Abstract：
High-concentrate diet can cause metabolic diseases, such as subacute ruminal acidosis (SARA), and secondary mastitis. To investigate the effect of SARA induced by high-concentrate diet on the lysine lactylation (Kla) and inflammatory responses in the mammary gland of dairy cows and the mechanism between them, we selected twelve mid-lactation Holstein cows with similar body conditions for modelling. They were randomly divided into two groups, fed a low-concentrate diet (LC) and a high-concentrate diet (HC) for 21 days. Our results showed that high-concentrate diet feeding significantly reduced ruminal pH, and the pH was below 5.6 for more than 3 h per day, indicating successful induction of the SARA model. Lactic acid concentrations in mammary gland and plasma were higher in the HC group than that in the LC group. HC diet feeding significantly up-regulated the expression levels of the Pan Kla, H3K18la, p300/CBP and monocarboxylate transporter 1 (MCT1) in the mammary gland. In addition, the mRNA expression levels of inflammatory factors were significantly regulated, including IL-1β, IL-1α, IL-6, IL-8, SAA3, and TNF-α, while the anti-inflammatory factor IL-10 was down-regulated. The mammary gland of HC group was structurally disorganized with incomplete glandular vesicles, with a large number of detached mammary epithelial cells and inflammatory cells infiltration. The up-regulation of TLR4, TNF-α, p-p65, and p-IκBα indicated that the TLR4/NF-κB signaling pathway was activated. In conclusion, this study found that HC diet feeding can induce SARA and increase the concentration of lactic acid in mammary gland and plasma. Then, lactic acid could be transported into cells by MCT1 and up-regulate the expression level of histone lactylation mediated by p300/CBP, and subsequently promote the activation of TLR4/NF-κB signaling pathway, ultimately causing inflammatory responses in the mammary gland.
摘要：
高浓度饮食会导致代谢性疾病，如亚急性瘤胃酸中毒（SARA），和继发性乳腺炎.探讨高浓缩日粮中添加SARA对奶牛乳腺内赖氨酸乳酸化(Kla)及炎性反应的影响及其机制。我们选择了12头具有相似身体状况的哺乳期中期荷斯坦奶牛进行建模。他们被随机分为两组,饲喂低浓饮食（LC）和高浓饮食（HC）21天。我们的结果表明，高浓缩饮食显著降低瘤胃pH值，和pH值低于5.6每天超过3小时，表明SARA模型的成功诱导。HC组乳腺和血浆中的乳酸浓度高于LC组。HC饮食喂养显着上调了PanKla的表达水平，H3K18la,乳腺中的p300/CBP和单羧酸转运蛋白1（MCT1）。此外,炎症因子的mRNA表达水平显著受调控,包括IL-1β，IL-1α,IL-6、IL-8、SAA3和TNF-α，而抗炎因子IL-10下调。HC组乳腺结构紊乱，腺泡不完整，乳腺上皮细胞大量脱落及炎性细胞浸润。TLR4、TNF-α、p-p65和p-IκBα表明TLR4/NF-κB信号通路被激活。总之,本研究发现，HC饮食喂养可以诱导SARA并增加乳腺和血浆中的乳酸浓度。然后，乳酸可以通过MCT1转运到细胞中,上调p300/CBP介导的组蛋白的表达水平,进而促进TLR4/NF-κB信号通路的激活,最终导致乳腺炎症反应。
