Abstract

Context

Pien-Tze-Huang (PTH) is traditionally applied to treat various inflammation-related diseases including stroke. However, literature regarding the anti-inflammatory effects and possible mechanisms of PTH in ischaemic stroke is unavailable.

Objective

This study investigates the anti-inflammatory effects and its underlying mechanism of PTH on ischaemic stroke.

Materials and methods

Cerebral ischaemia-reperfusion injury was induced through 2 h middle cerebral artery occlusion (MCAO) followed by 24 h reperfusion in male Sprague-Dawley (SD) rats receiving oral pre-treatment with PTH (180 mg/kg) for 4 days. TLR4 antagonist TAK-242 (3 mg/kg) was injected intraperitoneally at 1.5 h after MCAO. MRI, HE staining, qRT-PCR, western blot, and immunofluorescence methods were employed.

Results

PTH treatment markedly reduced cerebral infarct volume (by 51%), improved neurological function (by 33%), and ameliorated brain histopathological damage in MCAO rats. It also reduced the levels of four inflammatory mediators including IL-1β (by 70%), IL-6 (by 78%), TNF-α (by 60%) and MCP-1 (by 58%); inhibited microglia and astrocyte activation; and decreased protein expression of iNOS and COX-2 in injured brains. Moreover, PTH down-regulated the protein expressions of TLR4, MyD88, and TRAF6; reduced the expression and nuclear translocation of NF-κB; and lowered the protein expressions of p-ERK1/2, p-JNK, and p-p38. Similar effects were observed in MCAO rats with TAK-242 treatment. However, combined administration of PTH and TAK-242 did not significantly reinforce the anti-inflammatory effects of PTH.

Discussion and conclusion

PTH improved cerebral ischaemia-reperfusion injury by inhibiting neuroinflammation partly via the TLR4/NF-κB/MAPK signalling pathway, which will help guide its clinical application.

中文翻译：

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片仔癀通过TLR4/NF-κB/MAPK通路减轻大鼠脑缺血再灌注损伤的神经炎症

摘要

语境

片仔癀(PTH) 传统上用于治疗各种炎症相关疾病，包括中风。然而，关于 PTH 在缺血性卒中的抗炎作用和可能机制的文献尚不可用。

客观的

本研究探讨了 PTH 对缺血性卒中的抗炎作用及其潜在机制。

材料和方法

通过 2 小时大脑中动脉闭塞 (MCAO) 诱导脑缺血再灌注损伤，然后在接受口服 PTH (180 mg/kg) 口服预处理 4 天的雄性 Sprague-Dawley (SD) 大鼠中进行 24 小时再灌注。在 MCAO 后 1.5 小时腹膜内注射 TLR4 拮抗剂 TAK-242 (3 mg/kg)。采用 MRI、HE 染色、qRT-PCR、蛋白质印迹和免疫荧光方法。

结果

PTH 治疗显着减少了 MCAO 大鼠的脑梗塞体积（51%），改善了神经功能（33%），并改善了脑组织病理学损伤。它还降低了四种炎症介质的水平，包括 IL-1β（降低 70%）、IL-6（降低 78%）、TNF-α（降低 60%）和 MCP-1（降低 58%）；抑制小胶质细胞和星形胶质细胞的活化；并降低受伤大脑中 iNOS 和 COX-2 的蛋白质表达。此外，PTH 下调 TLR4、MyD88 和 TRAF6 的蛋白表达；降低NF-κB的表达和核转位；并降低 p-ERK1/2、p-JNK 和 p-p38 的蛋​​白表达。在用 TAK-242 治疗的 MCAO 大鼠中观察到类似的效果。然而，PTH 和 TAK-242 的联合给药并未显着增强 PTH 的抗炎作用。

讨论与结论

PTH部分通过TLR4/NF-κB/MAPK信号通路抑制神经炎症，从而改善脑缺血再灌注损伤，有助于指导其临床应用。