大黄素、黄芩素联用通过抑制PLC/IP3/Ca2+通路缓解腺泡细胞损伤治疗大鼠重症急性胰腺炎的实验研究
结题报告
批准号:
81973659
项目类别:
面上项目
资助金额:
55.0 万元
负责人:
李君
依托单位:
学科分类:
中西医结合临床基础
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
李君
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中文摘要
腺泡细胞钙超载致细胞损伤是重症急性胰腺炎(SAP)发生的重要机制之一。课题组前期研究发现,大黄素黄芩素联用可通过多环节有效治疗SAP,降低IP3R的mRNA及蛋白质水平的表达,降低Ca2+浓度,减轻钙超载及腺泡细胞损伤。腺泡细胞内Ca2+稳态调节受PLC/IP3/Ca2+信号通路调控,由此推测大黄素黄芩素联合治疗SAP的机制是作用于腺泡细胞PLC/IP3/Ca2+信号通路。本研究拟建立体外细胞系统和体内SAP动物模型,以PLC/IP3/Ca2+通路为切入点,研究大黄素黄芩素联用对腺泡细胞损伤的缓解作用及机制。具体分析大黄素黄芩素作用下该通路相关蛋白质表达和磷酸化水平,比较通路激动剂、阻断剂的效应,分析效应分子中炎症因子和酶活性。目标是阐明腺泡细胞PLC/IP3/Ca2+信号通路在SAP大黄素黄芩素联用治疗中的作用及机制,为深入理解SAP发病机制、揭示大黄素黄芩素联用效果和机制提供实验依据。
英文摘要
The calcium overload in pancreatic acinar cells plays a central role in the pathogenesis of severe acute pancreatitis(SAP).The previous experimental results of us showed a good effect of the synergy between Emodin and Baicalein on SAP and the mechanisms were confirmed by decreasing the expression of inositol triphosphate receptor(IP3R) ,decreasing the intracellular free calcium concentration and protecting cell injury in isolated rat pancreatic acinar cells. Current findings have proved that the PLC/IP3/Ca2+ signal pathway is crucial in regulating of Ca2+ signals in cells and we suggest a new hypothesis that the mechanisms of combine application of Emodin and Baicalein were relevant to the PLC/IP3/Ca2+ signal pathway. In this project, we will establish an in vitro cell system and an in vivo SAP animal model to investigate the amelioration of the synergy between Emodin and Baicalein on cell damage starting from PLC/IP3/Ca2+ pathway. We will examine the protein expression and phosphorylation level of PLC/IP3/Ca2+ signal pathway, compare the effects of pathway agonists and antagonist and analyze inflammatory factors and enzyme activities under the action of synergy between Emodin and Baicalein. The aim is to illuminate the role and mechanism of PLC/IP3/Ca2+ signal pathway in the process of synergy between Emodin and Baicalein on SAP. This will provide beneficial evidence for explicating the pathogenesis of SAP and the mechanism of synergy between Emodin and Baicalein.
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DOI:10.3390/medicina59020321
发表时间:2023-02-09
期刊:Medicina (Kaunas, Lithuania)
影响因子:--
作者:
通讯作者:
DOI:--
发表时间:2021
期刊:中华实验外科杂志
影响因子:--
作者:周蕊;黄娜;张健;陈海燕;张少颖;杨军;李君(通讯作者);李宗芳
通讯作者:李宗芳
DOI:--
发表时间:2021
期刊:西部医学
影响因子:--
作者:周蕊;张健;黄娜;陈海燕;谭婷;朱建宏;张爱军;杨军;李君(通讯作者);李宗芳
通讯作者:李宗芳
大黄素、黄芩素联合应用对重症急性胰腺炎大鼠脾脏炎症因子分泌及胰腺腺泡细胞钙超载的干预作用及其机制研究
  • 批准号:
    30901945
  • 项目类别:
    青年科学基金项目
  • 资助金额:
    20.0万元
  • 批准年份:
    2009
  • 负责人:
    李君
  • 依托单位:
国内基金
海外基金