课题基金基金详情
锦红汤调控TGR5/Ras/MAPK3改善急性胆管炎胆管上皮屏障损伤的机制研究
结题报告
批准号:
82004372
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
余奎
依托单位:
学科分类:
中医外科学
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
余奎
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中文摘要
急性胆管炎(AC)是外科常见的危急重症,死亡率较高,胆管上皮屏障的完整性在AC的治疗及预后中发挥着重要的作用。胆汁酸受体TGR5是调控胆管上皮细胞增生、维持胆管上皮紧密连接的关键,已成为治疗AC的潜在靶点。锦红汤是海派中医顾氏外科名方,应用于外科急腹症治疗已40余年,临床疗效确切。本课题组前期研究表明,锦红汤可减轻AC患者炎症反应、逆转肝细胞损伤、促进胆管上皮细胞修复;锦红汤还可激活炎症状态下胆管上皮细胞TGR5并抑制MAPK3的表达,提示其可能通过调控TGR5、MAPK3来发挥保护胆管上皮屏障的作用,但具体调控机制仍不明确。本研究拟先使用AC动物模型,验证锦红汤对炎症的改善作用;其次,采用炎症细胞模型,通过分别阻断TGR5及MAPK3的表达,探讨锦红汤调控TGR5/Ras/MAPK3信号通路的作用机制,明确锦红汤促进胆管上皮细胞增生及保护上皮屏障的作用,为锦红汤治疗AC提供现代科学依据。
英文摘要
Acute cholangitis (AC) is a common critical disease in surgery with high mortality. The integrity of bile duct epithelial barrier plays an important role in the treatment and prognosis of AC. Bile acid receptor TGR5 is the key to regulate bile duct epithelial cell proliferation and maintain bile duct epithelial tight junction, and has become a potential target for the treatment of AC. Jinhong decoction is a famous prescription of Shanghai Traditional Chinese Medicine Gu's surgery, which has been used in the treatment of surgical acute abdomen for more than 40 years, and the clinical effect is definite. Previous studies of our group have shown that Jinhong decoction can reduce inflammatory reaction, reverse hepatocyte injury and promote bile duct epithelial cell repair in patients with AC. Jinhong decoction can also activate TGR5 and inhibit the expression of MAPK3 in bile duct epithelial cells under inflammatory state, suggesting that Jinhong decoction may play a role in protecting bile duct epithelial barrier by regulating TGR5 and MAPK3, but the specific regulation mechanism is still unclear. This study intends to use AC animal model to verify the improvement effect of Jinhong decoction on inflammation; secondly, using inflammatory cell model, by blocking the expression of TGR5 and MAPK3 respectively, to explore the mechanism of Jinhong decoction regulating TGR5/Ras/MAPK3 signal pathway, to clarify the role of Jinhong decoction in promoting bile duct epithelial cell proliferation and protecting epithelial barrier, so as to provide modern scientific basis for Jinhong decoction in the treatment of AC.
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DOI:https://kns.cnki.net/kcms/detail//21.1128.R.20230213.1111.071.html
发表时间:2023
期刊:辽宁中医杂志
影响因子:--
作者:梅丹;王伟;周伟科;葛晓军;李廷;余奎;杨吉勇;叶圳;顾宏刚;张静喆
通讯作者:张静喆
DOI:--
发表时间:2023
期刊:中国比较医学杂志
影响因子:--
作者:余奎;梁晓强;韩冕;张静喆
通讯作者:张静喆
国内基金
海外基金