Page 29 - 南京医科大学学报自然科学版

第42卷第5期 南京医科大学学报（自然科学版）
2022年5月 Journal of Nanjing Medical University（Natural Sciences） ·625 ·

·基础研究·

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

郁 蓉，彭云鹏，朱小乐，侯超群，苗 毅，李 强 *

南京医科大学第一附属医院胰腺中心，江苏 南京 210029

［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。
［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
［中图分类号］ R657.5 ［文献标志码］ A ［文章编号］ 1007⁃4368（2022）05⁃625⁃07
doi：10.7655/NYDXBNS20220504

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

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

［Abstract］ Objective：This study aims to investigate the mechanism of free fatty acids regulating renal injury through IRE1 / XBP1
pathway 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，CD36
mediated free fatty acids may activate endoplasmic reticulum stress through IRE1 / XBP1 pathway to regulate related renal injury.
［Key words］ free fatty acids；CD36；IRE1；XBP1；endoplasmic reticulum stress；hypertriglyceridemic pancreatitis；renal injury
［J Nanjing Med Univ，2022，42（05）：625⁃631］

重症急性胰腺炎（severe acute pancreatitis，SAP）
［基金项目］ 江苏高校优势学科建设工程资助项目（JX1023
是胰腺的一种具有高发病率和高死亡率的急性炎
1801）
症性疾病，通常伴有全身炎症反应综合征，甚至多
∗
通信作者（Corresponding author），E⁃mail：liqiang020202@163.
com 器官功能障碍综合征 ［1-2］ 。据报道，在过去十年里，