Hunan University of Chinese Medicine, Changsha 410208, Hunan, China; Key Laboratory of TCM Diagnostics of Hunan Provine, Changsha 410208, Hunan, China; Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Changsha 410208, Hunan, China.
Hunan University of Chinese Medicine, Changsha 410208, Hunan, China.
J Ethnopharmacol. 2024 Jan 10;318(Pt B):116990. doi: 10.1016/j.jep.2023.116990. Epub 2023 Aug 1.
Ischemic stroke poses a serious risk to public health and quality of life. Jie-Du-Huo-Xue decoction (JDHXD) is a classical and well-known Chinese formula for stroke treatment, but the pharmacological mechanism is still unclear.
This study aims to investigate the mechanism underlying microglial pyroptosis and polarization, as well as the potential efficacy of JDHXD against cerebral ischemia-reperfusion injury (CIRI).
Models of CIRI were established by the middle cerebral artery occlusion/reperfusion (MCAO/R) method in rats. In the first stage, 36 SD rats were randomly divided into sham group, I/R group, JDHXD-L group (5.36 g/kg/day), JDHXD-M group (10.71 g/kg/day), JDHXD-H group (21.42 g/kg/day), and positive drug edaravone group. The effectiveness of JDHXD on CIRI was confirmed by neurological function testing and cerebral infarct measuring. The best dose (JDXHD-M) was subsequently chosen to perform the tests that followed. In the second stage, 36 SD rats were randomly divided into the sham group, the I/R group, and the JDHXD-M group. Detection of nerve damage using Nissl staining, proteins of pyroptosis, Iba-1, and NeuN expressions were detected by western blotting, and proteins of microglial pyroptosis and M1/M2 phenotypic polarization were detected by immunofluorescence.
In rats after CIRI, JDHXD significantly reduced neurological impairment and cerebral infarction. In addition, JDHXD facilitated the M1-to-M2 transition of microglia in order to minimize neuroinflammation and improve anti-inflammatory repair. In addition, JDXHD inhibited microglial pyroptosis by blocking the cleavage of caspase-1 P10 and gasdermin D, hence reducing neuronal damage and enhancing neuronal survival following reperfusion. Interestingly, JDHXD also demonstrated a protective effect on the glial-vascular unit (GVU).
Our investigation demonstrated that JDHXD exerted a GVU-protective effect on CIRI rats by decreasing neuroinflammation-associated microglial pyroptosis, suppressing microglial M1 activation, and promoting microglial M2 activation.
缺血性中风对公众健康和生活质量构成严重威胁。解热毒活血汤（JDHXD）是一种经典且著名的中风治疗中药方剂，但药理机制尚不清楚。
本研究旨在探讨小胶质细胞细胞焦亡和极化的机制，以及 JDHXD 对脑缺血再灌注损伤（CIRI）的潜在疗效。
通过大脑中动脉闭塞/再灌注（MCAO/R）法建立 CIRI 模型。在第一阶段，将 36 只 SD 大鼠随机分为假手术组、I/R 组、JDHXD-L 组（5.36g/kg/天）、JDHXD-M 组（10.71g/kg/天）、JDHXD-H 组（21.42g/kg/天）和阳性药物依达拉奉组。通过神经功能测试和脑梗死测量来确认 JDHXD 对 CIRI 的疗效。随后选择最佳剂量（JDHXD-M）进行后续测试。在第二阶段，将 36 只 SD 大鼠随机分为假手术组、I/R 组和 JDHXD-M 组。通过尼氏染色检测神经损伤，通过 Western blot 检测细胞焦亡、Iba-1 和 NeuN 表达的蛋白，通过免疫荧光检测小胶质细胞细胞焦亡和 M1/M2 表型极化的蛋白。
在 CIRI 后的大鼠中，JDHXD 显著减轻神经损伤和脑梗死。此外，JDHXD 促进小胶质细胞 M1 向 M2 转化，以最大限度地减少神经炎症并促进抗炎修复。此外，JDHXD 通过阻断半胱氨酸天冬氨酸蛋白酶-1 P10 和 Gasdermin D 的裂解抑制小胶质细胞细胞焦亡，从而减少再灌注后神经元损伤和促进神经元存活。有趣的是，JDHXD 对神经血管单元（GVU）也表现出保护作用。
我们的研究表明，JDHXD 通过减少与神经炎症相关的小胶质细胞细胞焦亡、抑制小胶质细胞 M1 激活和促进小胶质细胞 M2 激活，对 CIRI 大鼠发挥 GVU 保护作用。
