhance the expression of tight junction proteins.In conclusion,this study gradually delves from holistic pharmacodynamics to microscopic mechanism,clarifying that the action mechanism of Shengqing Jiangzhuo Granules in exerting a multi-target and holistic improvement effect on chronic functional constipation with dampness obstruction and Qi stagnation pattern,as well as its associated hyperuricemia through regulating the"gut microbiota-butyrate-HIF-1α-intestinal barrier"axis,providing a scientific basis for its clinical popularization and application.
杨怡新;张彦琼;肖自青;马兆臣;胥明珠;卢倩雯;林雅;王萍;许海玉;白长川
福建中医药大学 药学院,福建 福州 350122||中国中医科学院 中药研究所,北京 100700福建中医药大学 药学院,福建 福州 350122||中国中医科学院 中药研究所,北京 100700中国中医科学院 中药研究所,北京 100700中国中医科学院 中药研究所,北京 100700中国中医科学院 中药研究所,北京 100700福建中医药大学 药学院,福建 福州 350122||中国中医科学院 中药研究所,北京 100700福建中医药大学 药学院,福建 福州 350122中国中医科学院 中药研究所,北京 100700辽宁中医药大学,辽宁 大连 116600大连市中医医院,辽宁 大连 116000||辽宁中医药大学 附属第二医院,辽宁 沈阳 110034
升清降浊颗粒湿阻气滞型慢性功能性便秘高尿酸血症"肠道菌群-丁酸盐-HIF-1α-肠道屏障"轴
Shengqing Jiangzhuo Granulesdampness obstruction and Qi stagnation patternchronic functional constipationhype-ruricemia"gut microbiota-butyrate-HIF-1α-intestinal barrier"axis
《中国中药杂志》 2026 (15)
4246-4256,11
国家自然科学基金项目(82574854)中国中医科学院中药研究所技术服务项目(H2024032)
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