海南医科大学学报2025，Vol.31Issue(14)：1069-1076,8.DOI:10.13210/j.cnki.jhmu.20240914.002
柴胡皂苷D调节cGAS-STING信号通路改善重症急性胰腺炎大鼠肠损伤
Saikosaponin D modulates cGAS-STING signaling pathway to improve intestinal injury in rats with severe acute pancreatitis
摘要
Abstract
Objective:To investigate the impacts of saikosaponin D(SSD)on intestinal injury in rats with severe acute pancre-atitis(SAP)by regulating the cyclic GMP-AMP synthase(cGAS)-stimulator of interferon gene(STING)signaling pathway.Methods:SAP rat model was established.And randomly divided into the model group,the SSD low dose group(12.5 mg/kg),the SSD medium dose group(25 mg/kg),the SSD high dose group(50 mg/kg),the positive drug group(2×104 U/kg ulinastatin),and the SSD high dose+cGAS overexpression group(50 mg/kg SSD+100 μL cGAS recombinant plasmid pcDNA3.1 vector),with 12 mice per group.Another 12 rats were selected as the sham operation group.Each group was given corresponding drug in-tervention for 7 days,once a day.The levels of serum lipase and amylase were detected by automatic biochemical analyzer;ileal tissue interleukin(IL)-6,IL-1β and tumor necrosis factor-α(TNF-α)levels were detected by enzyme-linked immunosorbent as-say;the pathological changes of pancreatic and ileal tissue were detected by hematoxylin-eosin staining;TUNEL staining was used to detect apoptosis in ileal tissue;Western blot detected the expression of Occludin,zonula occludens-1(ZO-1),cGAS and STING in ileal tissue.Results:Compared with the sham operation group,the serum lipase,amylase,ileal tissue IL-6,IL-1β,TNF-α,pathological scores of pancreas and ileal tissue,apoptosis rate of cells in ileal tissue,cGAS and STING protein expres-sion in the model group were significantly increased,and the expressions of Occludin and ZO-1 protein were significantly decreased(P<0.05).Compared with model group,the serum lipase,amylase,ileal tissue IL-6,IL-1β,TNF-α,pathological scores of pan-creas and ileal tissue,apoptosis rate of cells in ileal tissue,and cGAS and STING protein expression in ileal tissue of rats in SSD low,medium,high dose groups were decreased in a dose-dependent manner,and the expression of Occludin and ZO-1 protein were increased in a dose-dependent manner(P<0.05).Overexpression of cGAS can reduce the effect of high dose SSD on the above indexes in SAP rats(P<0.05).Conclusion:SSD may inhibit cGAS-STING signaling pathway,reduce ileal tissue inflam-matory response and cell apoptosis,and improve intestinal injury in SAP rats.关键词
柴胡皂苷D/重症急性胰腺炎/环磷酸鸟苷-腺苷酸合成酶/干扰素基因刺激因子/肠损伤Key words
Saikosaponin D/Severe acute pancreatitis/Cyclic GMP-AMP synthase/Stimulator of interferon gene/Intesti-nal injury分类
医药卫生引用本文复制引用
陈铮月,邓晚秋,尹建军,刘微,温建立..柴胡皂苷D调节cGAS-STING信号通路改善重症急性胰腺炎大鼠肠损伤[J].海南医科大学学报,2025,31(14):1069-1076,8.基金项目
This study was supported by the Science and Technology Fund Project of Guizhou Provincial Health Commission(gzwjkj2022-1-224) 贵州省卫生健康委科学技术基金项目(gzwjkj2022-1-224) （gzwjkj2022-1-224）
