左归降糖通脉方对糖尿病动脉粥样硬化小鼠短链脂肪酸及G蛋白偶联受体109A的影响  

Effects of Zuogui Jiangtang Tongmai Prescription on Short-chain Fatty Acids and G Protein-coupled Receptor 109A in Diabetic Atherosclerotic Mice

作　　者：陈静 吴琴[1] 张亚男 阳晶晶[1] 陈彦灵 刘武超男 雷芳 李定祥[1] 邓奕辉[1] CHEN Jing;WU Qin;ZHANG Yanan;YANG Jingjing;CHEN Yanling;LIU Wuchaonan;LEI Fang;LI Dingxiang;DENG Yihui(Hunan University of Chinese Medicine,Changsha 410208,China)

机构地区：[1]湖南中医药大学,湖南长沙410208

出　　处：《中国中医药信息杂志》2025年第3期76-82,共7页Chinese Journal of Information on Traditional Chinese Medicine

基　　金：国家重点研发计划(2022YFC3501202);湖南省科技创新团队项目(2020RC4050);湖南省中医药科研计划(E2022010);湖南中医药大学中西医结合一流学科重点项目(2021ZXYJH08)。

摘　　要：目的观察左归降糖通脉方对糖尿病动脉粥样硬化小鼠短链脂肪酸(SCFAs)及G蛋白偶联受体109A(GPR109A)的影响,探讨其改善糖尿病动脉粥样硬化作用机制。方法ApoE^(-/-)小鼠采用高糖高脂饲料喂养联合链脲佐菌素腹腔注射建立糖尿病动脉粥样硬化模型,造模后随机分为模型组、西药组(盐酸二甲双胍+阿托伐他汀)和左归降糖通脉方低、中、高剂量组(19、38、76 g/kg),另设C57BL/6J小鼠为对照组,每组6只,分别予相应溶液灌胃,每日1次,连续4周。检测小鼠血糖,HE染色观察主动脉形态,全自动生化分析仪检测三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)含量,ELISA检测血清糖化血红蛋白(HbA1c)、空腹胰岛素(FINS)、白细胞介素(IL)-1β、IL-6和肿瘤坏死因子(TNF)-α含量,气相色谱法检测肠道SCFAs含量,RT-qPCR和Western blot分别检测回肠组织GPR109A和主动脉组织核因子(NF)-κB p65 mRNA和蛋白表达。结果与对照组比较,模型组小鼠主动脉可见明显斑块和炎性细胞浸润,血糖及血清HbA1c、TG、TC、LDL-C、IL-1β、IL-6、TNF-α含量升高(P<0.01),血清FINS和HDL-C含量降低(P<0.01),肠道乙酸、丙酸、丁酸、异丁酸和异戊酸含量降低(P<0.01),回肠组织GPR109A mRNA和蛋白表达降低,主动脉组织NF-κB p65 mRNA和蛋白表达升高(P<0.01);与模型组比较,各药物组主动脉斑块面积和炎性细胞浸润明显改善,血糖及血清HbA1c、TG、TC、LDL-C、IL-1β、IL-6、TNF-α含量降低(P<0.05,P<0.01),血清FINS和HDL-C含量升高(P<0.05,P<0.01),肠道乙酸、丙酸、丁酸、异丁酸和异戊酸含量升高(P<0.05,P<0.01),回肠组织GPR109A mRNA和蛋白表达升高,主动脉组织NF-κB p65 mRNA和蛋白表达降低(P<0.05,P<0.01)。结论左归降糖通脉方能改善糖尿病动脉粥样硬化小鼠糖脂代谢及炎症反应,其机制可能与调控SCFAs/GPR109A途径有关。Objective To investigate the effects of Zuogui Jiangtang Tongmai Prescription on short-chain fatty acids(SCFAs)and G protein-coupled receptor 109A(GPR109A)in diabetic atherosclerotic mice;To explore its mechanism of improving diabetic atherosclerosis.Methods ApoE^(-/-)mice were fed with high sugar and high fat diet and intraperitoneal injection of streptozotocin to establish atherosclerosis model of diabetes.After modeling,the mice were randomly divided into the model group,Western medicine group(metformin hydrochloride+atorvastatin),and Zuogui Jiangtang Tongmai Prescription low,medium-and high-dosage groups(19,38,76 g/kg);and the other C57BL/6J mice were set as the control group,with 6 mice in each group.Each group was given solution for gavage,once a day for 4 weeks.Blood glucose of the mice were detected,HE staining was used to observe the morphology of the aorta,TG,TC,LDL-C and HDL-C contents were detected by fully automated biochemistry analyzers,ELISA was used to detect the contents of serum HbA1c,fasting insulin(FINS),interleukin(IL)-1β,IL-6 and tumor necrosis factor(TNF)-α,gas chromatography was used to detect the content of intestinal SCFAs,and RT qPCR and Western blot were used to detect the mRNA and protein expressions of GPR109A in ileal tissue and nuclear factor(NF)-κB p65 in aortic tissue,respectively.Results Compared with the control group,obvious plaques and inflammatory cells infiltration were seen in the aorta of the model group,the blood glucose and serum HbA1c,TG,TC,LDL-C,IL-1β,IL-6 and TNFαcontents increased(P<0.01),FINS and HDL-C content decreased(P<0.01),intestinal acetate,propionate,butyric acid,isobutyric acid and isovaleric acid contents decreased(P<0.01),GPR109A mRNA and protein expression in ileal tissue decreased,NF-κB p65 mRNA and protein expression in aortic tissue increased(P<0.01).Compared with the model group,the aortic plaque area and inflammatory cells infiltration were significantly improved in each drug intervention group,the blood glucose and serum HbA1c,TG,TC,LDL-C,IL

关 键 词：左归降糖通脉方 糖尿病动脉粥样硬化 糖脂代谢 炎症反应 SCFAs/GPR109A途径 小鼠 

分 类 号：R285.5[医药卫生—中药学]