首页|利拉鲁肽对糖尿病心肌病大鼠心功能及心肌代谢异常的改善作用

利拉鲁肽对糖尿病心肌病大鼠心功能及心肌代谢异常的改善作用

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[目的]研究利拉鲁肽对糖尿病心肌病(DCM)大鼠心肌代谢物及相关代谢通路的影响.[方法]3周龄SPF级雄性SD大鼠60只,随机抽取10只作为正常对照组,其余均采用腹腔注射链脲佐菌素联合高糖高脂饮食法建立DCM大鼠模型.DCM造模成功大鼠36只,随机分为DCM模型组(DCM组)、低剂量利拉鲁肽治疗组(LL组)、高剂量利拉鲁肽治疗组(HL组),每组各12只.LL组(100 µg/kg)和HL组(200 µg/kg)分别给予利拉鲁肽腹腔注射,每日一次,干预12周后,经超声心动图检测心功能后麻醉处死大鼠,并取心脏组织进行代谢组学检测,筛选并富集与利拉鲁肽改善DCM大鼠心肌代谢可能有关的差异代谢物及相关通路.[结果]超声结果显示,与正常对照组相比,DCM组左心室射血分数(LVEF)、左心室短轴缩短率(LVFS)显著降低,左心室舒张早期最大血流/二尖瓣心房收缩期最大血流比值(E/A)明显升高(P<0.05).与DCM组相比,LL组和HL组大鼠LVEF、LVFS明显升高,E/A比值显著降低(P<0.05),提示LL组和HL组左心室收缩和舒张功能受损明显减轻.代谢组学检测共发现395种代谢物,其中DCM组与正常对照组、LL组与DCM组、HL组与DCM组各自富集出组间差异代谢物分别为239种、116种、187种,代谢通路分别为13条、6条、20条.以上三组共交集出关键差异代谢物29种,主要涉及3条代谢通路(P<0.05),包括胆碱代谢通路、咖啡因代谢通路以及缬氨酸、亮氨酸和异亮氨酸生物合成通路,其中胆碱代谢通路差异最为显著.[结论]利拉鲁肽可明显改善DCM大鼠心功能及心肌代谢异常,其中胆碱代谢通路可能在利拉鲁肽改善心肌代谢保护心脏功能过程中起到关键作用.
Effect of liraglutide on cardiac dysfunction and myocardial metabolism abnormality in diabetic cardiomyopathy rats
Aim To study the effect of liraglutide on myocardial metabolites and related metabolic pathways in diabetic cardiomyopathy(DCM)rats.Methods Among 60 SPF male SD rats aged 3 weeks,10 rats were randomly selected as normal control group(n=10),and the remaining 50 rats were established by peritoneal injection of streptozoto-cin combined with high-sugar and high-fat diet for DCM rat model.A total of 36 rats were successfully modeled for DCM and randomly divided into DCM model group(DCM group,n=12),low-dose liraglutide treatment group(LL group,n=12)and high-dose liraglutide treatment group(HL group,n=12).Rats in LL group(100 μg/kg)and HL group(200μg/kg)were given intraperitoneal injection of liraglutide once a day.And after 12 weeks of intervention,the rats were killed under anesthesia after echocardiography to detect cardiac function,and the heart tissues were taken for metabolomics detection.The differential metabolites and related pathways that may be related to liraglutide improving myocardial metab-olism in DCM rats were screened and enriched.Results Compared with normal control group,left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)in DCM group were significantly decreased,and the ra-tio of early to late diastolic mitralflow velocities(E/A)was significantly increased(P<0.05).Compared with DCM group,LVEF and LVFS in LL group and HL group were significantly increased,and E/A ratio was significantly decreased(P<0.05),suggesting that the impairment of left ventricular systolic and diastolic function in LL group and HL group was significantly alleviated.395 metabolites were detected by metabolomics,among which 239,116 and 187 different metab-olites and 13,6 and 20 metabolic pathways were enriched in DCM group and normal control group,LL group and DCM group,HL group and DCM group.In the above three groups,29 key differential metabolites were identified related to 3 metabolic pathways including choline metabolic pathway,caffeine metabolic pathway and valine,leucine and isoleucine bi-osynthesis pathway,among which choline metabolic pathway had the most significant differences.Conclusion These results indicated that liraglutide can ameliorate cardiac dysfunction in DCM rats through improving myocardial metabolism in which choline metabolism pathway may play a key role.

diabetic cardiomyopathyliraglutidecardiac functionmyocardial metabolomicscholine met-abolic pathway

朱雅馨、徐瑞霞、张月、渠惠琳、张薇、柳昊睿、王芳、郭远林、李建军

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中国医学科学院北京协和医学院心血管疾病国家重点实验室国家心血管病中心阜外医院心血管代谢中心,北京市 100037

糖尿病心肌病 利拉鲁肽 心功能 心肌代谢组学 胆碱代谢通路

国家自然科学基金项目北京协和医学院协和青年基金

821723343332018200

2024

中国动脉硬化杂志
中国病理生理学会 南华大学

中国动脉硬化杂志

CSTPCD
影响因子:1.086
ISSN:1007-3949
年,卷(期):2024.32(6)