Oleanolic acid rejuvenates testicular function through attenuating germ cell DNA damage and apoptosis via deactivation of NF-κB, p53 and p38 signalling pathways
Oleanolic acid rejuvenates testicular function through attenuating germ cell DNA damage and apoptosis via deactivation of NF-κB, p53 and p38 signalling pathways
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齐墩果酸通过使 NF-κB、p53 和 p38 信号通路失活来减轻生殖细胞 DNA 损伤和细胞凋亡，从而恢复睾丸功能。
DOI：
10.1111/jphp.12668
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发表时间：
2017-03-01
影响因子：
3.3
通讯作者：
Zhang, Changcheng
中科院分区：
文献类型：
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作者：
Zhao, Haixia;Liu, Jing;Zhang, Changcheng
目的 炎症可导致生殖功能的退行性改变。齐墩果酸（OA）是女贞子中的有效成分，具有显着的抗炎和抗衰老活性。然而，OA是否通过抑制衰老过程中的炎症来恢复睾丸功能障碍尚不清楚。在此，我们在自然衰老大鼠模型中研究了OA的保护作用及其作用机制。方法将18个月大的SD大鼠随机分为衰老对照组和两个OA治疗组（5和25 mg/kg）。九个月大的 SD 大鼠用作成年对照。所有大鼠均接受赋形剂或 OA 治疗 6 个月。然后检查睾丸的组织形态学、重量和指数、蛋白质表达和免疫组织化学。 主要发现齐墩果酸显着恢复睾丸形态并改善睾丸重量和指数。此外，OA显着抑制睾丸组织中磷酸-NF-κB p65及其下游促炎细胞因子的表达，包括IL-1β、COX-2和TNF-α。同样，OA 显着抑制 IL-1 β 和 TNF-α 的产生。 OA 显着减弱生殖细胞的 DNA 损伤和细胞凋亡。这种变化伴随着 H2AX、p-P53 和 Bax 表达的下调，以及 Bcl-2 和 Bcl-2/Bax 比率的上调。此外，OA还显着抑制p38信号传导。结论齐墩果酸通过灭活NF-kappa B、p53和p38信号通路，减轻生殖细胞DNA损伤和细胞凋亡，从而有效恢复睾丸功能。
Objectives Inflammation can cause degenerative changes of reproductive function. Oleanolic acid (OA), the effective component from Ligustrum lucidum Ait., exhibits significantly anti-inflammation and antiageing activity. However, whether OA restores testicular dysfunction via inhibition of inflammation with ageing is unclear. Here, in a natural ageing rat model, we investigated the protection effects of OA and its mechanism of action.Methods Eighteen-month-old Sprague Dawley (SD) rats were randomly divided into ageing control group and two OA-treated groups (5 and 25 mg/kg). Nine-month-old SD rats were used as adult controls. All rats were received either vehicle or OA for 6 months. Then, histomorphology, weight and index of testis, protein expression and immunohistochemistry were examined.Key findings Oleanolic acid significantly restored testicular morphology and improved testicular weight and index. Moreover, OA significantly inhibited phospho-NF-kappa B p65 and its downstream proinflammatory cytokines' expressions, including IL-1 beta, COX-2 and TNF-alpha in testis tissues. Similarly, OA remarkably inhibited IL-1 beta and TNF-alpha production. OA significantly attenuated germ cells' DNA damage and apoptosis. Such changes were accompanied by downregulation of H2AX, p-P53 and Bax expressions, and upregulation of Bcl-2 and Bcl-2/Bax ratio. In addition, OA remarkably inhibited p38 signalling.Conclusions Oleanolic acid effectively rejuvenates testicular function via attenuating germ cell DNA damage and apoptosis through deactivation of NF-kappa B, p53 and p38 signalling pathways.