游离脂肪酸通过IRE1/XBP1通路调控高甘油三酯血症性急性胰腺炎肾损伤的机制研究  

The mechanism of free fatty acids regulating renal injury via IRE1/XBP1 pathway in hypertriglyceridemic pancreatitis

作　　者：郁蓉 彭云鹏 朱小乐 侯超群 苗毅 李强[1] YU Rong;PENG Yunpeng;ZHU Xiaole;HOU Chaoqun;MIAO Yi;LI Qiang(Pancreas Center,the First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China)

机构地区：[1]南京医科大学第一附属医院胰腺中心,江苏南京210029

出　　处：《南京医科大学学报（自然科学版）》2022年第5期625-631,共7页Journal of Nanjing Medical University(Natural Sciences)

基　　金：江苏高校优势学科建设工程资助项目(JX10231801)。

摘　　要：目的:探讨游离脂肪酸通过IRE1/XBP1通路调控高甘油三酯血症性急性胰腺炎肾损伤的机制。方法:将48只雄性C57BL/6小鼠随机分为对照组(CON组)、重症急性胰腺炎组(SAP组)、高甘油三酯血症性急性胰腺炎组(HTGP组)和CD36抑制剂组(SSO组)。在给予各组小鼠相应处理24 h后,获取小鼠血标本和胰腺、肾组织进行血清学检测、病理学分析及免疫荧光染色。结果:相比SAP组,HTGP组有着较高的甘油三酯和游离脂肪酸水平,且HTGP组的胰腺炎及肾损伤更严重。在HTGP组肾组织中,内质网应激相关的IRE1、XBP1蛋白及介导游离脂肪酸摄取的CD36蛋白的表达水平比在SAP组更高。此外,当给予HTGP组小鼠CD36抑制剂SSO后,SSO组小鼠较HTGP组胰腺及肾损伤减轻,炎症因子水平降低,且肾组织中IRE1、XBP1的表达水平也明显降低。结论:高甘油三酯血症性急性胰腺炎中,CD36介导的游离脂肪酸可激活内质网应激IRE1/XBP1通路调控相关肾损伤。Objective:This study aims to investigate the mechanism of free fatty acids regulating renal injury through IRE1/XBP1pathway in hypertriglyceridemic pancreatitis.Methods:Total 48 male C57BL/6 mice were randomly divided into control group(CON group),severe acute pancreatitis group(SAP group),hypertriglyceridemic pancreatitis group(HTGP group)and CD36 inhibitor group(SSO group).At 24h after corresponding treatment,blood samples,pancreas and kidney tissues were obtained for serological detection,pathological analysis and immunofluorescence staining.Results:Compared with SAP group,HTGP group had higher levels of triglyceride and free fatty acids,and the severity of pancreatitis and renal injury in HTGP group were more severe.In the renal tissues of HTGP group,the expression levels of IRE1 and XBP1 protein related to endoplasmic reticulum stress and CD36 protein which mediated free fatty acid uptake were higher than those in SAP group.Additionally,after administration of CD36 inhibitor in HTGP group,the pancreatic and renal injury,the levels of inflammatory factors and the expression levels of IRE1 and XBP1 in renal tissue decreased significantly in SSO group as compared to HTGP group.Conclusion:In hypertriglyceridemic pancreatitis,CD36mediated free fatty acids may activate endoplasmic reticulum stress through IRE1/XBP1 pathway to regulate related renal injury.

关 键 词：游离脂肪酸 CD36 IRE1 XBP1 内质网应激 高甘油三酯血症性急性胰腺炎 肾损伤 

分 类 号：R657.5[医药卫生—外科学]