南方医科大学学报

南方医科大学学报 ›› 2022, Vol. 42 ›› Issue (1): 93-100.doi: 10.12122/j.issn.1673-4254.2022.01.11

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虎杖苷减轻大鼠创伤性颅脑损伤后的肠损伤：基于激活Sirt1介导的SOD2和HMGB1去乙酰化抑制氧化应激和炎症反应

秦 娜，黄 林，董 瑞，李 芬，唐叙恒，曾振华，王兴民，杨 翃   

  1. 南方医科大学第三附属医院重症医学科，广东 广州 510630；广东省医学休克微循环重点实验室，广东 广州 510515；南方医科大学南方医院重症医学科，广东 广州 510515；柳州市妇幼保健院病理科，广西 柳州 545001
  • 出版日期:2022-01-20 发布日期:2022-03-02

Polydatin improves intestinal barrier injury after traumatic brain injury in rats by reducing oxidative stress and inflammatory response via activating SIRT1-mediated deacetylation of SOD2 and HMGB1

QIN Na, HUANG Lin, DONG Rui, LI Fen, TANG Xuheng, ZENG Zhenhua, WANG Xingmin, YANG Hong   

  1. Department of Critical Care Medicine, Third Affiliated Hospital of Southern Medical University, Southern Medical University, Guangzhou 510630, China; Guangdong Provincial Key Laboratory of Shock and Microcirculation, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China; Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Department of Pathology, Liuzhou Maternity and Child Healthcare Hospital, Liuzhou 545001, China
  • Online:2022-01-20 Published:2022-03-02

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摘要： 目的 探讨虎杖苷（PD）对创伤性颅脑损伤（TBI）后大鼠肠粘膜损伤的保护作用及其机制。方法 采用液压冲击损伤（FPI）方法用SD大鼠复制TBI动物模型，分别在TBI后12、24、48、72 h收集标本，每组5只；另将大鼠随机分为Sham组（n=5，除了FPI操作其他均进行）、TBI+NS组（n=5，TBI后给予和PD组等容积的生理盐水）和TBI+PD组（n=5，TBI后给予30 mg/kg的PD）。记录大鼠体质量和粪便含水量，观察空肠组织病理，检测D-乳酸（D-LAC）、二胺氧化酶（DAO）、ZO-1和claudin-5水平，测定活性氧自由基（ROS）、过氧化脂质（LPO）和超氧化物岐化酶2（SOD2）含量，检测空肠促炎因子表达水平，检测Sirt1活性，SOD2和HMGB1乙酰化水平。结果 TBI大鼠体质量下降，粪便含水量减少，血清D-LAC、DAO水平进行性升高（P<0.05）。空肠组织损伤加重，ZO-1、claudin-5、SOD2、Sirt1活性明显下降（P<0.05），LPO、ROS、促炎细胞因子、SOD2和HMGB1乙酰化水平增高（P< 0.05）；与TBI+NS组相比，TBI+PD组大鼠体质量恢复，粪便含水量增加，D-LAC和DAO水平降低（P<0.05），空肠组织病理损伤减轻，ZO-1、claudin-5、SOD2表达水平、Sirt1活性增加，ROS、LPO、促炎细胞因子、SOD2和HMGB1乙酰化水平降低（P<0.05）。结论 PD通过激活Sirt1介导的SOD2和HMGB1去乙酰化减轻氧化应激及炎症反应，改善TBI大鼠肠粘膜损伤。

关键词: 创伤性颅脑损伤；Sirt1；虎杖苷；肠粘膜；氧化应激；炎症反应

Abstract: Objective To investigate the protective effect against intestinal mucosal injury in rats following traumatic brain injury (TBI) and explore the underlying mechanism.Methods SD rat models of TBI were established by fluid percussion injury (FPI), and the specimens were collected at 12, 24, 48, and 72 h after TBI. Another 15 rats were randomly divided into sham-operated group (n=5), TBI with saline treatment (TBI+NS) group (n=5), and TBI with PD treatment (TBI+PD) group (treated with 30 mg/kg PD after TBI; n=5). Body weight gain and fecal water content of the rats were recorded, and after the treatments, the histopathology of the jejunum was observed, and the levels of D-lactic acid (D-LAC), diamine oxidase (DAO), ZO-1, claudin-5, and reactive oxygen species (ROS) were detected. Lipid peroxide (LPO) and superoxide dismutase (SOD) 2 content, jejunal pro-inflammatory factors (IL-6, IL-1β, and TNF- α), Sirt1 activity, SOD2 and HMGB1 acetylation level were also determined after the treatments. Results The rats showed significantly decreased body weight and fecal water content and progressively increased serum levels of D-LAC and DAO after TBI (P<0.05) with obvious jejunal injury, significantly decreased expression levels of ZO-1 and claudin-5, lowered SOD2 and Sirt1 activity (P<0.05), increased expression levels of LPO, ROS, and pro-inflammatory cytokines, and enhanced SOD2 and HMGB1 acetylation levels (P<0.05). Compared with TBI+NS group, the rats in TBI+PD group showed obvious body weight regain, increased fecal water content, reduced jejunal pathologies, decreased D-LAC and DAO levels (P<0.05), increased ZO-1, claudin-5, SOD2 expression levels and Sirt1 activity, and significantly decreased ROS, LPO, pro-inflammatory cytokines, and acetylation levels of SOD2 and HMGB1 (P<0.05). Conclusion PD alleviates oxidative stress and inflammatory response by activating Sirt1-mediated deacetylation of SOD2 and HMGB1 to improve intestinal mucosal injury in TBI rats.

Key words: traumatic brain injury; polydatin; Sirt1; intestinal mucosa; oxidative stress; inflammation response