红芪多糖经SCFAs-GPCRs改善脾气虚型DGP大鼠小肠动力的机制研究  

Study on the mechanism of hedysarum polybotrys polysacchcaide improving small intestinal motility in spleen qi deficiency DGP rats through SCFAs-GPCRs

作　　者：魏昭晖 李荣科[1] 张磊[1] 刘苗 万生芳[1] WEI Zhaohui;LI Rongke;ZHANG Lei;LIU Miao;WAN Shengfang(Gansu University of Chinese Medicine,Lanzhou 730000,China)

机构地区：[1]甘肃中医药大学,兰州730000

出　　处：《中华中医药杂志》2024年第7期3436-3441,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.82060914);中医学一流学科“岐黄英才”导师专项基金;甘肃省优秀博士生项目(No.23JRRA1225);甘肃中医药大学研究生创新项目(No.2022-07)。

摘　　要：目的:观察红芪多糖(HPS)对脾气虚型糖尿病胃轻瘫(DGP)大鼠短链脂肪酸(SCFAs)-G蛋白偶联受体(GPCRs)的影响,探讨HPS改善脾气虚型DGP大鼠小肠动力的可能机制。方法:72只SPF级Wistar雄性大鼠随机分为空白组(10只)和造模组(62只),造模组采用多因素造模法联合小剂量多次腹腔注射链脲佐菌素(STZ)配合高糖高脂饲料不规则喂养法制备脾气虚型DGP大鼠模型,成模大鼠随机分为模型组,阳性对照组(二甲双胍片0.09g·kg·d^(-1)),HPS高、中、低剂量组(0.2、0.1、0.05g·kg·d^(-1)),空白组与模型组给予等量纯水灌胃,每天1次,连续8周。观察大鼠随机血糖、小肠推进率;光镜下观察小肠病理形态学改变;ELISA法检测血清中胰高血糖素样肽-1(GLP-1)、肽YY(PYY)、5-羟色胺(5-HT)含量,RT-PCR及Western Blot分别检测回肠组织中G蛋白偶联受体(GPR)41、GPR43、GPR109A mRNA及蛋白表达水平;气相色谱法测定粪便中SCFAs含量。结果:与空白组比较,模型组随机血糖和PYY、GLP-1含量显著上升(P<0.01,P<0.05),小肠推进率、5-HT含量显著下降(P<0.01);光镜下小肠组织正常结构被破坏,肠绒毛消失,肠腺变性坏死;乙酸、丁酸、丙酸含量及GPR41、GPR43、GPR109A mRNA及蛋白表达显著下降(P<0.01,P<0.05)。用药8周后,与模型组比较,阳性对照组、HPS高剂量组随机血糖、PYY、GLP-1含量显著下降(P<0.01),小肠推进率、5-HT含量显著升高(P<0.01);光镜下各给药组情况好转,其中以HPS高、中剂量组好转明显;乙酸、丙酸、丁酸含量及GPR41、GPR43、GPR109A mRNA及蛋白表达显著升高(P<0.01,P<0.05)。与阳性对照组比较,HPS低剂量组小肠组织中GPR41、GPR43、GPR109A mRNA及蛋白表达显著降低(P<0.01,P<0.05)。结论:HPS改善脾气虚型DGP大鼠小肠动力的机制可能与提高SCFAs-GPCRs含量,改善肠道内稳态有关。Objective:To observe the effect of hedysarum polybotrys polysacchcaide(HPS)on short chain fatty acids(SCFAs)-G protein-coupled receptors(GPCRs)in rats with spleen qi deficiency type diabetes gastroparesis(DGP),and to explore the possible mechanism of HPS in improving intestinal motility in rats with spleen qi deficiency type DGP.Methods:A total of 72 SPF grade Wistar male rats were randomly divided into a blank group of 10 rats and model group of 62 rats.The modeling group used a multifactor modeling method combined with low dose multiple intraperitoneal injections of STZ and irregular feeding with high sugar and high fat feed to prepare a spleen qi deficiency type DGP rat model.The modeling rats were randomly divided into a model group,a positive control group(0.09 g kg·kg·d^(-1)Meformin Tablets),and high,medium,and low dose HPS groups(0.2,0.1,0.05 g·kg·d^(-1)),the blank group and model group were given equal doses of pure water by gavage once a day for 8 consecutive weeks.The random blood glucose and small intestine propulsion rate of rats were observed.The pathological and morphological changes of the small intestine under light microscopy were observed,ELISA method was used to detect the levels of GLP-1,PYY and 5-HT in serum,while RTPCR and Western Blot were used to detect the mRNA and protein expression levels of GPR41,GPR43 and GPR109A in small intestine tissue;gas chromatography was used to determine the content of SCFAs in feces.Results:Compared with the blank group,the model group showed an increase in random blood glucose,PYY and GLP-1 levels(P<0.01,P<0.05),while the small intestine propulsion rate and 5-HT content decreased(P<0.01);Under light microscopy,the normal structure of small intestine tissue was destroyed,intestinal villi disappeared,intestinal glands degenerated and necrotic,and the content of acetic acid,butyric acid,propionic acid,GPR41,GPR43,GPR109A mRNA and protein expression decreased(P<0.01,P<0.05).After 8 weeks of medication,compared with the model group,the positive control group

关 键 词：糖尿病胃轻瘫 红芪多糖 G蛋白偶联受体 短链脂肪酸 肠动力 机制 动物模型 

分 类 号：R285.5[医药卫生—中药学]