基于TLR4信号通路探索肠屏障损伤在大鼠酒精性肝损伤中的作用及参苓白术散的干预效应

Alcohol-induced intestinal barrier damage, LPS into the portal, enhanced expression of TLR4 signaling pathway, liver library fluorine NF-κB cell activation and inflammatory cytokines release in great quantities, cause liver damage, which is based on gut - liver axis theory in recent years put forward the important pathogenesis of ALD, intestinal barrier for target is a new train of thought, it is consistent with the "treating liver by nourishing spleen" in TCM in the level of theory connotation, but further study is not reported. Research shows that Shenlingbaizhu Powder can protect intestinal barrier and liver, speculated that the protection of intestinal barrier, to reduce enterogenous LPS, reduce TLR4 signal path expression is one of the mechanism of curative effect of ALD. In this research, observe the intestinal mucosa damage of rats with ALD, by means of the intestinal mucosa pathology and ultrastructure of SIgA, intestinal mucosa, intestinal bacteria amount; measuring serum ALT, AST and liver tissue pathologic to observe the liver injury; detecte the expression of gene and protein of liver tissue TLR4 and NF-κB cell, measuring the concentration of inflammatory factors such as serum TNF alpha, IL - 1, and observe the change of the above indicators by using Shenlingbaizhu Powder , to further clarify mechanism of intestinal mucosa injury of ALD and its based on TLR4 signaling pathways lead to liver damage, and further confirmed protective effect of Shenlingbaizhu Powder on the intestinal barrier ,as well as liver based on TLR4 signaling pathways.

酒精致肠屏障损伤，LPS大量进入门脉，TLR4信号通路表达增强，肝脏库普氟细胞NF-κB 等激活，炎性因子大量释放，造成肝损伤，这是近年基于肠-肝轴学说提出的ALD重要发病机制，以肠屏障为靶点是治疗ALD新思路，这与中医"脾实，肝自愈"理念一致，但进一步的深入研究未见报道。研究表明参苓白术散具有肠屏障保护及护肝作用，推测其保护肠屏障、减少肠源性LPS、降低TLR4信号通路表达是其对ALD疗效机制之一。课题从肠粘膜病理及超微结构、小肠粘膜SIgA、肠细菌量等观察ALD大鼠肠屏障损伤；测血浆ALT、AST、肝组织病理观察肝损伤；检测肝组织TLR4、NF-κB 等基因及蛋白表达，血浆TNF-α、IL -1等炎性因子浓度，并观察参苓白术干预后上述指标的变化，拟进一步阐明ALD肠屏障损伤及其基于TLR4信号通路导致肝损伤的机制，并进一步证实参苓白术散的肠屏障保护作用及其基于TLR4信号通路的护肝效应