罗伊氏乳杆菌ZJ617抑制脂多糖诱导的仔猪肠-肝轴中的炎症和自噬信号通路。

L. reuteri ZJ617 inhibits inflammatory and autophagy signaling pathways in gut-liver axis in piglet induced by lipopolysaccharide.

作者信息

Zhu Tao, Mao Jiangdi, Zhong Yifan, Huang Congxiang, Deng Zhaoxi, Cui Yanjun, Liu Jianxin, Wang Haifeng

机构信息

The Key Laboratory of Molecular Animal Nutrition, Ministry of Education, College of Animal Science, Zhejiang University, Hangzhou, 310058, China.

Xixi Hospital of Hangzhou, Hangzhou, 310023, China.

出版信息

J Anim Sci Biotechnol. 2021 Oct 13;12(1):110. doi: 10.1186/s40104-021-00624-9.

DOI:10.1186/s40104-021-00624-9

PMID:34641957

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8513206/

Abstract

BACKGROUND

This study investigated the protective effects of L. reuteri ZJ617 on intestinal and liver injury and the underlying mechanisms in modulating inflammatory, autophagy, and apoptosis signaling pathways in a piglet challenged with lipopolysaccharide (LPS).

METHODS

Duroc × Landrace × Large White piglets were assigned to 3 groups (n = 6/group): control (CON) and LPS groups received oral phosphate-buffered saline for 2 weeks before intraperitoneal injection (i.p.) of physiological saline or LPS (25 μg/kg body weight), respectively, while the ZJ617 + LPS group was orally inoculated with ZJ617 for 2 weeks before i.p. of LPS. Piglets were sacrificed 4 h after LPS injection to determine intestinal integrity, serum biochemical parameters, inflammatory signaling involved in molecular and liver injury pathways.

RESULTS

Compared with controls, LPS stimulation significantly increased intestinal phosphorylated-p38 MAPK, phosphorylated-ERK and JNK protein levels and decreased IκBα protein expression, while serum LPS, TNF-α, and IL-6 concentrations (P < 0.05) increased. ZJ617 pretreatment significantly countered the effects induced by LPS alone, with the exception of p-JNK protein levels. Compared with controls, LPS stimulation significantly increased LC3, Atg5, and Beclin-1 protein expression (P < 0.05) but decreased ZO-1, claudin-3, and occludin protein expression (P < 0.05) and increased serum DAO and D-xylose levels, effects that were all countered by ZJ617 pretreatment. LPS induced significantly higher hepatic LC3, Atg5, Beclin-1, SOD-2, and Bax protein expression (P < 0.05) and lower hepatic total bile acid (TBA) levels (P < 0.05) compared with controls. ZJ617 pretreatment significantly decreased hepatic Beclin-1, SOD2, and Bax protein expression (P < 0.05) and showed a tendency to decrease hepatic TBA (P = 0.0743) induced by LPS treatment. Pretreatment of ZJ617 before LPS injection induced the production of 5 significant metabolites in the intestinal contents: capric acid, isoleucine 1TMS, glycerol-1-phosphate byproduct, linoleic acid, alanine-alanine (P < 0.05).

CONCLUSIONS

These results demonstrated that ZJ617 pretreatment alleviated LPS-induced intestinal tight junction protein destruction, and intestinal and hepatic inflammatory and autophagy signal activation in the piglets.

摘要

背景

本研究调查了罗伊氏乳杆菌ZJ617对脂多糖（LPS）攻击的仔猪肠道和肝脏损伤的保护作用及其调节炎症、自噬和凋亡信号通路的潜在机制。

方法

将杜洛克×长白×大白仔猪分为3组（每组n = 6）：对照组（CON）和LPS组在腹腔注射（i.p.）生理盐水或LPS（25μg/kg体重）前分别口服磷酸盐缓冲盐水2周，而ZJ617 + LPS组在腹腔注射LPS前口服接种ZJ617 2周。在注射LPS后4小时处死仔猪，以测定肠道完整性、血清生化参数、分子和肝脏损伤途径中涉及的炎症信号。

结果

与对照组相比，LPS刺激显著增加肠道磷酸化-p38 MAPK、磷酸化-ERK和JNK蛋白水平，并降低IκBα蛋白表达，而血清LPS、TNF-α和IL-6浓度（P < 0.05）升高。ZJ617预处理显著抵消了单独LPS诱导的影响，但p-JNK蛋白水平除外。与对照组相比，LPS刺激显著增加LC3、Atg5和Beclin-1蛋白表达（P < 0.05），但降低ZO-1、claudin-3和occludin蛋白表达（P < 0.05），并增加血清DAO和D-木糖水平，这些影响均被ZJ617预处理抵消。与对照组相比，LPS诱导肝脏LC3、Atg5、Beclin-1、SOD-2和Bax蛋白表达显著升高（P < 0.05），肝脏总胆汁酸（TBA）水平显著降低（P < 0.05）。ZJ617预处理显著降低肝脏Beclin-1、SOD2和Bax蛋白表达（P < 0.05），并显示出降低LPS处理诱导的肝脏TBA的趋势（P = 0.0743）。在LPS注射前用ZJ617预处理可在肠内容物中诱导产生5种显著的代谢产物：癸酸、异亮氨酸1TMS、甘油-1-磷酸副产物、亚油酸、丙氨酸-丙氨酸（P < 0.05）。