褪黑素通过其受体调控绵羊亚急性瘤胃酸中毒黏膜损伤的机制

亚急性瘤胃酸中毒（SARA）是影响反刍动物生产的重要疾病之一，其瘤胃上皮炎性病变是瘤胃内菌群失调的代谢产物刺激引起的。褪黑素有抗氧化和其受体介导的抗炎作用。项目组前期研究发现瘤胃黏膜能合成褪黑素和有其受体的表达。基于以上，推测褪黑素可以通过其受体调控抑制瘤胃黏膜损伤。为此本项目拟建立绵羊SARA模型，应用高效液相色谱（HPLC）和组织学技术系统研究瘤胃内褪黑素和受体表达的动态变化与亚急性酸中毒发病和治愈的相关性；建立SCFA/LPS/His诱导瘤胃上皮炎性细胞模型，采用免疫印迹、实时荧光定量PCR、酶联免疫吸附等技术检测通过褪黑素受体影响TLR4/NF-κB通路炎性因子及相关蛋白的表达，同时研究褪黑素抗瘤胃黏膜上皮细胞氧化损伤、细胞凋亡和对上皮细胞紧密连接蛋白表达的调控作用。这为阐明褪黑素调控亚急性酸中毒引发的瘤胃黏膜损伤机制和利用其为反刍动物亚急性瘤胃酸中毒的防治提供基础性研究。

Abstract: Subacute rumen acidosis (SARA) is one of the most important diseases that affect the production of ruminants. The dermatitis in the rumen epithelial cells is caused by the stimulation of metabolites of dysbacteriosis in the rumen. Melatonin has antioxidant and receptor-mediated anti-inflammatory effects. Previous studies of the project team found that the rumen mucosa can synthesize melatonin and have its receptor expression. Based on the above, It is speculated that melatonin can inhibit rumen mucosal injury through its receptor regulation. Therefore, the project plans to establish sheep subacute rumen acidosis models, and systematically study the dynamic changes of melatonin and its receptor expression in the rumen during the onset and cure of subacute rumen acidosis by using high performance liquid chromatography (HPLC) and histological techniques; establish cell models of SCFA/LPS/His induced rumen epithelial dermatitis, and detect inflammatory factors and related proteins by using western blotting, real-time fluorescent quantitative PCR and enzyme-linked immunosorbent assay in TLR4/NF-κB pathway regulating through melatonin receptor; and to study the effects of melatonin on oxidative damage, apoptosis and tight junction protein expression of rumen epithelial cells. This study will provide a basic research for elucidating the mechanism of melatonin regulating rumen mucosal injury induced by subacute rumen acidosis and using it to prevent and treat subacute acidosis in ruminants.