小儿开胃增食合剂调控SCFAs-FFAR2-IL-18通路关键因子增强厌食症幼龄大鼠机体免疫  

Xiao’er Kaiwei Zengshi(小儿开胃增食)Mixture Improves Immunity of Young Rats with Anorexia by Regulating SCFAs-FFAR2-IL-18 Pathway

作　　者：景姬 李玉霞 何岳珍 张雪 马思淼 JING Ji;LI Yuxia;HE Yuezhen;ZHANG Xue;MA Simiao(Clinical College of Chinese Medicine,Gansu University of Chinese Medicine,Lanzhou 730000;Department of Pediatrics,Affiliated Hospital of Gansu University of Chinese Medicine,Lanzhou 730000)

机构地区：[1]甘肃中医药大学中医临床学院,兰州730000 [2]甘肃中医药大学附属医院儿科,兰州730000

出　　处：《中药药理与临床》2025年第1期70-76,共7页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家自然科学基金(编号:81603660、82160921);甘肃省自然科学基金项目(编号:22JR5RA572)。

摘　　要：目的:观察小儿开胃增食合剂对模型大鼠厌食症发生发展的影响,探讨其基于SCFAs-FFAR2-IL-18通路关键因子治疗小儿厌食症的相关机制。方法:以病因模拟法构建大鼠厌食症模型,记录大鼠摄食量和体质量变化,以双歧杆菌四联活菌片0.405 g/kg组、小儿开胃增食合剂5.7、11.4 g/kg组干预模型,另设正常对照组。6周后采用HE染色检测结肠组织病理变化;气相色谱-质谱联测结肠内容物短链脂肪酸(SCFAs);ELISA法检测血清中的IL-18含量;免疫组化法、Western Blot法和PCR法分别检测结肠组织FFAR2蛋白及mRNA的表达情况;免疫荧光检测大鼠结肠组织NK细胞的表达。结果:与正常对照组相比,模型对照组摄食量和体质量明显下降(P<0.05),黏膜层损伤严重,结肠内容物丙酸、乙酸和丁酸含量升高,结肠组织FFAR2蛋白及mRNA、NK细胞表达上调,血清中IL-18含量升高(P<0.05);与模型对照组相比,小儿开胃增食合剂大鼠进食量和体质量增加,黏膜层结构逐渐趋于清晰完整,结肠内容物丙酸和乙酸含量降低,结肠组织FFAR2蛋白和mRNA、NK细胞表达下调,血清中IL-18含量降低(P<0.05),其中双歧杆菌四联活菌片0.405 g/kg组和小儿开胃增食合剂11.4 g/kg组作用较明显,接近于正常对照组。结论:小儿开胃增食合剂能有效地控制厌食症的发生发展,其作用机制可能是通过SCFAs-FFAR2-IL-18通路关键因子降低炎性细胞因子IL-18和NK的细胞含量,增强机体免疫功能,达到治疗小儿厌食的作用。Objective:To observe the effect of Xiao'er Kaiwei Zengshi(小儿开胃增食)Mixture on the occurrence and development of anorexia and explore the mechanism of the mixture in treating anorexia in children via the short-chain fatty acids(SCFAs)-free fatty acid receptor 2(FFAR2)-interleukin 18(IL-18)pathway.Methods:The rat model of anorexia was established by the etiological simulation method.The changes in food intake and body weight were recorded.Rats were assigned into five groups:control,model,positive control(0.405 g/kg Bifidobacterium Tetravaccine Tablets),and Xiao'er Kaiwei Zengshi Mixture(11.4 g/kg and 5.7 g/kg).The rats were treated for 6 weeks.The colon tissue was stained with hematoxylin-eosin for the observation of pathological changes.The SCFAs in feces were detected by gas chromatography-mass spectrometry.The positive expression,protein level,and mRNA level of FFAR2 in the colon tissue were analyzed by the immunohistochemical assay,Western blotting,and PCR,respectively.The expression of natural killers(NKs)in the colon tissue was detected by immunofluorescence,and the serum level of IL-18 was measure by enzyme-linked immunosorbent assay.Results:Compared with the control group,the model group showed decrease food intake and body weight(P<0.05),seriously damaged mucosal layer,increased content of propionic acid,acetic acid,and butyric acid in feces,upregulated mRNA and protein levels of FFAR2 and expression of NKs in the colon tissue,and elevated serum level of IL-18(P<0.05).Compared with the model group,Xiao'er Kaiwei Zengshi Mixture groups showed increased food intake and body weight,improved mucosal structure,decrease content of propionic acid and acetic acid in feces,downregulated protein and mRNA levels of FFAR2 and expression of NKs in the colon tissue,and lowered IL-18 level in the serum(P<0.05).Particularly,the high-dose Xiao'er Kaiwei Zengshi Mixture and positive control groups showed the indicator levels close to those in the control group.Conclusion:Xiao'er Kaiwei Zengshi Mixture can effectiv

关 键 词：小儿开胃增食合剂 小儿厌食症 短链脂肪酸 游离脂肪酸受体2 白介素-18 

分 类 号：R27[医药卫生—中医学]