罗伊氏乳杆菌 ZJ617 培养上清液减轻脂多糖诱导的小鼠急性肝损伤。
Lactobacillus reuteri ZJ617 Culture Supernatant Attenuates Acute Liver Injury Induced in Mice by Lipopolysaccharide.
机构信息
College of Animal Science, MOE Key Laboratory of Molecular Animal Nutrition, Zhejiang University, Hangzhou, China.
Institute of Animal Nutrition, College of Animal Science and Technology, Zhejiang A&F University, Lin'an, China.
出版信息
J Nutr. 2019 Nov 1;149(11):2046-2055. doi: 10.1093/jn/nxz088.
BACKGROUND
Lactobacillus rhamnosus GG culture supernatant (LGGs) promotes intestinal integrity and ameliorates acute liver injury induced by alcohol in mice.
OBJECTIVES
The aim of this study was to investigate the protective effects and molecular mechanisms of Lactobacillus reuteri ZJ617 culture supernatant (ZJ617s) on acute liver injury induced by lipopolysaccharide (LPS) in mice.
METHODS
Male C57BL/6 mice (20 ± 2 g, 8 wk old) were randomly divided into 4 groups (6 mice/group): oral inoculation with phosphate-buffered saline (control), intraperitoneal injection of LPS (10 mg/kg body weight) (LPS), oral inoculation with ZJ617s 2 wk before intraperitoneal injection of LPS (ZJ617s + LPS), or oral inoculation with LGGs 2 wk before intraperitoneal injection of LPS (LGGs + LPS). Systemic inflammation, intestinal integrity, biomarkers of hepatic function, autophagy, and apoptosis signals in the liver were determined.
RESULTS
Twenty-four hours after LPS injection, the activities of serum alanine transaminase and aspartate transaminase were 32.2% and 30.3% lower in the ZJ617s + LPS group compared with the LPS group, respectively (P < 0.05). The ZJ617s + LPS group exhibited higher intestinal expression of claudin 3 (62.5%), occludin (60.1%), and zonula occludens 1 (60.5%) compared with the LPS group (P < 0.05). The concentrations of hepatic interleukin-6 and tumor necrosis factor-α were 21.4% and 27.3% lower in the ZJ617s + LPS group compared with the LPS group, respectively (P < 0.05). However, the concentration of interleukin-10 was 22.2% higher in the ZJ617s + LPS group. LPS increased the expression of Toll-like receptor 4 (TLR4; by 50.5%), phosphorylation p38 mitogen-activated protein kinase (p38MAPK; by 57.1%), extracellular signal-regulated kinase (by 77.8%), c-Jun N-terminal kinase (by 42.9%), and nuclear factor-κB (NF-κB; by 36.0%) compared with the control group. Supplementation with ZJ617s or LGGs ameliorated these effects (P < 0.05). Moreover, the hepatic expression of active caspase-3 and microtubule-associated protein 1 light chain 3 II was 23.8% and 28.6% lower in the ZJ617s + LPS group compared with the LPS group, respectively (P < 0.05).
CONCLUSIONS
ZJ617s exerts beneficial effects on the mouse liver through suppression of hepatic TLR4/MAPK/NF-κB activation, apoptosis, and autophagy. This trial was registered at Zhejiang University (http://www.lac.zju.edu.cn) as NO.ZJU20170529.
背景
鼠李糖乳杆菌 GG 培养上清液（LGGs）可促进肠道完整性，并改善酒精诱导的小鼠急性肝损伤。
目的
本研究旨在探讨罗伊氏乳杆菌 ZJ617 培养上清液（ZJ617s）对脂多糖（LPS）诱导的小鼠急性肝损伤的保护作用及其分子机制。
方法
雄性 C57BL/6 小鼠（20±2 g，8 周龄）随机分为 4 组（每组 6 只）：口服磷酸盐缓冲液（对照）、腹腔注射 LPS（10 mg/kg 体重）（LPS）、腹腔注射 LPS 前 2 周口服 ZJ617s（ZJ617s+LPS）或腹腔注射 LPS 前 2 周口服 LGGs（LGGs+LPS）。测定全身炎症、肠道完整性、肝功能标志物、自噬和肝凋亡信号。
结果
LPS 注射后 24 小时，ZJ617s+LPS 组血清丙氨酸转氨酶和天冬氨酸转氨酶活性分别比 LPS 组低 32.2%和 30.3%（P<0.05）。ZJ617s+LPS 组比 LPS 组肠道闭合蛋白 3（claudin 3）（62.5%）、闭合蛋白（occludin）（60.1%）和封闭蛋白 1（zonula occludens 1）（60.5%）的表达更高（P<0.05）。ZJ617s+LPS 组肝组织白细胞介素-6 和肿瘤坏死因子-α的浓度分别比 LPS 组低 21.4%和 27.3%（P<0.05）。然而，ZJ617s+LPS 组白细胞介素-10 的浓度升高了 22.2%。LPS 组 Toll 样受体 4（TLR4）的表达增加了 50.5%，p38 丝裂原活化蛋白激酶（p38MAPK）的磷酸化增加了 57.1%，细胞外信号调节激酶（ERK）增加了 77.8%，c-Jun N-末端激酶（JNK）增加了 42.9%，核因子-κB（NF-κB）增加了 36.0%，与对照组相比。用 ZJ617s 或 LGGs 补充可改善这些作用（P<0.05）。此外，ZJ617s+LPS 组肝组织中活性半胱天冬酶-3 和微管相关蛋白 1 轻链 3 II 的表达分别比 LPS 组低 23.8%和 28.6%（P<0.05）。
结论
ZJ617s 通过抑制肝 TLR4/MAPK/NF-κB 激活、凋亡和自噬，对小鼠肝脏发挥有益作用。本试验在中国浙江大学（http://www.lac.zju.edu.cn）注册，编号为 ZJU20170529。
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