中文摘要
术后出现腹腔粘连与腹腔免疫微环境的改变密切相关。腹腔巨噬细胞M1/M2极化表型决定腹腔免疫微环境变化后的腹腔炎症及组织纤维化反应趋势,而JAK/STAT/PPARγ信号通路调控M1/M2极化表型。前期研究结果表明:活血通腑方可通过下调腹腔CD40、CD40L和MCP-1蛋白水平及上调IL-10水平等有效降低术后粘连程度,推测其效应机制可能与介导JAK/STAT/PPARγ信号转导进而调控腹腔巨噬细胞M1/M2极化表型有关。为此,拟在腹腔粘连模型动物及腹腔巨噬细胞上,采用高通量高速成像流式技术量化分析潜在靶点PPARγ核转位水平及其通过JAK/SATA通路对巨噬细胞M1/M2极化状态的影响;运用细胞因子液相芯片技术分析粘连局部免疫微环境状态;重点研究并阐明活血通腑方对腹腔巨噬细胞极化及其介导免疫微环境变化的干预作用和分子效应机制,为进一步探讨术后腹腔粘连免疫机制及指导中医药有效防治提供依据。
英文摘要
Postoperative peritoneal adhesion is closely associated with the changes of peritoneal immune microenvironment. The M1/M2 polarization of peritoneal macrophages plays a key role of the development trend of peritoneal inflammation and tissue fibrosis after peritoneal immune microenvironment change. The JAK/STAT/PPARγ signal pathway regulates the state of M1/M2 polarization. Our previous studies have demonstrated that Blood-activating and Organ-purging formula effectively prevented postoperative peritoneal adhesion in animal models by up-regulating CD40、CD40L and MCP-1 protein levels , and down-regulating IL-10 protein levels, indicating that the therapeutic mechanisms may be involved in mediating the JAK/STAT/PPARγ signal transduction to regulate the state of macrophage M1/M2 polarization. Therefore, in animal models of peritoneal adhesion and cell models of peritoneal macrophages, this project will analysis the potential target PPARγ nuclear translocation level and the mediation of the JAK/SATA pathway to macrophage M1/M2 polarization by multispectral imaging flow cytometry; as well as detect the local immune microenvironment state of peritoneal adhesion by using xMAP technology. This project will mainly investigate and explore the intervention and the underlying molecular mechanism of Blood-activating and Organ-purging formula on peritoneal macrophage polarization and its mediated immune microenvironment change. These results from this study will provide the evidences for further exploring the immune mechanism of postoperative peritoneal adhesion, and guiding the effective prevention and treatment of traditional Chinese medicine.
