[1]黄利民,徐源佑,王璐璐,等.IL-6/STAT3信号通路在脓毒症所致骨骼肌消耗中的作用机制研究[J].肠外与肠内营养杂志,2023,(06):368-374.[doi:DOI : 10.16151/j.1007-810x.2023.06.009]
　HUANG Li-min,XU Yuan-you,WANG Lu-lu,et al.Mechanism of IL-6/STAT3 signaling pathway in sepsis induced skeletal muscle wasting[J].PARENTERAL & ENTERAL NUTRITION,2023,(06):368-374.[doi:DOI : 10.16151/j.1007-810x.2023.06.009]
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IL-6/STAT3信号通路在脓毒症所致骨骼肌消耗中的作用机制研究()
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《肠外与肠内营养》杂志[ISSN:1007-810X/CN:32-1477/R]

卷:
期数:
2023年06期
页码:
368-374
栏目:
论著
出版日期:
2023-12-10

文章信息/Info

Title:
Mechanism of IL-6/STAT3 signaling pathway in sepsis induced skeletal muscle wasting
作者:
黄利民1; 徐源佑 2; 王璐璐2; 陈鑫玥 2; 段 婷 2; 陆国玉 1; 2
1.蚌埠医学院第一附属医院急诊外科，安徽蚌埠 233000；2.南京大学医学院附属金陵医院/东部战区总医院急诊医学科，江苏南京 210002
Author(s):
HUANG Li-min1;  XU Yuan-you2;  WANG Lu-lu2;  CHEN Xin-yue2;  DUAN Ting2;  LU Guo-yu1; 2
1.Department of Emergency Surgery, the First Affiliated Hospital of Bengbu Medical College, Bengbu233000, Anhui, China；2. Department of Emergency Medicine, Jinling Hospital, Medical School ofNanjing University, Nanjing 210002, Jiangsu, China
关键词:
脓毒症 ; 骨骼肌消耗 ; 白介素-6 ; 炎症因子
Keywords:
Sepsis;  Skeletal muscle wasting;  Interleukin-6;  Inflammatory cytokine
分类号:
R459.7
DOI:
DOI : 10.16151/j.1007-810x.2023.06.009
文献标志码:
A
摘要:
目的：探索 IL-6/STAT3信号通路在腹腔脓毒症所导致的骨骼肌消耗中的具体作用及机制。 方法：10周龄 SPF级 C57BL/6健康雄性小鼠随机分为对照组（假手术组）和盲肠结扎穿孔制备腹腔脓毒症组后，在脓毒症组内随机分为对照脓毒症组、脓毒症+抗 IL-6单抗组以及脓毒症+酪氨酸激酶抑制剂 AG490组，以观察阻断 IL-6信号通路对脓毒症小鼠骨骼肌消耗的影响。实验周期为 72 h，抗 IL-6单抗组及 AG490的给药方式均为腹腔注射，每24小时给药一次。实验结束后留取小鼠的双侧后肢背侧腓肠肌，称重后制作骨骼肌冰冻切片。免疫荧光染色检测小鼠骨骼肌层粘连蛋白（Laminin蛋白），并检测小鼠骨骼肌纤维横截面积。q-PCR以及 Western Blot 方法检测小鼠骨骼肌萎缩和炎症相关蛋白表达。 结果：与对照组（假手术组）相比，脓毒症小鼠的 IL-6信号通路显著激活，表现为建模后 24 h、48 h 以及 72 h 的 IL-6 水平及 p-STAT3/STAT3 比值显著升高（P < 0.05），而骨骼肌肌球蛋白重链（MYHC）含量显著下降（P < 0.05）。通过腹腔注射抗 IL-6单抗组或者 AG490阻断 IL-6/STAT3信号通路，可显著的增加小鼠的体质量及腓肠肌重量（P < 0.05），且增加小鼠的骨骼肌平均肌纤维面积及骨骼肌平均纤维直径（P <0.01），并显著的降低骨骼肌组织中萎缩相关基因 Murf-1（P < 0.05）和 Atrogin-1（P < 0.05）的表达。同时，小鼠的骨骼肌 MYHC蛋白表达量均显著增加（P < 0.01）。 结论：脓毒症状态下，IL-6升高导致的 IL-6/STAT3 信号通路激活是导致骨骼肌组织萎缩的重要原因之一。通过增加 IL-6的清除，或者阻断 IL-6的细胞内信号传导途径，可有效的改善脓毒症小鼠的骨骼肌消耗情况。
Abstract:
Objective: To explore the specific role and mechanism of IL-6/STAT3 signaling pathway in skeletalmuscle wasting caused by abdominal sepsis. Method: SPF C57BL/6 healthy 10-week-old male mice were randomlydivided into control group (sham operation group) and abdominal sepsis group (by cecum ligation and puncture). Afterthat, sepsis group was randomly divided into control sepsis group, sepsis + anti-IL-6 monoclonal antibody group andsepsis + tyrosine kinase inhibitor AG490 group. The experimental period was 72 hours. The anti-IL-6 monoclonalantibody group and AG490 were administered by intraperitoneal injection every 24 hours. The mice were euthanized andboth gastrocnemius muscles were removed 24 hours after the last injection. The laminin distribution in the muscles wasassessed following immunofluorescence staining, and the cross-sectional area were assessed. q-PCR and Western Blot was used to measure the expression of proteins related to atrophy and inflammation in skeletal muscle. Results:Compared with the control group (sham operation group), the IL-6 signaling pathway was significantly activated insepsis mice, as IL-6 levels and p-STAT3/STAT3 ratio were significantly increased at 24, 48, and 72 hours after CLPperforming (P < 0.05), while MYHC content was significantly decreased (P < 0.05). IL-6/STAT3 signaling pathwayblocking by injection of anti-IL-6 monoclonal antibody or AG490 could significantly increase body weight andgastrocnemius muscle weight (P < 0.05), and also increase the mean muscle fiber areas and mean muscle fiber diameterscompared with those in the sepsis group (P < 0.01). In addition, the atrophy-related gene expression of Murf-1 andAtrogin-1 in the IL-6 blocking group was significantly lower than that in the sepsis group (P < 0.05), while the proteinexpression of MYHC in skeletal muscle was significantly increased (P < 0.01). Conclusion: In sepsis, activation of IL-6/STAT3 signaling pathway caused by IL-6 elevation plays a pivotal role in skeletal muscle atrophy. Increasing theclearance or blocking the intracellular signaling pathway of IL-6 could effectively alleviate the skeletal muscle atrophyfor sepsis mice.

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备注/Memo

备注/Memo:
基金项目 ：安徽省教育厅科学研究项目（伦科批字[2022]第 191号）作者简介 ：黄利民，主治医师，医学硕士，从事急诊医学工作。E-mail：18351875182@163.com通讯作者 ：陆国玉，E-mail：1359112431@qq.com
更新日期/Last Update: 1900-01-01