中文摘要
幽门螺杆菌(Hp)与肠型胃癌的发生密切相关,非可控性炎症起关键作用,缺乏有效的化学预防。温郁金二萜类化合物C(温C)是我们从温郁金中获得的新成份,前期研究表明Hp感染后,可活化NF-κB信号通道,引起非可控性炎症,导致肠化,NLRC5是NF-κB上游基因,在炎症中NF-κB与NLRC5呈负相关,而温C干预后,可下调NF-κB,NLRC5表达增加。NLRC5是新发现的NLR基因家族,但在Hp感染中仍为空白。因此,我们推测温C可能通过NLRC5/NF-κB通道抑制Hp诱导炎症及肠化。为了证明这种假说,我们通过稳定RNAi技术构建慢病毒载体转染GES-1细胞,NLRC5基因敲除小鼠,予Hp感染,从体外、体内实验层面分别研究NLRC5/NF-κB信号通路在胃炎/肠化生中的作用,阐明NLRC5在胃炎/肠化生中所涉及的信号通路和具体机制及温C的作用,揭示慢性胃炎向胃癌进展的机制及温C阻断该进展的靶点。
英文摘要
There are close relationship between Helicobacter Pylori (Hp) and intestinal-type gastric cancer, while nonresolving inflammation play a key role,chemical prevention is lacking. Radix curcumae (RC)-derived diterpenoid C is recently obtained from RC ether extract by us, and its chemical properties and constitution are different from curcumin and β-elemene. Our previous studies showed that Hp infection can bring to nonresolving inflammation and intestinal metaplasia through activating nuclear factor kappa B (NF-KB) signal pathway.NLRC5 is upstream gene of NF-KB, and in our pre-experiments, there is negative correlation between NF-KB and NLRC5. We have shown that NLRC5 was upregulated and NF-KB was downregulated in human gastric mucosa after RC-derived diterpenoid C intervene.NLRC5 is a new member of the NLR family and was recently reported to be upstream gene of NF-KB. NLRC5 play an important role in proliferation, inflammation, and so on. But its function remains unclear in Hp infection. So we assume that RC-derived diterpenoid C could inhibit the Hp-induced inflammation and intestinal metaplasia through NLRC5. This program aims to explore the hypothesis by structuring lentiviral vector transfection GES-1 cell, NLRC5 gene knockout mice, and discuss the underlying molecular mechanism of NLRC5 modulating inflammation and intestinal metaplasia through NF-KB pathway, and clarify the pathway and mechanism of NLRC5 and target of RC-derived diterpenoid C. Therefore, it might provide new insights for the pathophysiology of chronic gastritis to gastric carcinogenesis and new target of RC-derived diterpenoid C blocking the carcinomatous change.
