肠渗漏是酒精性肝病（ALD）的主要原因之一，辣椒素具有抑制肠渗漏的作用，但机制有待进一步阐明。辣椒素受体（TRPV1）表达与肠病变关系密切，我们前期发现：辣椒素对野生型酒精肝小鼠肠细胞Caspase3表达增高和TRPV1表达降低有显著调控作用，而对TRPV1-/-酒精肝Caspase3升高无抑制作用。因此，提出“辣椒素调控肠细胞TRPV1/caspase3信号抑制酒精性脂肪肝”的科学假说；拟采用实时定量PCR和膜片钳等技术，研究酒精对Caco-2细胞TRPV1基因表达、调控作用，运用RNA干扰和流式细胞仪等技术，明确TRPV1对Caspase3活性和紧密连接的影响及辣椒素的干预作用；进而运用Lieber-DeCarli复合Binge酒精肝模型，研究TRPV1-/-小鼠肠细胞凋亡与ALD进展及辣椒素的干预作用。本项目的完成有助于发现辣椒素抑制ALD的分子机制，为其治疗开辟新途径。

Intestinal leakage plays a major role in the alcoholic liver disease. Capsaicin can inhibit intestinal leakage, but the mechanism needs to be further clarified. The expression of transient receptor potential vanilloid type-1 (TRPV1) is closely related to intestinal disease. Our previous study found that TRPV1 was down-regulated and Caspase3 was up-regulated in alcohol-induced liver injury WT mice, on which capsaicin has significantly regulatory effects. However, it cannot restrain the over-expression of Caspase3 when TRPV1 were knock-down. Based on these new findings, we could hypothesize that Capsaicin inhibit alcoholic fatty liver disease by regulating TRPV1/caspase3 signal transduction in enterocyte. We would utilize real-time PCR analysis and patch clamp technique to elucidate the effect of alcohol on the expression and regulation of TRPV1 in Caco-2 cells. Simultaneously, we would study the effect of TRPV1 on Casase3 activity and the intervention of capsaicin using RNA interference and flow cytometry. Furthermore, we would use the Lieber-DeCarli plus Binge alcohol liver disease model to explore the intervention of capsaicin on intestinal cell apoptosis and ALD progression in TRPV1-/- mice. This project will help us find the molecular mechanism of capsaicin inhibiting ALD, which provides a new therapeutic strategy for clinical treatment.