文章摘要
饶小平,李燕平,陈程,等.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[J].安徽医药,2024,28(11):2145-2151.
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
  
DOI:10.3969/j.issn.1009-6469.2024.11.006
中文关键词: 骨化三醇  维生素 D  1型糖尿病  代谢组学
英文关键词: Calcitriol  Vitamin D  Type 1 diabetes  Metabonomics
基金项目:福建省中青年教师教育科研项目(科技类)(JAT220412)
作者单位E-mail
饶小平 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
厦门医学院基础医学部福建厦门 361000 
 
李燕平 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
厦门医学院基础医学部福建厦门 361000 
 
陈程 厦门医学院药学系福建厦门 361000  
陈洁 厦门医学院药学系福建厦门 361000  
舒心 厦门医学院药学系福建厦门 361000  
张劼 宁波市第二医院内分泌科浙江宁波 315000  
姚政源 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
厦门医学院基础医学部福建厦门 361000
福建医科大学公共卫生学院福建福州 350004 
201500080004@xmmc.edu.cn 
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中文摘要:
      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。
英文摘要:
      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 feedingfor six weeks, plasma samples were collected for detection of blood glucose, blood lipid, lipoprotein esterase, acetoacetic acid and otherconcentrations, 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 bloodglucose [(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 diabeticrats.A certain therapeutic effect may be achieved by affecting lipid metabolism and regulating inflammation-related pathways.
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