Wang Ziming, Wu Zihong, Miao Yifan, Hao Aohan, Chen Hao, Zhao Shuang, Luo Min, Guo Shihan, Liu Yingming, Lu Yun
Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Hubei University of Chinese Medicine, Wuhan, China.
Front Pharmacol. 2024 Mar 13;15:1373663. doi: 10.3389/fphar.2024.1373663. eCollection 2024.
The objective of this study is to systematically evaluate the effect of ligustrazine on animal models of ischemic stroke and investigate its mechanism of action. The intervention of ligustrazine in ischemic diseases research on stroke model animals was searched in the Chinese National Knowledge Infrastructure (CNKI), Wanfang Database (Wanfang), VIP Database (VIP), Chinese Biomedical Literature Database (CBM), Cochrane Library, PubMed, Web of Science, and Embase databases. The quality of the included literature was evaluated using the Cochrane risk of bias tool. The evaluation included measures such as neurological deficit score (NDS), percentage of cerebral infarction volume, brain water content, inflammation-related factors, oxidative stress-related indicators, apoptosis indicators (caspase-3), and blood-brain barrier (BBB) permeability (Claudin-5). A total of 32 studies were included in the analysis. The results indicated that ligustrazine significantly improved the neurological function scores of ischemic stroke animals compared to the control group (SMD = -1.84, 95% CI -2.14 to -1.55, < 0.00001). It also reduced the percentage of cerebral infarction (SMD = -2.97, 95% CI -3.58 to -2.36, < 0.00001) and brain water content (SMD = -2.37, 95% CI -3.63 to -1.12, = 0.0002). In addition, ligustrazine can significantly improve various inflammatory factors such as TNF-α (SMD = -7.53, 95% CI -11.34 to -3.72, = 0.0001), IL-1β (SMD = -2.65, 95% CI -3.87 to -1.44, < 0.0001), and IL-6 (SMD = -5.55, 95% CI -9.32 to -1.78, = 0.004). It also positively affects oxidative stress-related indicators including SOD (SMD = 4.60, 95% CI 2.10 to 7.10, = 0.0003), NOS (SMD = -1.52, 95% CI -2.98 to -0.06, = 0.04), MDA (SMD = -5.31, 95% CI -8.48 to -2.14, = 0.001), and NO (SMD = -5.33, 95% CI -8.82 to -1.84, = 0.003). Furthermore, it shows positive effects on the apoptosis indicator caspase-3 (SMD = -5.21, 95% CI -7.47 to -2.94, < 0.00001) and the expression level of the sex-related protein Claudin-5, which influences BBB permeability (SMD = 7.38, 95% CI 3.95 to 10.82, < 0.0001). Ligustrazine has been shown to have a protective effect in animal models of cerebral ischemic injury. Its mechanism of action is believed to be associated with the reduction of inflammation and oxidative stress, the inhibition of apoptosis, and the repair of BBB permeability. However, further high-quality animal experiments are required to validate these findings.
本研究的目的是系统评价川芎嗪对缺血性脑卒中动物模型的作用，并探讨其作用机制。在中国知网（CNKI）、万方数据库（Wanfang）、维普数据库（VIP）、中国生物医学文献数据库（CBM）、考克兰图书馆、PubMed、科学网（Web of Science）和Embase数据库中检索川芎嗪对脑卒中模型动物缺血性疾病研究的干预情况。使用考克兰偏倚风险工具评估纳入文献的质量。评估指标包括神经功能缺损评分（NDS）、脑梗死体积百分比、脑含水量、炎症相关因子、氧化应激相关指标、凋亡指标（半胱天冬酶 -3）和血脑屏障（BBB）通透性（Claudin -5）。共纳入32项研究进行分析。结果表明，与对照组相比，川芎嗪显著改善了缺血性脑卒中动物的神经功能评分（标准化均数差[SMD]= -1.84，95%置信区间[CI] -2.14至 -1.55，P<0.00001）。它还降低了脑梗死百分比（SMD = -2.97，95% CI -3.58至 -2.36，P<0.00001）和脑含水量（SMD = -2.37, 95% CI -3.63至 -1.12，P = 0.0002）。此外，川芎嗪可显著改善多种炎症因子，如肿瘤坏死因子 -α（TNF -α，SMD = -7.53，95% CI -11.34至 -3.72，P = 0.0001）、白细胞介素 -1β（IL -1β，SMD = -2.65，95% CI -3.87至 -1.44，P<0.0001）和白细胞介素 -6（IL -6，SMD = -5.55，95% CI -9.32至 -1.78，P = 0.004）。它还对氧化应激相关指标产生积极影响，包括超氧化物歧化酶（SOD，SMD = 4.60，95% CI 2.10至7.10，P = 0.0003）、一氧化氮合酶（NOS，SMD = -1.52，95% CI -2.98至 -0.06，P = 0.04）、丙二醛（MDA，SMD = -5.31，95% CI -8.48至 -2.14，P = 0.001）和一氧化氮（NO，SMD = -5.33，95% CI -8.82至 -1.84，P = 0.003）。此外，它对凋亡指标半胱天冬酶 -3（SMD = -5.21，95% CI -7.47至 -2.94，P<0.00001）以及影响血脑屏障通透性的紧密连接蛋白 -5（Claudin -5）的表达水平有积极作用（SMD = 7.38，95% CI 3.95至10.82，P<0.0001）。川芎嗪已被证明在脑缺血损伤动物模型中具有保护作用。其作用机制被认为与减轻炎症和氧化应激、抑制细胞凋亡以及修复血脑屏障通透性有关。然而，需要进一步的高质量动物实验来验证这些发现。
