炎调方通过Fas/Caspase-8信号通路减轻脓毒症急性胃肠损伤小鼠炎症的机制研究  

Exploring the mechanism of Yantiao Fang in reducing inflammation in mice with sepsis-induced acute gastrointestinal injury through the Fas/Caspase-8 signaling pathway

作　　者：王帝[1] 陈乾 邓健超 王萌 王丽辉 李燕红[3] 李华 WANG Di;CHEN Qian;DENG Jian-chao;WANG Meng;WANG Li-hui;LI Yan-hong;LI Hua(Second Clinical Medical College,Henan University of Chinese Medicine,Zhengzhou 450000,China;Second Affiliated Hospital of Henan University of Chinese Medicine,Henan Provincial Hospital of Traditional Chinese Medicine,Zhengzhou 450000,China;Huanghe Science and Technology College,Zhengzhou 450000,China)

机构地区：[1]河南中医药大学第二临床医学院,河南郑州450000 [2]河南省中医院,河南中医药大学第二附属医院,河南郑州450000 [3]黄河科技学院,河南郑州450000

出　　处：《时珍国医国药》2025年第2期209-214,共6页Lishizhen Medicine and Materia Medica Research

基　　金：国家自然科学基金青年基金(82104833);河南省科技厅科技攻关项目(242102311259);河南省高等学校重点科研项目计划(21A320009);河南省中医药学科领军人才培养项目(豫卫中医函[2021]8号);河南省中医药科学研究专项课题(2024ZY2063,2024ZYZD05,2024ZY2084)。

摘　　要：目的探讨炎调方调过Fas/Caspase-8信号通路减轻脓毒症急性胃肠损伤小鼠炎症的机制。方法取70只BALB/c小鼠随机分为空白组、假手术组和造模小鼠组。通过盲肠结扎穿孔术(cecum ligation and puncture,CLP)构建脓毒症急性胃肠损伤小鼠模型,将造模成功的小鼠随机分为模型组,炎调方低、中、高剂量组,ROCK抑制剂组。苏木素-伊红(HE)染色观察小鼠回肠组织病理学改变;ELISA法检测各组小鼠血清IL-17、IL-23水平;蛋白印迹法检测回肠组织Fas/Caspase-8信号通路蛋白Fas、FADD和Caspase-8的相对表达;TUNEL染色法检测回肠组织细胞凋亡情况。结果与空白组相比,模型组小鼠回肠组织肠黏膜萎缩明显、绒毛排列杂乱,可见断裂、脱落,上皮细胞细胞坏死脱落,炎症细胞浸润明显,小鼠血清中IL-17、IL-23水平升高(P<0.05),回肠组织中Fas、FADD和Caspase-8蛋白的表达升高(P<0.05),肠上皮细胞呈现明显的凋亡现象(P<0.05)。与模型组相比,炎调方组小鼠的回肠组织病理学改变均得到不同程度的改善,血清中IL-17、IL-23水平降低(P<0.05),且回肠组织中Fas、FADD和Caspase-8蛋白的表达降低(P<0.05),肠上皮细胞凋亡减少(P<0.05)。结论炎调方可以减轻肠黏膜组织损伤和肠道组织炎症反应,可能是通过调控Fas/Caspase-8信号通路抑制脓毒症急性胃肠损伤小鼠的肠上皮细胞凋亡来发挥作用的。Objective To investigate the mechanism of Yantiao Fang(YTF)in reducing inflammation in mice with sepsis-induced acute gastrointestinal injury(SAGI)through regulating Fas/Caspase-8 signaling pathway.Methods Seventy BALB/c mice were randomly divided into the normal group,the sham group and the model group.A mouse model of SAGI was constructed by cecal ligation and puncture(CLP).The successfully modeled mice were randomly divided into the model,YTF Low-dose(YTF-L),Medium-dose(YTF-M)and High-dose(YTF-H)groups,and the ROCK inhibitor group.Hematoxylin-eosin(HE)staining was used to observe the pathological changes of ileum tissue in mice.The levels of serum IL-17 and IL-23 in each group were detected by ELISA.Western blot(WB)was used to detect the relative expression of Fas,FADD and Caspase-8 in ileum tissue.TUNEL staining was used to detect the apoptosis of ileal cells.Results Compared with the normal group,the intestinal mucosa of the ileum tissue of the mice in the model group was significantly atrophied,the villi were arranged in disorder,visible breakage and shedding,epithelial cell necrosis and shedding,inflammatory cell infiltration were obvious,and the levels of IL-17 and IL-23 in the serum of the mice were increased(P<0.05).The expression of Fas,FADD and Caspase-8 protein in ileum tissue was increased(P<0.05).Intestinal epithelial cells showed obvious apoptosis(P<0.05).Compared with the model group,the pathological changes of ileum tissue in the YTF group were alleviated to varying degrees.The levels of IL-17 and IL-23 in serum were decreased(P<0.05).The expression of Fas,FADD and Caspase-8 protein in ileum tissue was decreased(P<0.05).The apoptosis of intestinal epithelial cells was decreased(P<0.05).Conclusion YTF can reduce intestinal mucosal tissue injury and intestinal tissue inflammation,which may play a role in inhibiting intestinal epithelial cell apoptosis in mice with SAGI by regulating the Fas/Caspase-8 signaling pathway.

关 键 词：炎调方 脓毒症急性胃肠损伤 Fas/Caspase-8信号通路 细胞凋亡 

分 类 号：R285.5[医药卫生—中药学]