摘要
目的探讨小儿开胃增食合剂治疗厌食症的可能作用机制。方法采用病因模拟法建立厌食症大鼠模型,空白组正常饲养。造模成功后随机分为模型组、中药组(小儿开胃增食合剂,11.4 g/kg)、益生菌组(双歧杆菌四联活菌片,0.405 g/kg),进行相应干预28 d。记录大鼠体质量和摄食量变化,液相色谱-质谱技术测定回肠内容物胆汁酸含量,PCR和Western blot检测回肠组织法尼醇X受体(FXR)、成纤维细胞生长因子(FGF)15/19 mRNA及蛋白表达,ELISA检测血清FGF15/19含量,免疫组化染色检测下丘脑组织FGF15/19阳性表达,免疫荧光染色检测下丘脑组织刺鼠相关蛋白/神经肽Y(AgRP/NPY)神经元表达。结果与空白组比较,模型组大鼠摄食量、体质量显著减少(P<0.05),回肠内容物12-酮基石胆酸含量显著升高(P<0.05),回肠组织FXR、FGF15/19 mRNA及蛋白表达显著升高(P<0.05),血清FGF15/19含量显著升高(P<0.05),下丘脑FGF15/19阳性表达显著升高(P<0.05),AgRP/NPY神经元表达显著降低(P<0.05);与模型组比较,中药组和益生菌组大鼠摄食量、体质量显著增加(P<0.05),中药组回肠内容物胆酸、牛磺胆酸钠盐、牛磺-β-鼠胆酸钠盐、牛磺猪去氧胆酸+牛磺熊去氧胆酸含量显著降低(P<0.05),回肠组织FXR、FGF15/19 mRNA及蛋白表达显著下降(P<0.05),血清FGF15/19含量显著降低(P<0.05),下丘脑FGF15/19阳性表达显著降低(P<0.05),AgRP/NPY神经元表达显著升高(P<0.05)。结论小儿开胃增食合剂可调控胆汁酸-FXR-FGF15/19信号通路关键分子表达,降低对AgRP/NPY神经元的抑制,改善大鼠厌食症状,从而治疗小儿厌食症。
Objective To explore the possible mechanism of Xiaoer Kaiwei Zengshi Mixture in treating anorexia.Methods The anorexia rat model was established by the etiological simulation method,the control group was raised normally.The modeled rats were randomly divided into model group,TCM group(Xiaoer Kaiwei Zengshi Mixture,11.4 g/kg)and probiotic group(Bifidobacterium Bifidum Tetragonum tablets,0.405 g/kg)under corresponding intervention for 28 days.The body mass and food intake of the rats were recorded,bile acids in ileal contents were quantitatively determined by liquid chromatography-mass spectrometry technique,the expressions of FXR,FGF15/19 mRNA and protein in ileal tissue were detected by PCR and Western blot,ELISA was used to detect the FGF15/19 content in serum,positive expression of FGF15/19 in hypothalamic tissue was detected by immunohistochemical staining,the expression of AgRP/NPY neurons in hypothalamic was detected by immunofluorescence.Results Compared with the blank group,the intake and body mass of rats in the model group were significantly reduced(P<0.05),the content of 12-keto cholic acid in ileal contents significantly increased(P<0.05),the mRNA and protein expressions of FXR and FGF15/19 in ileum significantly increased(P<0.05),the content of FGF15/19 in serum significantly increased(P<0.05),the positive expression of FGF15/19 in hypothalamus significantly increased(P<0.05),and the expression of AgRP/NPY neurons significantly decreased(P<0.05).Compared with the model group,the intake and body mass of the rats in TCM group and probiotic group were significantly elevated(P<0.05),the contents of cholic acid,sodium taurocholate,sodium taurocholate-β-mouse bile acid,taurochlorodeoxycholic acid+taurochlorodeoxycholic acid in ileal contents of TCM group significantly decreased(P<0.05),the expressions of FXR and FGF15/19 mRNA and protein in ileal tissue significantly decreased(P<0.05),the content of FGF15/19 in serum significantly decreased(P<0.05),the positive expression of FGF15/19 in hypothalamus significantly decreased(P<0.05),and the expression of AgRP/NPY neurons significantly increased(P<0.05).Conclusion Xiaoer Kaiwei Zengshi Mixture can regulate the expressions of key factors in the bile acids-FXR-FGF15/19 signaling pathway,reduce inhibition of AgRP/NPY neurons,and improve the symptoms of anorexia in rats,so as to treat infantile anorexia.
作者
崔敏
李玉霞
何岳珍
田文霞
陈静
刘青灵
孙铭阳
CUI Min;LI Yuxia;HE Yuezhen;TIAN Wenxia;CHEN Jing;LIU Qingling;SUN Mingyang(School of Clinical Chinese Medicine,Gansu University of Chinese Medicine,Lanzhou 730000,China;Affiliated Hospital of Gansu University of Chinese Medicine,Lanzhou 730000,China;The First Hospital of Lanzhou University,Lanzhou 730000,China)
出处
《中国中医药信息杂志》
2026年第4期72-79,共8页
Chinese Journal of Information on Traditional Chinese Medicine
基金
国家自然科学基金(82160921)
第五批全国中医临床优秀人才研修项目(2022年)
甘肃省科技厅自然科学基金(24JRRA551、25JRRA1010)。
