绿茶多酚通过调节紧密连接和 PKCalpha 信号通路缓解实验性局灶性脑缺血早期的血脑屏障损伤。

BACKGROUND

It has been supposed that green tea polyphenols (GTPs) have neuroprotective effects on brain damage after brain ischemia in animal experiments. Little is known regarding GTPs' protective effects against the blood-brain barrier (BBB) disruption after ischemic stroke. We investigated the effects of GTPs on the expression of claudin-5, occludin, and ZO-1, and the corresponding cellular mechanisms involved in the early stage of cerebral ischemia.

METHODS

Male Wistar rats were subjected to a middle cerebral artery occlusion (MCAO) for 0, 30, 60, and 120 min. GTPs (400 mg/kg/day) or vehicle was administered by intragastric gavage twice a day for 30 days prior to MCAO. At different time points, the expression of claudin-5, occludin, ZO-1, and PKCα signaling pathway in microvessel fragments of cerebral ischemic tissue were evaluated.

RESULTS

GTPs reduced BBB permeability at 60 min and 120 min after ischemia as compared with the vehicle group. Transmission electron microscopy also revealed that GTPs could reverse the opening of tight junction (TJ) barrier at 60 min and 120 min after MACO. The decreased mRNA and protein expression levels of claudin-5, occludin, and ZO-1 in microvessel fragments of cerebral ischemic tissue were significantly prevented by treatment with GTPs at the same time points after ischemia in rats. Furthermore, GTPs could attenuate the increase in the expression levels of PKCα mRNA and protein caused by cerebral ischemia.

CONCLUSIONS

These results demonstrate that GTPs may act as a potential neuroprotective agent against BBB damage at the early stage of focal cerebral ischemia through the regulation of TJ and PKCα signaling.

背景

已有动物实验表明，绿茶多酚（GTP）对脑缺血后脑损伤具有神经保护作用。但对于 GTP 对缺血性中风后血脑屏障（BBB）破坏的保护作用知之甚少。我们研究了 GTP 对 Claudin-5、occludin 和 ZO-1 的表达的影响，以及在脑缺血早期涉及的相应细胞机制。

方法

雄性 Wistar 大鼠进行大脑中动脉闭塞（MCAO），时间分别为 0、30、60 和 120 分钟。GTP（400mg/kg/天）或载体通过灌胃每天两次给药，在 MCAO 前 30 天。在不同时间点，评估缺血性脑组织微血管片段中 Claudin-5、occludin、ZO-1 和 PKCα 信号通路的表达。

结果

与载体组相比，GTP 可降低缺血后 60 分钟和 120 分钟时的 BBB 通透性。透射电镜也显示，GTP 可逆转 MACO 后 60 分钟和 120 分钟时 TJ 屏障的开放。GTP 在缺血后相同时间点处理可显著防止 Claudin-5、occludin 和 ZO-1 在缺血性脑组织微血管片段中的 mRNA 和蛋白表达水平降低。此外，GTP 可减轻缺血引起的 PKCα mRNA 和蛋白表达水平的增加。