白藜芦醇通过HIF-1α/BNIP3介导的自噬信号通路促进小鼠缺氧性脑损伤修复

Protective effect and mechanism of resveratrol on hypoxic brain injury in mice

目的 探讨白藜芦醇通过HIF-1α/BNIP3介导的自噬信号通路促进小鼠缺氧性脑损伤修复的作用机制。方法 利用CQY-1型小动物缺氧检测系统建立小鼠间歇性缺氧模型。检测小鼠缺氧耐受时间、呼吸频率和心率变化。组织病理学染色检测大鼠脑组织形态学改变。Western blot方法检测小鼠脑组织中HIF-1α、P53、BNIP3、Beclin 1、LC3、P62的蛋白表达水平。结果 与缺氧组比,白藜芦醇能够延长小鼠缺氧耐受时间,增大缺氧小鼠的呼吸频率,降低缺氧小鼠的心率,缓解海马区脑组织损伤,下调HIF-1α、P53、Beclin 1、LC3蛋白表达,上调P62蛋白表达。结论 白藜芦醇下调HIF-1α/BNIP3介导的自噬信号通路,达到促进小鼠缺氧性脑损伤修复的作用。

Objective To investigate the effect of resveratrol on the repair of hypoxic brain injury through the HIF-1α/BNIP3-mediated autophagy signaling pathway in mice. Methods A mouse model of intermittent hypoxia was established using the CQY-1 small animal hypoxia detection system. The hypoxia tolerance time, respiratory rate, and heart rate changes of the mice were detected. Histopathological staining was used to detect morphological changes to the mice brain. Western blot was used to detect the protein expression levels of HIF-1α, P53, BNIP3, Beclin 1, LC3 and P62 in mice brain tissue. Results Compared with the findings in the hypoxia group, resveratrol prolonged the hypoxia tolerance time;increased the respiratory rate and reduced the heart rate of hypoxic mice;alleviate brain tissue damage in the hippocampus;down-regulated HIF-1α, P53, Beclin 1 and LC3 protein expression;and up-regulated P62 protein expression. Conclusions Resveratrol down-regulates HIF-1α/BNIP3-mediated autophagy signaling pathway gene expression to promote the repair of hypoxic brain injury in mice.