白细胞介素33通过调节脂质稳态影响主动脉夹层发生发展  

Interleukin-33 affecting the occurrence and development of aortic dissection by regulating lipid homeostasis

作　　者：汤贺 姜文溪 王雪[1] 王媛[1] Tang He;Jiang Wenxi;Wang Xue;Wang Yuan(Beijing Anzhen Hospital,Capital Medical University,Department of Vascular Biology,Beijing Institute of Heart Lung and Blood Vessel Diseases,Key Laboratory of Remodeling-related Cardiovascular Diseases,Ministry of Education,Collaborative Innovation Center for Cardiovascular Disorders,Beijing 100029,China)

机构地区：[1]首都医科大学附属北京安贞医院、北京市心肺血管疾病研究所心血管生物研究室、教育部重塑相关心血管疾病重点实验室、心血管重大疾病防治协同创新中心,北京100029

出　　处：《中国医药》2023年第4期506-510,共5页China Medicine

基　　金：国家自然科学基金(81870341)。

摘　　要：目的分析白细胞介素33(IL-33)在主动脉夹层(AD)代谢中的血清脂质代谢特征,探讨IL-33治疗AD的可能机制。方法纳入2014年3月至2018年12月在首都医科大学附属北京安贞医院接受开放手术的符合条件的AD住院成年患者25例为AD组,选择同期入院进行健康体检的受试者25例为对照组。同时选用3周龄雄性BALB/c小鼠,分为正常组、模型组和重组蛋白IL-33(rpIL-33)干预组。正常组给予普通饮食,其余小鼠建立AD模型,rpIL-33干预组从喂氨基丙腈富马酸盐的第14天起,每只小鼠腹腔注射rpIL-33100μl,2 mg/L,1次/2 d;模型组以与rpIL-33干预组同样的频率腹腔注射等容积0.9%氯化钠注射液。4周后采集血清和主动脉,主动脉切片观察病理改变。应用超高效液相色谱-串联质谱进行纳入人群和小鼠的靶向脂质代谢组学检测。构建正交偏最小二乘判别分析(OPLS-DA)模型并筛选差异代谢脂质。结果在临床样本中(AD组25例,对照组25例)共检测到420种脂质。基于420种脂质建立OPLS-DA模型(R^(2)=0.977,Q^(2)=0.534),其中334种脂质的变量投影重要度值(VIP)>1。进一步对VIP>1的脂质进行差异分析,共有43种脂质差异有统计学意义(P<0.05),主要包括磷脂酰乙醇胺、二酰甘油和胆固醇脂。rpIL-33干预组小鼠的动脉管腔相对完整圆润,血管病理损伤改善,而模型组小鼠血管内壁弹力板紊乱。与正常组相比,模型组有114种脂质水平改变明显,主要为溶血磷脂酰胆碱、磷脂酰胆碱及胆固醇脂,参与的代谢通路主要为甘油磷脂代谢和鞘脂代谢。与模型组相比,rpIL-33干预组有49种脂质代谢物改变明显,主要为溶血磷脂酸、磷脂酰丝氨酸(40∶4)、磷脂酸(38∶4),参与的代谢通路主要为甘油磷脂代谢。结论IL-33可延缓AD进展,其作用机制可能与调节甘油磷脂代谢有关。Objective To analyze the characteristics of serum lipid metabolism of interleukin-33(IL-33)in aortic dissection(AD)and to explore the possible mechanism of IL-33 in the treatment of AD.Methods From March 2014 to December 2018,25 adult patients with AD who accepted open surgery and met conditions in Beijing Anzhen Hospital,Capital Medical University were included as AD group,and 25 subjects admitted to the hospital for health examination at the same period were selected as the control group.Meanwhile,male BALB/c mice aged 3 weeks were divided into normal group,model group and recombinant protein IL-33(rpIL-33)intervention group.Regular diet were given in the normal group,and AD model was established in other mice.Since the 14th day of feeding aminopropionitrile monofumarate in rpIL-33 intervention group,rpIL-33 was injected intraperitoneally at the dose of 2 mg/L,with 100μl/mouse,once every two days.The model group was injected intraperitoneally with isovolumetric 0.9%sodium chloride injection with same frequency.Four weeks later,serum and aorta were collected,and aortic sections were stained to observe pathological changes.Ultra performance liquid chromatographytandem mass spectrometry was used to detect the targeted lipid metabolomics in human and mice.The differential metabolic lipids were screened by establishing orthogonal partial least square discriminant analysis(OPLS-DA)model.Results A total of 420 lipids were detected in clinical samples(25 cases in AD group,25 cases in control group).The OPLS-DA model was established based on 420 lipids(R^(2)=0.977,Q^(2)=0.534),of which 334 lipids had variable importance in projection(VIP)values>1.Further analysis of the difference of lipids with VIP values>1 showed that there were statistically significant differences in 43 lipids(P<0.05),mainly including phosphatidylethanolamine,diacylglycerol and cholesteryl ester(CE).The arterial lumen of the rpIL-33 intervention group was relatively complete and round,and the vascular pathological injury was improved,while the elas

关 键 词：主动脉夹层 脂质代谢 白细胞介素33 超高效液相色谱-串联质谱 

分 类 号：R543.1[医药卫生—心血管疾病]