Pien-Tze-Huang attenuates neuroinflammation in cerebral ischaemia-reperfusion injury in rats through the TLR4/NF-κB/MAPK pathway.
Pien-Tze-Huang attenuates neuroinflammation in cerebral ischaemia-reperfusion injury in rats through the TLR4/NF-κB/MAPK pathway.
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DOI：
10.1080/13880209.2021.1942926
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发表时间：
2021-12
影响因子：
3.8
通讯作者：
Huang M
中科院分区：
文献类型：
--
作者：
Zhang X;Zhang Q;Huang L;Liu M;Cheng Z;Zheng Y;Xu W;Lu J;Liu J;Huang M
偏紫黄(PTH)传统上用于治疗包括中风在内的各种炎症相关疾病。然而，关于甲状旁腺素在缺血性中风中的抗炎作用和可能的机制的文献尚未见报道。本研究旨在探讨甲状旁腺素对缺血性卒中的抗炎作用及其机制。雄性SD大鼠经灌胃给予甲状旁腺素(1 80 mg/kg)4 d后，阻断大脑中动脉2 h，再灌流2 h，造成脑缺血再灌注损伤。TLR4拮抗剂TAK242(3 mg/kg)于大脑中动脉结扎后1.5 h腹腔注射。采用MRI、HE染色、定量逆转录聚合酶链式反应、免疫印迹和免疫荧光等方法。PTH治疗可显著缩小MCAO大鼠脑梗塞体积(减少51%)，改善神经功能(减少33%)，减轻脑组织病理损害。还能降低损伤脑组织中IL-1β、IL-6、肿瘤坏死因子-α和单核细胞趋化蛋白-1的水平(分别降低70%、78%、60%和58%)，抑制小胶质细胞和星形胶质细胞的活化，降低损伤脑组织中iNOS和COX-2的蛋白表达。此外，甲状旁腺素还下调TLR4、MYD88和TRAF6的蛋白表达，减少NF-κB的表达和核转位，降低p-ERK1/2、p-JNK1/2和p-p38的蛋白表达。TAK-242对大脑中动脉阻塞大鼠也有类似的作用。然而，联合应用PTH和TAK-242并不能显著增强PTH的抗炎作用。甲状旁腺素通过部分通过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。
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. This study investigates the anti-inflammatory effects and its underlying mechanism of PTH on ischaemic stroke. 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. 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. 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.
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影响因子：
8
作者：
通讯作者：
--
TAK-242 是 Toll 样受体 4 的拮抗剂，可预防小鼠急性脑缺血/再灌注损伤。
DOI：
10.1038/jcbfm.2014.240
发表时间：
2015-03-31
期刊：
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
影响因子：
--
作者：
通讯作者：
--
中风引起的全身脑部炎症
影响因子：
48
作者：
Shi, Kaibin;Tian, De-Cai;Shi, Fu-Doug
通讯作者：
Shi, Fu-Doug
影响因子：
5.9
作者：
Gonzalo-Gobernado, Rafael;Irene Ayuso, Maria;Montaner, Joan
通讯作者：
Montaner, Joan
影响因子：
5.4
作者：
Zhang, Xiaoqin;Zhang, Yiping;Peng, Jun
通讯作者：
Peng, Jun