Kupffer细胞在肝纤维化发展和转归过程中吞噬能力变化的研究

The process of liver fibrosis can be reversed after timely diagnosis and effective treatment, accordingly to avoid liver cirrhosis or even liver cancer. Thus early diagnosis, treatment and assessment of liver fibrosis are particularly important. In our previous study, we found that Kupffer cells (KCs) might generate "Kupffer Phase" imaging by phagocytosis of ultrasound contrast agents, and further discovered significant decrease of enhancement level in fibrotic and cirrhotic liver, which presumably according to the decreased capacity of KCs phagocytosis. But so far, there was no direct evidence to prove that the liver enhancement level and KCs phagocytic activity have direct relationship. Thus in this study, we will produce different degree of liver fibrosis rats in progressive and reversal period, utilize inverted phase contrast microscope and immunohistochemical examination to observe the phagocytosis phenomenon of KCs, detect the regularity of KCs phagocytosis capacity changes during the progressive and reversal period of liver fibrosis. By examination of the KCs surface receptors, we will analyze the mechanisms of KCs on swallowing different substancesand. By combination with KCs phenotypes, we will further clarify the fuction of KCs during progressive and reversal process of liver fibrosis. If we prove that the enhancement level of liver, the fibrosis degree and KCs phagocytic capacity are directly related, we could provide substantial foundation of contrast-enhanced imaging in diagnosis and follow-up of liver fibrosis.

肝纤维化经过及时有效的治疗可得到逆转，避免肝硬化、甚至肝癌的发生，因此肝纤维化的及早诊治及疗效评估尤为重要。我们在前期研究中对大鼠进行Sonazoid超声造影，发现Kupffer细胞（KCs）可能通过特异性吞噬造影剂产生“Kupffer期”显像，并进一步发现纤维化、硬化肝脏增强水平逐步减低，推测是由KCs吞噬能力下降导致的。但目前没有证据表明肝脏增强水平与KCs吞噬能力直接相关。本研究将制作不同阶段肝纤维化大鼠模型，通过倒置相差显微镜及免疫组化等方法直接观测KCs吞噬多种物质的能力，系统的研究肝纤维化发展和转归过程中KCs吞噬能力的变化；并通过检测细胞表面受体分析KCs吞噬不同物质的机制；最终与KCs细胞表型相结合，进一步阐明KCs在肝纤维化发展及转归过程中所起的作用。若能证实肝脏增强水平、肝纤维化程度及KCs吞噬能力直接相关，将为增强影像学应用于肝纤维化无创诊断及疗效评估奠定坚实的基础。