伊索利基里通过Caspase 3/HMGB1/TLR4依赖信号通路改善了大鼠的性结肠炎
Zhiwei Miao1, Mingjia Gu2, Faisal Raza3
1Department of Gastroenterology, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, 215600, China.
Current gene therapy
|August 1, 2023
概括
性结肠炎 (UC) 模型中,flavanol glycoside 类型的伊索利基里有效降低了肠道炎症和粘膜损伤. 它通过抑制caspase-3/HMGB1/TLR4信号通路而起作用,为UC提供了潜在的治疗方法.
科学领域:
- 药理学 药理学是指药理学的学科.
- 胃肠病学 胃肠病学
- 分子生物学分子生物学
背景情况:
- 伊索利基瑞是一种因其强大的抗炎性质而闻名的醇糖化物.
- 性结肠炎 (UC) 是一种慢性炎症性肠病,具有显著的未满足治疗需求.
研究的目的:
- 在UC的临床前模型中研究异素的抗炎作用.
- 阐明潜在的分子机制,重点关注caspase-3/HMGB1/TLR4通路.
主要方法:
- 已建立的三二硫酸 (TNBS) 诱导的大肠炎模型在老鼠中.
- 在Caco-2细胞中利用脂聚糖 (LPS) 诱导的炎症模型.
- 分析了蛋白质和基因表达,使用西式涂抹,实时PCR,免疫组织化学和免疫光.
- 对UC相关蛋白质水平进行了生物信息分析.
主要成果:
- 伊索利基里治疗显著改善了结肠炎症状,包括缩短结肠长度,疾病活性指数 (DAI) 和体重减轻.
- 观察到炎症调解剂 (例如IL-1β,TNF-α) 和氧化应激标志物 (MDA,SOD) 的水平降低.
- 抑制了TLR4下游通路 (MyD88,IRAK1,TRAF6,NF-κB,p38,JNK) 的关键组成部分和上游配体HMGB1在mRNA和蛋白质水平上.
- 生物信息分析显示,肠炎中HMGB1,TLR4和caspase-3的高表达.
结论:
- 伊索利奎里丁在体内和体外表现出显著的抗结肠炎和抗炎作用.
- 异基的治疗作用通过抑制caspase-3/HMGB1/TLR4信号通路进行介导.
- 伊索利基里为治疗性结肠炎提供了一个有前途的治疗候选药物.
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