骨化三醇改善早期1型糖尿病大鼠脂质代谢与代谢组学分析  

Calcitriol improves lipid metabolism and metabolomics analysis in early type 1 diabetic rats

作　　者：饶小平 李燕平 陈程 陈洁 舒心 张劼 姚政源 RAO Xiaoping;LI Yanping;CHEN Cheng;CHEN Jie;SHU Xin;ZHANG Jie;YAO Zhengyuan(Key Laboratory of Function and Clinical Transformation of Fujian Universities,Xiamen Medical College,Xiamen,Fujian 361000,China;Department of Basic Medicine,Xiamen Medical College,Xiamen,Fujian 361000,China;Department of Pharmacy,Xiamen Medical College,Xiamen,Fujian 361000,China;Department of Endocrinology,the Second Hospital of Ningbo,Ningbo,Zhejiang 315000,China;School of Public Health,Fujian Medical University,Fuzhou,Fujian 350004,China)

机构地区：[1]厦门医学院,机能与临床转化福建省高校重点实验室,福建厦门361000 [2]厦门医学院,基础医学部,福建厦门361000 [3]厦门医学院,药学系,福建厦门361000 [4]宁波市第二医院内分泌科,浙江宁波315000 [5]福建医科大学公共卫生学院,福建福州350004

出　　处：《安徽医药》2024年第11期2145-2151,共7页Anhui Medical and Pharmaceutical Journal

基　　金：福建省中青年教师教育科研项目(科技类)(JAT220412)。

摘　　要：目的探究骨化三醇喂食对早期1型糖尿病大鼠的改善效果与主要参与的代谢通路影响。方法于2022年3—10月将32只SPF等级SD大鼠采用随机数字表法分为正常对照(Control)组(n=8),模型(T1DM)组(n=12)和治疗(T1DM-Cal)组(n=12),T1DM组与T1DM-Cal组分别在1~4周腹腔注射链脲佐菌素(1次/周)诱导产生1型糖尿病,Control组给予同等体积的柠檬酸缓冲液,T1DM-Cal组从第1周开始每天喂食骨化三醇,T1DM组、Control组给予同等体积的花生油,持续饲养喂食6周后收集血浆样品进行血糖、血脂、脂蛋白酯酶、乙酰乙酸等浓度检测,并以液相色谱-串联质谱(LC-MSMS)进行代谢组学分析。结果与T1DM组相比,T1DM-Cal组的体质量[(326.73±39.86)g比(298.28±39.33)g]及其血浆中的总胆固醇[(1.77±0.28)mmol/L比(1.56±0.22)mmol/L]、高密度脂蛋白[(1.49±0.48)mmol/L比(1.10±0.46)mmol/L]水平显著升高(P<0.05),低密度脂蛋白[(0.17±0.05)mmol/L比(0.23±0.08)mmol/L]、脂蛋白酯酶[(0.23±0.07)mmol/L比(0.34±0.07)mmol/L]、乙酰乙酸[(0.25±0.18)μmol/L比(0.54±0.33)μmol/L]水平显著降低(P<0.05),且均不同程度的接近Control组,而血糖[(18.47±7.36)mmol/L比(19.64±6.16)mmol/L]和三酰甘油[(48.94±10.60)mg/dL比(50.27±14.42)mg/dL]则差异无统计学意义。代谢组学分析结果显示喂食骨化三醇改善了早期1型糖尿病引起的类固醇激素生物合成、初级胆汁酸的生物合成、花生四烯酸代谢、视黄醇代谢等通路的紊乱。结论骨化三醇喂食可改善早期1型糖尿病大鼠血脂组成及反转总胆固醇代谢紊乱,通过影响脂质代谢及调节炎症相关通路而达到一定的治疗效果。Objective To explore the improvement effect of calcitriol feeding on early type 1 diabetic rats and the main metabolic pathways involved.Methods 32 SPF SD rats were randomly divided into Control(n=8),T1DM(n=12)and T1DM-Cal groups(n=12)from March to October 2022.T1DM and T1DM-Cal groups were injected intraperitoneally with Streptozocin(once a week)for 1-4 weeks to induce type 1 diabetes,and the Control group was given the same volume of citrate buffer.The T1DM-Cal group was fed calcitriol every day from the first week,and the T1DM group and Control group were given the same volume of peanut oil.After continuous feeding for six weeks,plasma samples were collected for detection of blood glucose,blood lipid,lipoprotein esterase,acetoacetic acid and other concentrations,and metabolomics analysis was performed by Liquid chromatography-tandem mass spectrometry(LC-MS/MS)method.Results Compared with the T1DM group,the body weight[(326.73±39.86)g vs.(298.28±39.33)g]and plasma total cholesterol[(1.77±0.28)mmol/L vs.(1.56±0.22)mmol/L]and high-density lipoprotein[(1.49±0.48)mmol/L vs.(1.10±0.46)mmol/L]levels of the T1DM-Cal group were significantly increased(P<0.05).The levels of low-density lipoprotein[(0.17±0.05)mmol/L vs.(0.23±0.08)mmol/L],lipoprotein lipase[(0.23±0.07)mmol/L vs.(0.34±0.07)mmol/L]and acetoacetic acid[(0.25±0.18)μmol/L vs.(0.54±0.33)μmol/L]decreased significantly(P<0.05),and they were all close to those of the Control group.There were no significant differences in blood glucose[(18.47±7.36)mmol/L vs.(19.64±6.16)mmol/L]and triglyceride concentrations[(48.94±10.60)mg/dL vs.(50.27±14.42)mg/dL].The results of metabolomics analysis showed that feeding calcitriol improved the disorders of steroid hormone biosynthesis,primary bile acid biosynthesis,arachidonic acid metabolism,retinol metabolism and other pathways caused by early type 1 diabetes.Conclu⁃sions Feeding calcitriol improves blood lipid composition and reverse total cholesterol metabolism disorder in early type 1 diabetic rats.A certa

关 键 词：骨化三醇 维生素D 1型糖尿病 代谢组学 

分 类 号：R587.1[医药卫生—内分泌]