瘤胃健康及稳态是奶牛高产的重要基石。申请人前期首次研究发现Bcl-2关联永生基因（BAG3）介导的细胞抗凋亡途径与瘤胃上皮稳态密切相关。然而，BAG3在瘤胃上皮细胞中发挥抗凋亡作用的分子机制尚不清楚。本项目在原代培养奶牛瘤胃上皮细胞基础上，基于BAG3介导的细胞线粒体凋亡途径，研究瘤胃上皮细胞增殖-凋亡失衡对BAG3和Bcl-2家族激活状况的影响，利用基因沉默、基因过表达、CRISPR/Cas9基因敲除等分子生物学技术，并结合细胞生物学、转录组学和代谢组学，在分子和细胞层面研究BAG3抗瘤胃上皮细胞凋亡及对下游通路的作用及影响机制，阐明BAG3介导奶牛瘤胃上皮细胞抗凋亡的调节机制，为维持奶牛瘤胃上皮健康和稳态提供新思路和分子调控靶点，为奶牛健康高效生产提供理论基础。

Rumen health and homeostasis are critical basis for high yield of dairy cows. Our previous study firstly found that Bcl-2 Associated Athanogene 3 (BAG3)-mediated cell anti-apoptotic pathway is closely related to rumen epithelial homeostasis. However, the molecular mechanism of its anti-apoptotic effect in rumen epithelial cells is unclear. Based on the mitochondrial apoptosis pathway mediated by BAG3, a rumen epithelial cell proliferation-apoptosis imbalance model will be used to investigate its effects on the activation of the BAG3 and Bcl-2 family in the primary cultured rumen epithelial cells of cows. Then, the anti-apoptotic mechanism of BAG3 in rumen epithelial cell under the molecular and cellular levels will be evaluated using gene silencing, gene overexpression, CRISPR/Cas9 gene knockdown and other molecular biology techniques, combined with cell biology, transcriptomics and metabolomics. And the molecular mechanism of the BAG3’s effects on downstream pathways will be also detected. The objective of this project is to elucidate the regulation mechanism of BAG3-mediated anti-apoptotic pathways in rumen epithelial cell of dairy cows, to provide new ideas and molecular regulatory targets for ensuring rumen epithelial health and homeostasis in dairy cows, and to provide theoretical knowledge for healthy and efficient production of dairy cows.