武汉大学人民医院麻醉科 湖北 武汉 430060
朴光宇,男,1999—,医学硕士生,主要从事肠缺血再灌注损伤与肠道菌群相互作用机制研究,E⁃mail:guangyupiao@163.com
孟庆涛,男,1976—,医学博士,教授,主要从事围术期脏器功能保护相关机制研究,E⁃mail:mengqingtao2018@126.com
收稿:2024-09-04,
纸质出版:2025-07-25
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朴光宇,施瑜,陈榕等.阿克曼嗜黏液菌外膜蛋白Amuc_1100调控STING信号通路减轻小鼠肠缺血再灌注损伤的机制[J].武汉大学学报(医学版),2025,46(07):836-841.
PIAO Guangyu,SHI Yu,CHEN Rong,et al.Mechanisms of outer membrane protein Amuc_1100 of Akkermansia muciniphila attenuating intestinal ischemia⁃reperfusion injury through STING signaling pathway in mice[J].Medical Journal of Wuhan University,2025,46(07):836-841.
朴光宇,施瑜,陈榕等.阿克曼嗜黏液菌外膜蛋白Amuc_1100调控STING信号通路减轻小鼠肠缺血再灌注损伤的机制[J].武汉大学学报(医学版),2025,46(07):836-841. DOI: 10.14188/j.1671-8852.2024.0674.
PIAO Guangyu,SHI Yu,CHEN Rong,et al.Mechanisms of outer membrane protein Amuc_1100 of Akkermansia muciniphila attenuating intestinal ischemia⁃reperfusion injury through STING signaling pathway in mice[J].Medical Journal of Wuhan University,2025,46(07):836-841. DOI: 10.14188/j.1671-8852.2024.0674.
目的
2
探讨阿克曼嗜黏液菌源性外膜蛋白Amuc_1100蛋白对小鼠肠缺血再灌注(IIR)损伤的影响。
方法
2
将18只健康雄性成年C57BL/6J小鼠随机分成3组:对照组(S组,
n
=6)、肠缺血再灌注组(IIR组,
n
=6)、肠缺血再灌注+Amuc_1100预处理组(IIR+Amuc_1100组,
n
=6)。对IIR+Amuc_1100组使用Amuc_1100蛋白(3 μg•d
-1
)预处理7 d,预处理完毕次日按分组制备小鼠肠缺血再灌注损伤模型,留取小肠组织。固定组织并按照标准HE染色程序染色,以观察组织改变,行Chiu's病理学损伤评分;检测小鼠肠组织超氧化物歧化酶(SOD)、丙二醛(MDA)表达水平;Western Blot法检测小鼠肠紧密连接蛋白表达以及干扰素基因刺激因子(STING)信号通路激活情况;酶联免疫吸附法检测小鼠血清中肿瘤坏死因子(TNF)⁃α、白细胞介素(IL)⁃6水平。
结果
2
与S组相比,IIR组Chiu's病理学损伤评分显著增高,SOD活性降低、MDA生成增加,紧密连接蛋白表达水平降低,而Amuc_1100蛋白预处理可显著降低肠缺血再灌注损伤所致Chiu's病理学损伤评分升高,增加SOD活性,并减少MDA生成,显著增加紧密连接蛋白表达水平。此外,与IIR组相比,Amuc_1100蛋白预处理显著降低IIR引起的p⁃STING、p⁃TBK1、p⁃NF⁃κB蛋白的过度表达,并显著降低IIR后的TNF⁃α、IL⁃6升高。
结论
2
Amuc_1100蛋白预处理能够减轻肠道肠缺血再灌注损伤,其机制可能是通过抑制STING信号通路异常激活。
Objective
2
To investigate the effects of Amuc_1100
an outer membrane protein derived from
Akkermansia muciniphila
on intestinal ischemia⁃reperfusion (IIR) injury in mice.
Methods
2
Eighteen healthy m
ale adult C57BL/6J mice were randomly divided into three groups: Control (S group
n
=6)
IIR (IIR group
n
=6)
and IIR+Amuc_1100 pretreatment (IIR+Amuc_1100 group
n
=6). Mice in the IIR+Amuc_1100 group were pretreated with Amuc_1100 protein (3 µg•d
-1
) for 7 days. On the following day
IIR injury models were established by occlusion of the superior mesenteric artery for 45 min followed by 2 h reperfusion
and small intestine tissues were collected. Tissues were fixed and stained using standard HE staining procedures to observe tissue changes and perform Chiu's pathological damage score. Superoxide dismutase (SOD) and malondialdehyde (MDA) levels in the intestinal tissues were measured. Western Blot was used to detect tight junction proteins expression and stimulator of interferons genes (STING) signaling pathway activation. ELISA was used to measure serum tumor necrosis factor (TNF)⁃α and interleukin (IL)⁃6 levels.
Results
2
Compared with the S group
the IIR group showed a significant increase in Chiu's score
decreased SOD activity
increased MDA production
and reduced tight junction protein expression. Amuc_1100 protein pretreatment significantly reduced the increase in Chiu's pathological damage score caused by IIR
increased SOD activity
decreased MDA production
and significantly increased tight junction protein expression. Additionally
Amuc_1100 pretreatment significantly reduced the IIR⁃induced overexpression of p⁃STING
p⁃TBK1
and p⁃NF⁃κB and decreased the elevated levels of TNF⁃α and IL⁃6 induced by IIR.
Conclusion
2
Amuc_1100 protein pretreatment alleviates intestinal ischemia⁃reperfusion injury
possibly through the inhibition of STING signaling pathway.
COLLARD C D , GELMAN S . Pathophysiology, clinical manifestations, and prevention of ischemia⁃reperfusion injury [J ] . Anesthesiology , 2001 , 94 ( 6 ): 1133 ⁃ 1138 .
CHEN J Y , WANG Y , SHI Y X , et al . Association of gut microbiota with intestinal ischemia/reperfusion injury [J ] . Front Cell Infect Microbiol , 2022 , 12 : 962782 .
WANG Y H , YAN Z Z , LUO S D , et al . Gut microbiota⁃derived succinate aggravates acute lung injury after intestinal ischaemia/reperfusion in mice [J ] . Eur Respir J , 2023 , 61 ( 2 ): 2200840 .
DAI D , DAI F D , CHEN J C , et al . Integrated multi⁃omics reveal important roles of gut contents in intestinal ischemia⁃reperfusion induced injuries in rats [J ] . Commun Biol , 2022 , 5 ( 1 ): 938 .
TANG J L , ZHAO M C , MIAO X , et al . Bifidobacterium longum GL001 alleviates rat intestinal ischemia⁃reperfusion injury by modulating gut microbiota composition and intestinal tissue metabolism [J ] . Food Funct , 2024 , 15 ( 7 ): 3653 ⁃ 3668 .
ZHAO M Q , TANG F , HUANG X Y , et al . Polysaccharide isolated from Agaricus blazei murill alleviates intestinal ischemia/reperfusion injury through regulating gut microbiota and mitigating inflammation in mice [J ] . J Agric Food Chem , 2024 , 72 ( 4 ): 2202 ⁃ 2213 .
DENG F , LIN Z B , SUN Q S , et al . The role of intestinal microbiota and its metabolites in intestinal and extraintestinal organ injury induced by intestinal ischemia reperfusion injury [J ] . Int J Biol Sci , 2022 , 18 ( 10 ): 3981 ⁃ 3992 .
HAN B , CHAO K , WANG D , et al . A purified membrane protein from Akkermansia muciniphila blunted the sepsis⁃induced acute lung injury by modulation of gut microbiota in rats [J ] . Int Immunopharmacol , 2023 , 121 : 110432 .
YANG Y C , WANG L , Peugnet⁃González I , et al . cGAS⁃STING signaling pathway in intestinal homeostasis and diseases [J ] . Front Immunol , 2023 , 14 : 1239142 .
DECOUT A , KATZ J D , VENKATRAMAN S , et al . The cGAS⁃STING pathway as a therapeutic target in inflammatory diseases [J ] . Nat Rev Immunol , 2021 , 21 ( 9 ): 548 ⁃ 569 .
HU X L , ZHANG H J , ZHANG Q X , et al . Emerging role of STING signalling in CNS injury: Inflammation, autophagy, necroptosis, ferroptosis and pyroptosis [J ] . J Neuroinflammation , 2022 , 19 ( 1 ): 242 .
PLOVIER H , EVERARD A , DRUART C , et al . A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice [J ] . Nat Med , 2017 , 23 ( 1 ): 107 ⁃ 113 .
CHEN S J , QIAN K Y , ZHANG G H , et al . Akkermansia muciniphila and its outer membrane protein Amuc_1100 prophylactically attenuate 5⁃fluorouracil⁃induced intestinal mucositis [J ] . Biochem Biophys Res Commun , 2022 , 614 : 34 ⁃ 40 .
孟庆涛 , 陈榕 , 刘慧敏 , 等 . Nrf2调控的炎症介质表达在肠缺血再灌注所致肾脏损伤中的作用 [J ] . 武汉大学学报(医学版) , 2017 , 38 ( 2 ): 189 ⁃ 192 .
MENG Q T , CHEN R , LIU H M , et al . Role of inflammatory mediators regulated by Nrf2 in intestinal ischemia⁃reperfusion induced kidney injury in rats [J ] . Med J Wuhan Univ , 2017 , 38 ( 2 ): 189 ⁃ 192 .
王宜衡 . 肠道菌群代谢物琥珀酸在肠缺血再灌注所致急性肺损伤的作用及机制研究 [D ] . 广州 : 南方医科大学 , 2023 .
WANG Y H . The role and mechanisms of gut microbiota metabolite succinate on acute lung injury induced by intestinal ischemia⁃reperfusion [D ] . Guangzhou : Southern Medical University , 2023 .
GU Z Y , PEI W L , SHEN Y H , et al . Akkermansia muciniphila and its outer protein Amuc_1100 regulates tryptophan metabolism in colitis [J ] . Food Funct , 2021 , 12 ( 20 ): 10184 ⁃ 10195 .
WANG L J , JIN Y L , PEI W L , et al . Amuc_1100 pretreatment alleviates acute pancreatitis in a mouse model through regulating gut microbiota and inhibiting inflammatory infiltration [J ] . Acta Pharmacol Sin , 2024 , 45 ( 3 ): 570 ⁃ 580 .
高薇薇 , 王枭 , 关鹏 . cGAS⁃STING信号通路与脓毒症肠屏障功能障碍相关性的研究进展 [J ] . 中国临床新医学 , 2023 , 16 ( 1 ): 102 ⁃ 106 .
GAO W W , WANG X , GUAN P . Research progress on the correlation between cGAS⁃STING signaling pathway and intestinal barrier dysfunction in sepsis [J ] . Chin J N Clin Med , 2023 , 16 ( 1 ): 102 ⁃ 106 .
WU J , LIU Q J , ZHANG X F , et al . STING⁃dependent induction of lipid peroxidation mediates intestinal ischemia⁃reperfusion injury [J ] . Free Radic Biol Med , 2021 , 163 : 135 ⁃ 140 .
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