HMB通过Akt-FoxO3a信号通路缓解免疫应激仔猪肌肉蛋白质降解的机制研究

Increased protein degradation in skeletal muscle induced by immune stress is one of the important factors that leads to the growth depression of piglets, causing great economic loss in swine production. How to attenuate the immune stress-induced muscular protein degradation in piglets has become an important issue to increase the economic benefits of pig production. The current research indicates that leucine can significantly promote protein synthesis, which is mediated by its metabolite beta-hydroxy-beta-methylbutyrate (HMB). Meanwhile, HMB has an ability to inhibit muscle atrophy. Our previous studies showed that dietary HMB supplementation could decrease the rate of muscular protein degradation in piglets, and it works better than leucine. However, the mechanism of action of HMB remains to be determined. Hence, through the establishment of immune stress model induced by lipopolysaccharide (LPS) in vivo and in vitro and the use of Akt inhibitors and FoxO3a siRNA, this study aims to investigate the effects of HMB on growth performance and muscular protein degradation of piglets, together with the regulation mechanism of HMB on Akt-FoxO3a signaling pathway and its downstream molecules expression. The research results will reveal the effect and regulation mechanism of HMB on muscular protein degradation of piglets, which will provide nutritional regulation means for promoting growth performance of piglets, and will lay a theoretical foundation for the exploitation and utilization of HMB.

免疫应激引起的肌肉蛋白质降解加快是导致仔猪生长迟缓的重要因素之一，给养猪生产造成重大经济损失。如何缓解免疫应激仔猪的肌肉蛋白质降解，已成为提高养猪生产效益的重要课题。现有研究表明，亮氨酸可显著促进机体蛋白质的合成，且其中间代谢产物β-羟基-β-甲基丁酸（HMB）介导了该调控过程。同时，HMB还具有抑制肌肉萎缩的作用。项目申请人前期研究发现，HMB能够降低仔猪肌肉蛋白质降解速率，且作用效果优于亮氨酸，但其作用机制尚不清楚。因此，本项目拟通过脂多糖（LPS）诱导仔猪免疫应激，考察HMB对其生长性能和肌肉组织蛋白质降解的影响；并采用HMB、Akt抑制剂和FoxO3a小干扰RNA处理LPS应激肌细胞，检测Akt-FoxO3a信号通路及其下游效应蛋白的表达，旨在揭示HMB缓解免疫应激仔猪肌肉蛋白质降解的分子机制，为提高仔猪的生长性能提供营养调控手段，并为HMB的开发利用奠定理论基础。

免疫应激引起的肌肉蛋白质降解加快是导致仔猪生长迟缓的重要因素之一，给养猪生产造成重大经济损失。如何缓解免疫应激仔猪的肌肉蛋白质降解，已成为提高养猪生产效益的重要课题。现有研究表明，亮氨酸可显著促进机体蛋白质的合成，且其中间代谢产物β-羟基-β-甲基丁酸（beta-Hydroxy-beta-methylbutyrate，HMB）介导了该调控过程。同时，HMB还具有抑制肌肉萎缩的作用。项目申请人前期研究发现，HMB能够降低仔猪肌肉蛋白质降解速率，且作用效果优于亮氨酸，但其作用机制尚不清楚。据此，本项目通过脂多糖（LPS）诱导仔猪免疫应激，考察HMB对其生长性能和肌肉组织蛋白质降解的影响；并采用HMB、Akt抑制剂和FoxO3a小干扰RNA处理LPS应激肌细胞，检测Akt-FoxO3a信号通路及其下游效应蛋白的表达，旨在揭示HMB缓解免疫应激仔猪肌肉蛋白质降解的分子机制。研究结果显示，HMB可通过调节Akt/FoxO3a信号通路以抑制泛素化蛋白降解途径，来缓解由LPS诱导的慢性免疫应激断奶仔猪肌肉蛋白质降解，且仔猪日粮中HMB适宜添加剂量为0.60%。本研究结果为促进免疫应激仔猪肌肉生长提供营养调控手段，并为HMB的开发利用奠定了理论基础。

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