[1]李 刚,陈 茹,马立云,等.利拉鲁肽通过转换生长因子β1/Smad家族成员3信号通路对糖尿病大鼠心肌损伤和肠道菌群的影响[J].陕西医学杂志,2025,54(4):470-474.[doi:DOI:10.3969/j.issn.1000-7377.2025.04.007]
　LI Gang,CHEN Ru,MA Liyun,et al.Effects of Liraglutide on myocardial damage and intestinal flora in diabetic rats through TGF-β1/Smad3 signaling pathway[J].,2025,54(4):470-474.[doi:DOI:10.3969/j.issn.1000-7377.2025.04.007]
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利拉鲁肽通过转换生长因子β1/Smad家族成员3信号通路对糖尿病大鼠心肌损伤和肠道菌群的影响
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《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
54
期数:
2025年4期
页码:
470-474
栏目:
基础研究
出版日期:
2025-04-05

文章信息/Info

Title:
Effects of Liraglutide on myocardial damage and intestinal flora in diabetic rats through TGF-β1/Smad3 signaling pathway
作者:
李 刚1; 陈 茹2; 马立云3; 刘晓艳4 ; 陈 静2
(1.保定市中医院内分泌科,河北 保定071000; 2.唐山市第三医院透析室,河北 唐山 063000; 3.邢台市第一医院神经内科,河北 邢台054000; 4.唐山市丰南区医院内分泌科,河北 唐山063300)
Author(s):
LI Gang1; CHEN Ru2; MA Liyun3; LIU Xiaoyan4; CHEN Jing2
(1.Department of Endocrinology,Baoding Hospital of Traditional Chinese Medicine,Baoding 071000,China; 2.Dialysis Room,The Third Hospital of Tangshan City,Tangshan 063000,China; 3.Department of Neurology,Xingtai First Hospital,Xingtai 054000,China; 4.Department of Endocrinology,Fengnan District Hospital,Tangshan City,Tangshan 063300,China)
关键词:
利拉鲁肽;  糖尿病;  转换生长因子β1/Smad家族成员3信号通路;  心肌损伤;  肠道菌群;  血糖
Keywords:
Liraglutide;  Diabetes mellitus;  TGF-β1/Smad3 signaling pathway;  Myocardial injury;  Intestinal flora;  Blood sugar
分类号:
R 587.1
DOI:
DOI:10.3969/j.issn.1000-7377.2025.04.007
文献标志码:
A
摘要:
目的:探讨利拉鲁肽通过转换生长因子β1(TGF-β1)/Smad家族成员3(Smad3)信号通路对糖尿病大鼠心肌损伤和肠道菌群的影响。方法:选取45只雄性SD大鼠,随机分为对照组、模型组、利拉鲁肽组,以高脂高糖饲料喂养4周后,腹腔注射30 mg/kg链脲佐菌素1次建立大鼠糖尿病模型,每组15只。对照组、模型组以0.1 ml/kg 0.9%氯化钠溶液皮下注射,利鲁拉肽组以0.6 mg/kg利拉鲁肽皮下注射,均1次/d,连续8周。记录干预后各组大鼠体重、空腹血糖、血脂水平及心功能,提取各组大鼠粪便样本,行肠道菌群16s-rDNA测序分析,以苏木精-伊红(HE)染色观察心肌组织结构,蛋白质免疫印迹(Western blot)测心肌中TGF-β1、Smad3和焦亡相关蛋白表达。结果:与模型组比较,利拉鲁肽组体重、空腹血糖及心功能、血脂等各指标均改善,但未优于对照组(均P<0.05)。利鲁拉肽组肠道菌群操作分类单元(OTU)数、丰度的覆盖估计指数(Ace 指数)、总物种丰富度指数(Chao)低于模型组,但高于对照组(均P<0.05)。利拉鲁肽组大鼠肠道拟杆菌(门、目、属)丰度均升高,但低于对照组,高于模型组,厚壁菌(门)、乳杆菌(目、属)丰度均下降,但低于对照组,高于模型组(均P<0.05)。利拉鲁肽组心肌TGF-β1、Smad3、NOD样受体热蛋白结构域3(NLRP3)、凋亡相关的斑点样蛋白(ASC)、天冬氨酸特异性半胱氨酸蛋白酶-1(Caspase-1)蛋白表达均低于模型组,但高于对照组(均P<0.05)。结论:利拉鲁肽可降低DM大鼠血糖,调节肠道菌群,其对心肌损伤的改善作用可能与抑制TGF-β1/Smad3信号通路有关。
Abstract:
Objective:To investigate the effects of liraglutide on myocardial injury and intestinal flora in diabetic rats by transforming the growth factor β1(TGF-β1)/Smad family member 3(Smad3)signaling pathway.Methods:Forty five 45 male SD rats were randomly divided into control group,model group,the lalu peptide group,feed with high fat and sugar after 4 weeks,intraperitoneally injected 30 mg/kg streptozotocin once to establish a rat diabetic model with 15 rats in each group.The control group and model group were subcutaneously injected with 0.1 mL/kg normal saline,and the liraglutide group was subcutaneously injected with 0.6 mg/kg liraglutide,once a day for 8 weeks.After intervention,the body weight,fasting blood glucose,blood lipid levels and cardiac function of rats in each group were recorded.Stool samples of rats in each group were extracted and analyzed by 16s-rDNA sequencing.The myocardial tissue structure was observed by hematoxylin-eosin(HE)staining.The expression of TGF-β1,Smad3 and pyroptosis related proteins in myocardium was measured by Western Blot.Results:Compared with model group,body weight,fasting blood glucose,heart function,blood lipid and other indexes in Liraglutide group were improved,but not better than control group(all P<0.05).The OTU number,Ace index and Chao index of intestinal flora in lirulatide group were lower than those in model group,but higher than those in control group(all P<0.05).The abundance of intestinal Bacteroides(phyla,order and genus)in Liraglutide group was increased,but lower than that in control group and higher than that in model group,and the abundance of firmicutes(phyla)and Lactobacillus(order and genus)was decreased,but lower than that in control group and higher than that in model group(all P<0.05).The protein expressions of TGF-β1,Smad3,NLRP3,ASC and Caspase-1 in Liraglutide group were lower than those in model group,but higher than those in control group(all P<0.05).Conclusion:Liraglutide can reduce blood glucose and regulate intestinal flora in DM rats.The ameliorating effect of liraglutide on myocardial injury in rats may be related to the inhibition of TGF-β1/Smad3 signaling pathway.

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备注/Memo

备注/Memo:
[基金项目]河北省卫生健康委员会医学科学研究计划项目(20201464)
更新日期/Last Update: 2025-04-07