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竹节香附素 A(RA)通过抑制 TLR4 减轻了小鼠实验性脑出血的急性炎症损伤。

Raddeanin A (RA) reduced acute inflammatory injury in mouse experimental cerebral hemorrhage by suppression of TLR4.

机构信息

Department of neurosurgery, Peking University People's Hospital, Peking University, Beijing, China.

出版信息

Int J Med Sci. 2022 Jul 11;19(8):1235-1240. doi: 10.7150/ijms.73007. eCollection 2022.

Abstract

Spontaneous intracerebral hemorrhage (ICH) is associated with high mortality and disability rates. The microglia-induced inflammatory response is a critical factor determining brain tissue damage after ICH. Raddeanin A (RA) is a natural triterpenoid compound with anti-inflammatory effects, although its effects on ICH and the underlying molecular mechanism have not been elucidated. In this study, we found that RA reduced the volume of cerebral hematoma and cerebral edema, attenuated neuronal apoptosis and improved the behavioral indices in a murine model of acute cerebral hemorrhage. Mechanistically, RA downregulated the TLR4-mediated pro-inflammatory effectors, reduced infiltration of microglia in peri-intracerebral hemorrhage and inhibited apoptosis of neurons co-cultured with activated microglia. In conclusion, RA can alleviate ICH-related tissue damage and promote the recovery of neuronal function by suppressing microglia-induced inflammation and apoptosis.

摘要

自发性脑出血(ICH)与高死亡率和残疾率相关。小胶质细胞引发的炎症反应是决定 ICH 后脑组织损伤的关键因素。栀子苷 A(RA)是一种具有抗炎作用的天然三萜类化合物,但其对 ICH 的作用及其潜在的分子机制尚不清楚。在本研究中,我们发现 RA 可减少脑血肿和脑水肿的体积,减轻神经元凋亡,并改善急性脑出血小鼠模型的行为指标。在机制上,RA 下调 TLR4 介导的促炎效应物,减少脑出血周围小胶质细胞的浸润,并抑制与激活小胶质细胞共培养的神经元凋亡。总之,RA 可以通过抑制小胶质细胞引发的炎症和凋亡,减轻 ICH 相关的组织损伤并促进神经元功能的恢复。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ccc0/9346382/a657d33f3c28/ijmsv19p1235g001.jpg

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