STING通过调解自和巨两极分化来调节与HBV相关的急性至慢性肝衰竭
Hao Zhang1, Teng Liang1, Wanlu Duan1
1Department of Clinical Laboratory, Second Affiliated Hospital of Anhui Medical University, No. 678, Furong Road, Hefei 230601, Anhui, China.
Immunobiology
|December 20, 2024
概括
在HBV-ACLF小鼠模型中,STING激活最初通过上调自性来保护肝损伤. 然而,稍后的STING激活会通过促进M1巨细胞的两极分化和炎症而加剧肝损伤.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 与乙型肝炎病毒相关的急性至慢性肝衰竭 (HBV-ACLF) 的死亡率很高.
- 现有的实验模型不能充分代表由慢性乙型肝炎 (CHB) 引起的HBV-ACLF.
- 需要一个可靠的实验模型来研究HBV-ACLF和治疗点.
研究的目的:
- 建立基于CHB的HBV-ACLF的新型小鼠模型.
- 研究在HBV-ACLF中STING (干扰素基因刺激器) 路径激活的作用.
- 探索调节STING活动的治疗潜力.
主要方法:
- 通过诱导慢性HBV复制和急性肝损伤,使用pAAV/HBV1.2等离子体和乙氨基 (APAP) 开发了一种小鼠模型.
- 对模型小鼠施用了STING激动剂或抑制剂.
- 评估肝损伤,STING通路激活,自流和巨分化.
主要成果:
- 建立的模型部分回顾了基于CHB的HBV-ACLF的临床特征.
- 用激动剂早期激活STING (6小时) 缓解了肝损伤,增加了自,并激活了STING通路.
- 晚期STING激活 (24-48小时) 用激动剂导致M1巨细胞两极分化,炎症增加,肝损伤恶化.
- 用STING抑制剂治疗逆转了后期阶段观察到的有害影响.
结论:
- 刺痛诱导的自提供了早期保护,防止HBV-ACLF肝损伤.
- 晚期的STING激活可以通过促进M1巨细胞两极分化和增强炎症来恶化HBV-ACLF.
- 向STING调制可能为HBV-ACLF提供治疗策略,时机至关重要.
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