Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, China.
Department of Neurosurgery, 904th Hospital of Joint Logistic Support Force of PLA, Wuxi Clinical College of Anhui Medical University, Wuxi, China.
J Cell Physiol. 2021 Oct;236(10):6920-6931. doi: 10.1002/jcp.30351. Epub 2021 Mar 31.
Subarachnoid hemorrhage (SAH) is a subtype of stroke with high mortality and morbidity due to the lack of effective therapy. Atorvastatin has been reported to alleviate early brain injury (EBI) following subarachnoid hemorrhage (SAH) via reducing reactive oxygen species, antiapoptosis, regulated autophagy, and neuroinflammation. Which was the related to the pyroptosis? Pyroptosis can be defined as a highly specific inflammatory programmed cell death, distinct from classical apoptosis and necrosis. However, the precise role of pyroptosis in atorvastatin-mediated neuroprotection following SAH has not been confirmed. The present study aimed to investigate the neuroprotection and potential molecular mechanisms of atorvastatin in the SAH-induced EBI via regulating neural pyroptosis using the filament perforation model of SAH in male C57BL/6 mice, and the hemin-induced neuron damage model in HT-22. Atorvastatin or vehicle was administrated 2 h after SAH and hemin-induced neuron damage. The mortality, neurological score, brain water content, and neuronal death were evaluated. The results show that the atorvastatin treatment markedly increased survival rate, neurological score, greater survival of neurons, downregulated the protein expression of NLRP1, cleaved caspase-1, interleukin-1β (IL-1β), and IL-18, which indicated that atorvastatin-inhibited pyroptosis and neuroinflammation, ameliorated neuron death in vivo/vitro subjected to SAH. Taken together, this study demonstrates that atorvastatin improved the neurological outcome in rats and reduced the neuron death by against neural pyroptosis and neuroinflammation.
蛛网膜下腔出血（SAH）是一种高死亡率和发病率的中风亚型，由于缺乏有效的治疗方法。已有报道称，阿托伐他汀通过减少活性氧、抗细胞凋亡、调节自噬和神经炎症，减轻蛛网膜下腔出血（SAH）后的早期脑损伤（EBI）。这与细胞焦亡有什么关系呢？细胞焦亡可以定义为一种高度特异的炎症程序性细胞死亡，与经典的细胞凋亡和坏死不同。然而，阿托伐他汀在 SAH 后通过调节神经细胞焦亡介导神经保护的确切作用尚未得到证实。本研究旨在通过使用雄性 C57BL/6 小鼠的 SAH 纤维穿孔模型和 HT-22 中的血红素诱导神经元损伤模型，研究阿托伐他汀在 SAH 诱导的 EBI 中的神经保护作用及其潜在的分子机制，即通过调节神经细胞焦亡。在 SAH 和血红素诱导的神经元损伤后 2 小时给予阿托伐他汀或载体。评估死亡率、神经评分、脑水含量和神经元死亡。结果表明，阿托伐他汀治疗显著提高了存活率、神经评分、更多神经元存活、下调 NLRP1、裂解的半胱天冬酶-1、白细胞介素-1β（IL-1β）和白细胞介素-18 的蛋白表达，这表明阿托伐他汀抑制了细胞焦亡和神经炎症，改善了体内/体外 SAH 引起的神经元死亡。总之，这项研究表明，阿托伐他汀通过对抗神经细胞焦亡和神经炎症，改善了大鼠的神经功能预后并减少了神经元死亡。
