中文摘要
中医经典古方血府逐瘀汤具有活血祛瘀、行气止痛之功,临床用于治疗非酒精性脂肪肝(NAFLD)疗效确切,优势明显,但作用机制不清。LPS/p38MAKP通路在NAFLD的发病过程中发挥关键作用,其核心是趋化中性粒细胞浸润及后续微炎症损伤。前期研究发现,血府逐瘀汤可有效改善NAFLD模型小鼠肝脂肪变性,以减轻炎性细胞浸润为病理改善特点,同时可减少趋化因子MIP2和KC的表达;本方中引经药的不同配伍可影响其有效成分在肝组织中的分布。据此,提出“血府逐瘀汤可通过干预LPS/p38MAKP通路,对抗中性粒细胞浸润,阻断后续炎症损伤,发挥治疗NAFLD的作用,且该作用与引经药配伍有关”的研究假说。本研究拟通过建立体内外研究模型,采用IF、FCM、qRT-PCR、WB等技术,探索血府逐瘀汤对抗中性粒细胞浸润的作用规律和特点,探讨其不同配伍形式的抗中性粒细胞浸润作用与LPS/p38MAKP通路之间的相关性。
英文摘要
Xuefu Zhuyu Tang, a classic formula, can promote blood circulation to remove stasis and move qi to relieve pain. It has been proven effective in treating non-alcoholic fatty liver disease (NAFLD) with obvious advantages. However, its action mechanism is unclear. LPS/p38MAKP pathway is crucial in the pathogenesis of NAFLD, which is marked by neutrophil chemotaxis and infiltration and subsequent microinflammation damage. Our previous study revealed that Xuefu Zhuyu Tang can effectively improve the liver steatosis of NAFLD mice model by alleviating inflammatory cell infiltration typically and meanwhile reducing chemokine MIP2 and KC expression; and different combinations of its guiding herbs affect the distribution of its effective constituents in the hepatic tissue. Hereby, we would like to propose the hypothesis that "Xuefu Zhuyu Tang may intervene LPS/p38MAKP pathway to reduce neutrophils infiltration, interdict subsequent inflammatory injury, and treat NAFLD effectively; and its role is associated with different combination of guiding herbs". This study will establish in vitro and in vivo models and apply such techniques as IF, FCM, qRT-PCR and WB to explore the rules and features of Xuefu Zhuyu Tang's effect of reducing neutrophils infiltration and to investigate the correlation between LPS/p38MAKP pathway and the formula's effect of relieving neutrophil infiltration when herbs are combined in various ways.
