摘要
目的:探讨富辛酸肠内营养对脓毒症急性肝损伤的保护作用及可能机制。方法:首先,将24只SD大鼠随机分为四组:对照组、脓毒症组、脓毒症+肠内营养组、脓毒症+肠内营养+辛酸组,腹腔内注射脂多糖(LPS,5mg/kg)建立内毒血症模型后分别给予3 d肠内营养[100 kcal/(kg·d)]或富辛酸肠内营养[辛酸0.5 g/kg,总能量100kcal/(kg·d)]。肝脏HE染色,生化分析仪检测血清ALT、AST和LDH水平,ELISA检测血清及肝脏IL-6、IL-1β和TNF-α水平,Western blotting检测凋亡相关蛋白Bax、Bcl及Cleaved Caspase-3的表达水平及JNK的活性。其次,将30只SD大鼠随机分为五组:对照组、脓毒症组、脓毒症+肠内营养+辛酸组、脓毒症+肠内营养+辛酸+anisomycin(JNK激活剂)组、脓毒症+SP600125(JNK抑制剂)组。各组腹腔内注射相应的药物并予以相应的营养支持,余处理及检测方法同前。结果:与脓毒症+肠内营养组相比,脓毒症+肠内营养+辛酸组肝脏病理损伤明显好转,肝酶ALT、AST及LDH水平明显下降,肝脏及血清中炎症因子IL-6、IL-1β和TNF-α水平明显下降;下调肝脏中Bax和Cleaved Caspase-3蛋白表达,上调Bcl蛋白表达,抑制JNK的活性。anisomycin显著减弱富辛酸肠内营养对肝脏JNK抑制和抗凋亡的作用及其对脓毒症急性肝损伤的保护作用。SP600125能够显著抑制肝脏JNK活性和凋亡,显示出与富辛酸肠内营养相同的保护脓毒症急性肝损伤的作用。结论:富辛酸肠内营养通过抑制JNK诱导的肝细胞凋亡保护脓毒症急性肝损伤。
Objective: To explore the protective effect of octanoic acid(OA)-rich enteral nutrition(EN) on acute liver injury(ALI) induced by sepsis and the underlying mechanisms. Methods: Twenty-four rats were randomly divided into four groups: sham, lipopolysaccharides(LPS), LPS + EN and LPS + EN + OA groups. In three groups(LPS,LPS + EN and LPS + EN + OA), rats were intraperitoneally injected with LPS(5 mg/kg) to induce endotoxemia. EN and OA-rich EN were then administered in the latter two groups via gastric tube for 3 days, respectively. Liver histopathology, serum liver enzymes, inflammatory cytokines of serum and liver, the expression of liver apoptosis-related protein and JNK activity were measured. Subsequently, another experiment containing five groups [Sham, LPS, LPS +EN + OA, LPS + EN + OA + anisomycin(AN) and LPS + SP600125(SP)](six rats per group) was carried out to evaluate the involvement of JNK in the protective effects of OA-rich EN in sepsis. Results: Compared with the LPS +EN group, OA-rich EN decreased histopathological scores of liver, the levels of liver enzymes and the inflammatory cytokines of serum and liver. OA-rich EN also decreased the expression of Bax and cleaved caspase-3, increased the expression of Bcl and inhibited JNK activity in liver. The protective effect of inhibition of JNK activity and hepatocyte apoptosis conferred by OA-rich EN on ALI was aggravated by AN. Moreover, inhibition of JNK activity conferred by SP inhibited apoptosis and showed the similar effect on ALI compared with the LPS + EN + OA group. Conclusions: OArich EN could alleviate ALI via inhibiting JNK-induced hepatocyte apoptosis during sepsis.
作者
曹春
何凯明
陈伟
杜鹏
CAO Chun;HE Kai-ming;CHEN Wei;DU Peng(Department of General Surgery,The Second Affiliated Hospital of Soochow University,Suzhou 215000,Jiangsu,China)
出处
《肠外与肠内营养》
CAS
CSCD
北大核心
2021年第5期262-266,共5页
Parenteral & Enteral Nutrition
基金
苏州市科技局项目(SYS2019069)
北京清华长庚医院董家鸿院士肝胆胰外科团队(SZYJTD201803)。
关键词
富辛酸肠内营养
脓毒症
急性肝损伤
JNK
凋亡
Octanoic acid-rich enteral nutrition
Sepsis
Acute liver injury
JNK
Apoptosis
