SMCT1介导短链脂肪酸跨瘤胃转运在奶牛SARA发生发展中的作用机制
批准号:
32102742
项目类别:
青年科学基金项目(C类)
资助金额:
30.0 万元
负责人:
赵晨旭
依托单位:
学科分类:
临床兽医学
结题年份:
2024
批准年份:
2021
项目状态:
已结题
项目参与者:
赵晨旭
中文摘要
亚急性瘤胃酸中毒(SARA)是集约化奶牛养殖场常见的群发性生产疾病。瘤胃内短链脂肪酸(SCFA)生成增多和/或吸收障碍引起的SCFA蓄积是SARA的病理学基础,但其吸收障碍的原因尚不清楚。基于申请者前期证实SARA奶牛瘤胃上皮介导SCFA转运的重要分子Na+偶联单羧酸转运蛋白1(SMCT1)低表达,且高浓度的SCFA抑制SMCT1表达,本项目提出SARA病牛瘤胃SCFA的蓄积可能使SMCT1介导的SCFA转运功能异常,进而导致SCFA吸收障碍的科学假设。拟通过高精粗比日粮诱导奶牛SARA模型(在体)、尤斯灌流室(组织)和原代瘤胃上皮细胞体外培养(细胞)三个方面,明确SMCT1介导的SCFA跨瘤胃转运机制,探究SCFA蓄积引起瘤胃内pH下降,乳酸、LPS和组胺增加对SMCT1介导的SCFA转运的影响,为揭示SMCT1介导的SCFA跨瘤胃转运机制在SARA发生发展中的作用提供理论依据。
英文摘要
Subacute rumen acidosis (SARA) is a common mass production disease in intensive dairy farms. Accumulation of short-chain fatty acids (SCFA) in the rumen due to increased production and/or malabsorption is the pathological basis of SARA, but the cause of SCFA malabsorption remains unclear. Based on the applicant's previous confirmation that, sodium-coupled monocarboxylate transporter 1 (SMCT1), an important molecule of rumen epithelium mediated SCFA transport, was low expressed in SARA cows, and the expression of SMCT1 was inhibited by high concentration of SCFA. This project proposes that SCFA accumulation in rumen of SARA cows may cause SMCT1-mediated SCFA transport function abnormal, thus leading to the malabsorption of SCFA. This project intends to corroborate SMCT1 role in rumen epithelial SCFA transportation through establishing a SARA cows model induced by high concentrate diet (in vivo), Ussing chamber (organizations) and the primary culture of rumen epithelial cells in vitro (cells), which could clarify the mechanism of SMCT1 mediated SCFA across rumen transportation. This project will also investigate the effects of SCFA accumulation on rumen pH reduction and increase of lactic acid, LPS and histamine on SMCT1-mediated SCFA transport, which could provide a theoretical basis for revealing the function of SMCT1-mediated SCFA transport across rumen in the development of SARA.
随着我国奶牛养殖集约化和产奶量不断提高,奶牛亚急性瘤胃酸中毒(SARA)的发病率随之升高,造成严重经济损失。SARA的病理学基础在于瘤胃内短链脂肪酸(SCFA)生成增多和吸收障碍,而酸性环境破坏瘤胃内环境稳态,释放出内毒素(LPS)等物质导致瘤胃上皮炎症,并通过上皮屏障易位进入血液,诱发全身系统性炎症。因此,明确SARA时瘤胃上皮SCFA吸收障碍机理及炎症发生机制,是防治SARA的关键。本项目通过奶牛SARA在体和瘤胃上皮细胞体外模型,通过外源添加SCFA各组分及LPS模拟SARA条件下瘤胃代谢环境,检测转运蛋白SMCT1和炎症通路关键蛋白表达变化及炎症状态。结果显示,转运蛋白SMCT1在奶牛消化道上均有表达和分布,且SARA奶牛瘤胃上皮SMCT1表达下降,高浓度SCFA抑制其表达。添加丙酸铬可显著提高热应激奶牛产奶量,丙酸钙能改善乳品质,且二者均能调节瘤胃微生物群落结构。体外实验进一步阐明丙酸钠通过抑制NF-κB和MAPK信号通路缓解LPS诱导的瘤胃上皮细胞炎症的机制,并发现乳酸钠和低pH环境协同促进炎症因子产生。本项目成果不仅丰富了奶牛瘤胃生理与病理学研究,也为奶牛SARA和热应激的防治提供了新的策略,具有重要的科学意义和应用价值。
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海外基金