Wang Jun, Guo Ming, Ma Ruojia, Wu Maolin, Zhang Yamei
Department of Cardiology, Zhejiang Xiaoshan Hospital, Hangzhou, Zhejiang Province, China.
Department of Acupuncture, Zhejiang Provincial Integrated Chinese and Western Medicine Hospital, Hangzhou, Zhejiang Province, China.
PeerJ. 2020 May 7;8:e9042. doi: 10.7717/peerj.9042. eCollection 2020.
BACKGROUND & AIMS: Tetrandrine (Tet) has been reported to have anti-inflammatory effects and protect from the ischemic strokes. The NLRP3 inflammasome plays a key role in cerebral ischemia/reperfusion (I/R)-induced inflammatory lesions. However, the molecular mechanisms of Tet related to the progression of cerebral ischemia are still unclear. Therefore, the aim of this study was to investigate the possible effects of Tet on cerebral ischemia and the related mechanisms involved in NLRP3 inflammasome.
C57BL/6J mice used as a cerebral I/R injury model underwent middle cerebral artery occlusion (MCAO) for 2 h following reperfusion for 24 h. Tet (30 mg/kg/day, ) was administered for seven days and 30 min before and after MCAO. Their brain tissues were evaluated for NLRP3 inflammasome and Sirtuin-1 (Sirt-1) expression. An intracerebroventricular injection of Sirt-1 siRNA was administered to assess the activation of the NLRP3 inflammasome.
Tet significantly reduced the neurological deficits, infarction volume, and cerebral water content in MCAO mice. Moreover, it inhibited I/R-induced over expression of NLRP3, cleaved caspase-1, interleukin (IL)-1β, IL-18, and Sirt-1. Sirt-1 knockdown with siRNA greatly blocked the Tet-induced reduction of neurological severity score and infarct volume, and reversed the inhibition of NLRP3 inflammasome activation.
Our results demonstrate that Tet has benefits for cerebral I/R injury, which are partially related to the suppression of NLRP3 inflammasome activation via upregulating Sirt-1.
据报道，粉防己碱（Tet）具有抗炎作用，并可预防缺血性中风。NLRP3炎性小体在脑缺血/再灌注（I/R）诱导的炎性损伤中起关键作用。然而，Tet与脑缺血进展相关的分子机制仍不清楚。因此，本研究旨在探讨Tet对脑缺血的可能影响以及NLRP3炎性小体相关的机制。
将C57BL/6J小鼠作为脑I/R损伤模型，进行大脑中动脉闭塞（MCAO）2小时，再灌注24小时。在MCAO前后30分钟给予Tet（30mg/kg/天），持续7天。评估其脑组织中NLRP3炎性小体和沉默调节蛋白1（Sirt-1）的表达。通过脑室内注射Sirt-1 siRNA来评估NLRP3炎性小体的激活情况。
Tet显著降低了MCAO小鼠的神经功能缺损、梗死体积和脑含水量。此外，它抑制了I/R诱导的NLRP3、裂解的半胱天冬酶-1、白细胞介素（IL）-1β、IL-18和Sirt-1的过度表达。用siRNA敲低Sirt-1大大阻断了Tet诱导的神经严重程度评分和梗死体积的降低，并逆转了对NLRP3炎性小体激活的抑制。
我们的结果表明，Tet对脑I/R损伤有益，这部分与通过上调Sirt-1抑制NLRP3炎性小体激活有关。
