瑞舒伐他汀治疗2型糖尿病动脉粥样硬化共病患者血浆代谢组学研究  

Plasma metabolomics study of simvastatin treatment in patients with type 2 diabetes mellitus and atherosclerosis comorbidity

作　　者：张璐瑶 任中干 刘奎 华传曾 孙培珍 邓涛 员婷 范冬 ZHANG Luyao;REN Zhonggan;LIU Kui;HUA Chuanzeng;SUN Peizhen;DENG Tao;YUAN Ting;FAN Dong(Department of Gastroenterology and Endocrinology,Fuyang Women and Children's Hospital,Fuyang 236500,China;School of Basic Medical Sciences,Fuyang Normal University,Fuyang 236037,China)

机构地区：[1]阜阳市妇女儿童医院消化内分泌科,安徽阜阳236500 [2]阜阳师范大学医学院,安徽阜阳236037

出　　处：《安徽医学》2024年第9期1079-1087,共9页Anhui Medical Journal

基　　金：2021年度阜阳师范大学横向医学研究专项培育项目(编号:2021HXYXZX13);阜阳市自筹经费科技计划项目(编号:FK202081122)。

摘　　要：目的探讨瑞舒伐他汀治疗2型糖尿病动脉粥样硬化共病患者的血浆代谢物变化及可能代谢通路。方法选取2022年11月至2023年6月阜阳市妇女儿童医院消化内分泌科收治的2型糖尿病动脉粥样硬化共病患者30例为研究对象,其中接受瑞舒伐他汀治疗的2型糖尿病动脉粥样硬化共病患者15例为观察组,依据年龄、性别、病程等指标1∶1匹配拒绝使用降脂药物治疗患者15例为对照组,利用液相色谱-质谱联用仪(LC-MS)分析两组患者血浆代谢差异成分,通过无监督主成分分析(PCA)、有监督偏最小二乘法分析(PLS-DA)等多维统计分析,以变量重要性因子>1、差异倍数>1.0和P<0.05为筛选条件筛选差异代谢物,对差异性代谢物进行KEGG通路富集分析。结果与对照组对比,观察组患者治疗30 d后总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)水平均明显改善(P<0.05);两组患者治疗前后TC、TG、LDL-C和HDL-C水平的差值对比,差异有统计学意义(P<0.05)。两组差异代谢产物共290个;正离子模式下筛选出131种差异代谢物,其中上调代谢物89种,下调代谢物42种;负离子模式下筛选出159种差异代谢物,其中上调代谢物125种,下调代谢物34种。KEGG通路分析发现,花生四烯酸代谢,赖氨酸降解,鞘脂代谢,甘油磷脂代谢,丁酸代谢,甘氨酸、丝氨酸和苏氨酸代谢及酪氨酸代谢等7条通路可能为瑞舒伐他汀治疗2型糖尿病动脉粥样硬化共病的潜在作用通路,其中花生四烯酸代谢、赖氨酸降解、鞘脂代谢和甘油磷脂代谢通路最为显著(P均<0.01)。结论瑞舒伐他汀可调节2型糖尿病动脉粥样硬化共病患者血浆代谢物水平,其发挥作用可能与花生四烯酸代谢、赖氨酸降解、鞘脂代谢、甘油磷脂代谢等通路有关。Objective To investigate the plasma differential metabolites and potential mechanisms of action in patients with type 2 dia‑betes mellitus and atherosclerosis comorbidity treated with simvastatin.Methods A prospective case-control study was conducted on 30 pa‑tients with atherosclerosis comorbidities with type 2 diabetes who were admitted to the Department of Gastroendocrinology,Fuyang Women and Children’s Hospital from November 2022 to June 2023,and 15 patients with atherosclerotic comorbidities of type 2 diabetes who received rosu‑vastatin treatment were selected as the observation group.According to age,gender,disease course and other indicators 1∶1,15 patients who re‑fused to use lipid-lowering drugs were matched as the control group.The differences in plasma metabolism between the two groups were ana‑lyzed by liquid chromato-mass spectrometry(LC-MS),and multidimensional statistical analysis was performed by unsupervised principal com‑ponent analysis(PCA)and supervised partial least square analysis(PLS-DA).Differential metabolites were screened with variable importance factor>1,difference factor>1.0 and P<0.05 as screening conditions,and KEGG pathway enrichment analysis was performed for differential metabolites.Results After 30 days of treatment,compared with the control group,the TC,TG,LDL-C,and HDL-C levels of the observation group were significantly improved(P<0.05);the difference in the changes in TC,TG,LDL-C,and HDL-C levels between the two groups before and after treatment was statistically significant(P<0.05).There were 290 different metabolites between the two groups,among which 131 differ‑ential metabolites were selected via positive ion mode,with 89 up-regulated and 42 down-regulated metabolites,and 159 differential metabo‑lites were selected via negative ion mode,with 125 up-regulated and 34 down-regulated metabolites.KEGG pathway analysis revealed that seven pathways,including arachidonic acid metabolism,lysine degradation,sphingolipid metabolism,glycerophospholipid metabolism

关 键 词：瑞舒伐他汀 2型糖尿病 动脉粥样硬化性疾病 血浆 非靶向代谢组学 

分 类 号：R587.1[医药卫生—内分泌] R543.5[医药卫生—内科学]