有机阴离子转运蛋白SLC22A在SARA引起的瘤胃短链脂肪酸蓄积中的作用

Subacute ruminal acidosis (SARA), is a common disease for fattening cattle and sheep, is characterized by short chain fatty acids (SCFA) accumulation in the rumen.Ruminal SCFA accumulation was resulted from SCFA excess production and malabsorption. However, the few studies was fcuosed on the molecule mechanism of SCFA malabsorption. SLC22A, an organic anion transport protein, plays an important role in the uptake of SCFA in the ruminal epithelium cell. SCFA accumulation could induce low pH, which may infulence with the uptake of SCFA medicated by SLC22A. In this study, sheep with SARA and ruminal epithelium cell cultured in vitro were used. The expressions,distribution,and cellular localization of SLC22A in the ruminal epithelium were detected.The effects of HCO3- on the SCFA transport medicated by SLC22A were determinated, which revealed HCO3- could infulence with the SCFA transport through SLC22A. The effects of SCFA accumulation on the expression of SLC22A and SCFA uptake in the ruminal epithelium were detected, which indicated that low pH affected the SCFA transport medicated by SLC22A. This study will provide valuable information to understand the role of SLC22A in the SCFA accumulation induced by SARA.

亚急性瘤胃酸中毒(SARA)是育肥牛羊常见多发疾病，其特征是瘤胃短链脂肪酸(SCFA)蓄积。SCFA蓄积的主要原因是生成增加和吸收障碍，目前还不清楚瘤胃SCFA吸收障碍的原因和机制。SLC22A作为有机阴离子转运蛋白在瘤胃上皮SCFA吸收过程中发挥重要作用，而在瘤胃SCFA蓄积形成的低pH状态下，有可能改变瘤胃上皮SLC22A介导的SCFA吸收模式。本项目拟通过诱发绵羊SARA在体实验和模拟SARA体外实验，观测SLC22A家族成员在瘤胃上皮的表达、分布和细胞定位；观测HCO3-对瘤胃上皮SLC22A介导的SCFA转运的影响，证实SLC22A介导的SCFA转运是否依赖HCO3-；观测SCFA蓄积对瘤胃上皮SLC22A家族成员表达的影响及其与SCFA吸收的关系，确认瘤胃pH降低可干扰SLC22A介导的SCFA转运。为揭示SLC22A在SARA所致的瘤胃SCFA蓄积中的作用提供理论基础。

亚急性瘤胃酸中毒(SARA)是牛羊生产中常见多发疾病，其特征是瘤胃短链脂肪酸(SCFAs)蓄积。SCFAs 蓄积的主要原因是生成增加和吸收障碍，目前瘤胃SCFAs吸收障碍的原因和机制还不清楚。有机阴离子转运蛋白在瘤胃上皮SCFAs吸收过程中发挥重要作用，因此，了解SARA时影响瘤胃上皮SCFAs转运的因素和机制，是治疗SARA的关键。本项目运用分子生物学和细胞生物学技术，通过在体和体外实验揭示SARA时瘤胃内pH降低，SCFAs的蓄积可以引起瘤胃上皮细胞炎症反应，造成细胞的炎性损伤，破坏瘤胃上皮的相关机能；完成SCFAs转运蛋白SLC22A家族（A7、A9、A4和A5）、SLC5A8和MCT1在牛消化道上的定位，确证转运蛋白在瘤胃上皮组织各部位的表达情况；揭示SARA时瘤胃上皮组织中SCFAs转运蛋白表达受到抑制；体外细胞刺激实验进一步证明低浓度SCFAs促进转运蛋白表达，高浓度抑制表达；低pH环境以及高浓度LPS也会影响转运蛋白的表达水平。瘤胃SCFAs蓄积是导致SARA发生发展的关键病理环节，而SCFAs的转运又是解决问题的关键，本研究从健康和病理角度检测了几种关键转运蛋白的变化情况，为阐明SCFAs转运机制在SARA中的作用提供理论基础。