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滋阴清热复方降低ROS/MT-CO1异常与中西医协同治疗SLE互补新机制

批准号:
82074172
项目类别:
面上项目
资助金额:
55.0 万元
负责人:
程喜平
依托单位:
学科分类:
中西医结合临床基础
结题年份:
2024
批准年份:
2020
项目状态:
已结题
项目参与者:
程喜平

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中文摘要
研究中西医协同治疗SLE互补机制意义重大。我们证实滋阴清热复方降ROS、GC升ROS;线粒体MT-CO1对ROS损害易感并在狼疮鼠异常下降。ROS为重要促炎分子,ROS与MT-CO1恶性循环可促进炎症。我们推测GC线粒体途径蓄积性加重ROS/MT-CO1恶性循环的促炎作用达阈值后,突破GC细胞核途径抗炎效应的屏蔽,致狼疮活动不定期复发,是GC副作用机理之一;中西药对ROS相反作用是中西医互补机制之一。课题为研究中西医协同治疗SLE互补新机制,首次将ROS/MT-CO1引进SLE领域,线粒体、细胞水平分别干预ROS,从细胞器到整体多层级研究ROS/MT-CO1在SLE中作用,多时段重点研究GC线粒体途径蓄积性加重ROS/MT-CO1异常与狼疮活动复发的关系;中药和GC多组合干预,明确中西医相反调控ROS/MT-CO1对狼疮活动影响;锁定中西医协同治疗SLE互补新机制及GC促炎副作用机理研究。
英文摘要
It is of great significance to study the complementary mechanism of Traditional Chinese Medicine (TCM) and Western Medicine synergistic treatment for SLE. ROS is an important pro-inflammatory molecule. We confirmed that Nourishing Yin Clearing Heat formula can reduce ROS while glucocorticoid (GC) can increase ROS. Mitochondrial cytochrome c oxidase subunit 1 (MT-CO1) was susceptible to ROS damage and decreased abnormally in lupus mice, suggesting a vicious cycle can exist between MT-CO1 and ROS which may promote inflammation. We speculate that GC mitochondrial pathway break through the anti-inflammatory shield of GC nuclear pathway, which can cumulatively aggravate the ROS / MT-CO1 vicious cycle, leading to the irregular recurrence of lupus activity, which is one of the side effects of GC. The reverse regulatory effect of Chinese and Western Medicine on ROS is one of the complementary mechanism of TCM and Western medicine. In order to study the new complementary mechanism of combined Chinese and western medicine treatment of SLE, we first time introduces mitochondrial ROS/MT-CO1 into the field of SLE. We will intervene ROS at the mitochondrial and cellular levels, and the role of ROS/MT-CO1 in SLE was studied from organelle to the whole multilayer level. The periodic observation was used to investigate the relationship between GC accumulation promoting ROS/MT-CO1 abnormalities and lupus activity recurrence. The multi-combination intervention of TCM and GC was used to clarify the effect of ROS/MT-CO1 on lupus activity by the opposite regulation of TCM and western medicine. We Targeted study on the new complementary mechanism of combined Chinese and western medicine treatment of SLE and the mechanism of side effects of GC in promoting inflammation.
本课题主要探讨了GC是否通过线粒体途径加剧这些异常,突破GC的核途径抗炎作用,从而导致狼疮活动不定期复发。同时,研究了滋阴清热复方是否能够改善这些异常,减少GC治疗期间狼疮活动的复发。在研究中,我们团队发现地塞米松能够促进GR向线粒体内转运,并与线粒体基因GRE位点结合,负调控线粒体呼吸链复合体Ⅳ基因的表达。GC通过线粒体途径的调控可导致线粒体功能异常,进而加剧氧化应激损害。此外,GC还通过调控线粒体通透性增加,诱发mtDNA和细胞色素C外泄,从而引发细胞凋亡和焦亡。滋阴清热复方能够减轻GC引起的线粒体功能异常、氧化应激损害以及细胞焦亡和凋亡,从而减轻GC在线粒体调控中的致病作用。滋阴清热复方中的中药成分,如地黄苷和丹皮酚,能够进入线粒体。使用TSPO特异性抑制剂pk11195时,发现地黄苷和丹皮酚的线粒体跨膜转运量明显减少,首次表明TSPO在中药单体的线粒体转运中起着关键作用。另外,GC与PD-L1小分子抑制剂BMS-202在其线粒体和核调控作用上存在不一致性。我们还证实,线粒体转运蛋白具有巨大的潜力用于转运中药单体,而中药单体具有抗氧化作用,为本课题深入研究奠定了良好基础。.本课题获得的关键性突破是发现TSPO可以跨膜转运滋阴清热复方进入线粒体,在线粒体内发挥抗氧化作用,开启了滋阴清热复方甚至中药的线粒体领域的研究。相关文献正在投稿中。
滋阴清热法调控骨髓EMP对狼疮鼠抗核抗体和幼红细胞孤核免疫效应的作用及机理研究
  • 批准号:
    81673983
  • 项目类别:
    面上项目
  • 资助金额:
    52.0万元
  • 批准年份:
    2016
  • 负责人:
    程喜平
  • 依托单位:
以轻度狼疮活动梯次评估滋阴清热药对细胞焦亡负反馈调控效能
  • 批准号:
    81373649
  • 项目类别:
    面上项目
  • 资助金额:
    70.0万元
  • 批准年份:
    2013
  • 负责人:
    程喜平
  • 依托单位:
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