华中科技大学学报(医学版) ›› 2026, Vol. 55 ›› Issue (3): 340-345.doi: 10.3870/j.issn.1672-0741.25.09.021

• 论著 • 上一篇    下一篇

circRNA-007371通过调控CX3CR1介导肝星状细胞焦亡在肝纤维化中的作用机制*

黄莎莎, 韩峥, 卢圆媛, 王逸云, 田霞   

  1. 武汉大学附属同仁医院(武汉市第三医院)消化内科,武汉 430060
  • 收稿日期:2025-09-16 出版日期:2026-06-15 发布日期:2026-06-17
  • 通讯作者: E-mail:18053911757@163.com
  • 作者简介:黄莎莎,女,1987年生,医学硕士,E-mail:18622172533@163.com
  • 基金资助:
    *湖北省自然科学基金指导性计划项目(No.2024AFC064)

circRNA-007371 Regulates CX3CR1 to Mediate Hepatic Stellate Cell Pyroptosis in Liver Fibrosis

Huang Shasha, Han Zheng, Lu Yuanyuan et al   

  1. Department of Gastroenterology, Wuhan University Affiliated Tongren Hospital(Wuhan Third Hospital), Wuhan 430060, China
  • Received:2025-09-16 Online:2026-06-15 Published:2026-06-17
  • Contact: E-mail:18053911757@163.com

摘要: 目的 探究circRNA-007371调控CX3CR1介导肝星状细胞(HSC)焦亡在肝纤维化(LF)中的作用及可能机制。方法 将30只大鼠分为对照(CON)组、LF组与低表达circRNA-007371(L-circRNA-007371)组,每组10只。培养HSC-T6细胞,分为CON组、过表达circRNA-007371(H-circRNA-007371)组与NLRP3抑制(Antcin A)组。Sirius Red染色检测肝组织纤维化水平。免疫荧光染色检测肝组织α-SMA、Collagen1蛋白水平。qRT-PCR实验检测肝组织与HSC-T6中circRNA-007371、CX3CR1、α-SMA、Collagen1 mRNA水平。HE染色检测肝组织病理变化。Masson染色检测肝组织胶原沉积情况。Western blot检测肝组织与HSC-T6细胞中NLRP3、Caspase-1及GSDMD蛋白水平。ELISA试剂盒检测血清与HSC-T6中IL-1β、IL-18含量。结果 与CON组比较,LF组大鼠肝组织胶原纤维增生,纤维化相关蛋白α-SMA、Collagen1表达增加,circRNA-007371与CX3CR1 mRNA水平增加(均P<0.05),肝组织出现病理损伤,伴有肝脂肪变性和脂肪空泡,肝小叶结构异常,胶原蛋白明显增加,肝组织焦亡相关蛋白NLRP3、Caspase-1及GSDMD蛋白水平增加(均P<0.05),血清IL-1β、IL-18含量增加(均P<0.05);与LF组比较,L-circRNA-007371组肝组织circRNA-007371与CX3CR1 mRNA水平降低(均P<0.05),肝组织病理损伤改善,胶原蛋白减少,肝组织中NLRP3、Caspase-1及GSDMD蛋白水平降低(均P<0.05),血清中IL-1β、IL-18含量减少(均P<0.05)。与CON组比较,H-circRNA-007371组HSC-T6细胞中circRNA-007371、CX3CR1、α-SMA、Collagen1 mRNA水平增加(均P<0.05),NLRP3、Caspase-1及GSDMD蛋白水平增加(均P<0.05),IL-1β、IL-18含量增加(均P<0.05);与H-circRNA-007371组比较,Antcin A组HSC中circRNA-007371、CX3CR1、α-SMA、Collagen1 mRNA水平降低(均P<0.05),NLRP3、Caspase-1及GSDMD蛋白水平降低(均P<0.05),IL-1β、IL-18含量减少(P<0.05)。结论 低表达circRNA-007371可通过调控CX3CR1抑制HSC焦亡改善LF。

关键词: 肝纤维化, 肝星状细胞, circRNA-007371, CX3CR1, 焦亡

Abstract: Objective To investigate the role of circRNA-007371 in regulating CX3CR1-mediated hepatic stellate cell(HSC)pyroptosis in liver fibrosis(LF)and its possible mechanism. Methods Thirty rats were divided into control group,LF group and low expression circRNA-007371 group,with 10 rats in each group.HSC-T6 cells were cultured and divided into control group,circRNA-007371 overexpression group and NLRP3 inhibition(Antcin A)group.The level of LF was detected by Sirius Red staining.The levels of α-SMA and Collagen1 proteins in liver tissue were detected by immunofluorescence staining.The mRNA levels of circRNA-007371,CX3CR1,α-SMA and Collagen1 in liver tissue and HSC-T6 were detected by qRT-PCR.HE staining was used to detect the pathological changes of liver tissue.Masson staining was used to detect collagen deposition in liver tissue.Western blotting was used to detect NLRP3,Caspase-1 and GSDMD protein levels in liver tissue and HSC-T6.The IL-1β and IL-18 levels in serum and HSC-T6 were detected by ELISA. Results Compared with the control group,the liver tissue of LF group showed hyperplasia of collagen fiber,the protein expression levels of α-SMA and Collagen1,the mRNA expression levels of circRNA-007371 and CX3CR1 were increased(P<0.05),the liver tissue showed pathological injury,accompanied by liver steatosis and fat cavity;hepatic lobular structure was abnormal,collagen was increased significantly,the levels of NLRP3,Caspase-1 and GSDMD proteins in liver tissue were increased(P<0.05),and the serum IL-1β and IL-18 levels were increased(P<0.05).Compared with LF group,mRNA expression levels of circRNA-007371 and CX3CR1 in liver tissues of low-expression circRNA-007371 group were decreased(P<0.05),liver tissue pathological injury was alleviated,and collagen protein was reduced;the levels of NLRP3,Caspase-1 and GSDMD proteins in liver tissue were decreased(P<0.05),and the serum IL-1β and IL-18 levels were decreased(P<0.05).Compared with the control group,the mRNA expression levels of circRNA-007371,CX3CR1,α-SMA and Collagen1 in HSC in over-expression group were increased(P<0.05),the protein expression levels of NLRP3,Caspase-1 and GSDMD were increased(P<0.05),and the IL-1β and IL-18 levels were increased(P<0.05).Compared with the over-expression circRNA-007371 group,the mRNA expression levels of circRNA-007371,CX3CR1,α-SMA and Collagen1 in the HSC of Antcin A group were decreased(P<0.05),the protein expression levels of NLRP3,Caspase-1 and GSDMD were decreased(P<0.05),and the contents of IL-1β and IL-18 were decreased(P<0.05). Conclusion Low expression of circRNA-007371 can alleviate LF by inhibiting pyroptosis of HSC by regulating CX3CR1.

Key words: liver fibrosis, hepatic stellate cells, circRNA-007371, CX3CR1, pyroptosis

中图分类号: