Abstract：
BACKGROUND: Cerebral ischemia is a common disease that seriously threatens the health of human beings. Tanshinone IIA (TSA) is a fat-soluble compound isolated from the traditional Chinese medicine Danshen. Recent studies have shown that TSA plays a significant protective role in the animal models of cerebral ischemic injury.
OBJECTIVE: The meta-analysis was to evaluate the protective effect of Danshen (Salvia miltiorrhiza Bunge) extract (TSA) in cerebral ischemic injury, aiming at providing scientific evidence for clinical application of TSA in the treatment of cerebral ischemia in patients.
METHODS: All relevant studies published in PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database, Chinese Scientific Journals Database (VIP) and Chinese Biomedicine Database (CBM) before Jan 2023 were systematically retrieved. The methodological quality was assessed by SYRCLE\'s risk of bias tool for the animal studies. Data was analyzed using Rev Man 5.3 software.
RESULTS: A total of 13 studies were included. Compared with the control group, TSA significantly reduced the expression of glial fibrillary acidic protein (GFAP) (mean difference [MD], -1.78; 95% CI, [-2.13, -1.44]; P < 0.00001) and high mobility group protein B1 (HMGB1) (MD, -0.69; 95% CI, [-0.87, -0.52]; P < 0.00001). TSA also inhibited the activation of brain nuclear factor κB (NF-κB) (MD, - 0.36; 95% CI, [-0.41, -0.32]; P < 0.00001), malondialdehyde (MDA) (MD, -0.90; 95% CI, [-1.66, -0.13]; P = 0.02), cysteine protease-3 (Caspase-3) (MD, -1.39; 95% CI, [-1.98, -0.81]; P < 0.00001), and reduced cerebral infarction volume(MD, -16.26; 95% CI, [-20.76, -11.77]; P < 0.00001), brain water content (MD, -4.89; 95% CI, [-7.06, -2.71]; P < 0.0001) and neurological deficit scores (MD, -1.19; 95% CI, [-1.48, -0.89]; P < 0.00001). Additionally, TSA increased the brain content of superoxide dismutase (SOD) (MD, 68.31; 95% CI, [10.41, 126.22]; P = 0.02).
CONCLUSIONS: The result of this study showed that TSA had a protective effect on cerebral ischemic injury in animal models, and the mechanism is associated with the reduction of inflammation and oxidative stress, and the inhibition of cell apoptosis. However, the quality of included studies may affect the accuracy of positive results. Therefore, more high-quality randomized controlled animal experiments are need for meta-analysis in the future.
OBJECTIVE: The meta-analysis was to evaluate the protective effect of Danshen (Salvia miltiorrhiza Bunge) extract (TSA) in cerebral ischemic injury, aiming at providing scientific evidence for clinical application of TSA in the treatment of cerebral ischemia in patients.
METHODS: All relevant studies published in PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database, Chinese Scientific Journals Database (VIP) and Chinese Biomedicine Database (CBM) before Jan 2023 were systematically retrieved. The methodological quality was assessed by SYRCLE\'s risk of bias tool for the animal studies. Data was analyzed using Rev Man 5.3 software.
RESULTS: A total of 13 studies were included. Compared with the control group, TSA significantly reduced the expression of glial fibrillary acidic protein (GFAP) (mean difference [MD], -1.78; 95% CI, [-2.13, -1.44]; P < 0.00001) and high mobility group protein B1 (HMGB1) (MD, -0.69; 95% CI, [-0.87, -0.52]; P < 0.00001). TSA also inhibited the activation of brain nuclear factor κB (NF-κB) (MD, - 0.36; 95% CI, [-0.41, -0.32]; P < 0.00001), malondialdehyde (MDA) (MD, -0.90; 95% CI, [-1.66, -0.13]; P = 0.02), cysteine protease-3 (Caspase-3) (MD, -1.39; 95% CI, [-1.98, -0.81]; P < 0.00001), and reduced cerebral infarction volume(MD, -16.26; 95% CI, [-20.76, -11.77]; P < 0.00001), brain water content (MD, -4.89; 95% CI, [-7.06, -2.71]; P < 0.0001) and neurological deficit scores (MD, -1.19; 95% CI, [-1.48, -0.89]; P < 0.00001). Additionally, TSA increased the brain content of superoxide dismutase (SOD) (MD, 68.31; 95% CI, [10.41, 126.22]; P = 0.02).
CONCLUSIONS: The result of this study showed that TSA had a protective effect on cerebral ischemic injury in animal models, and the mechanism is associated with the reduction of inflammation and oxidative stress, and the inhibition of cell apoptosis. However, the quality of included studies may affect the accuracy of positive results. Therefore, more high-quality randomized controlled animal experiments are need for meta-analysis in the future.
摘要：
背景：脑缺血是严重威胁人类健康的常见疾病。丹参酮IIA（TSA）是一种从中药丹参中分离的脂溶性化合物。最近的研究表明，TSA在脑缺血损伤的动物模型中起着重要的保护作用。
目的：评价丹参提取物(TSA)对脑缺血损伤的保护作用。旨在为TSA治疗脑缺血患者的临床应用提供科学依据。
方法：所有相关研究发表在PubMed，WebofScience,科克伦图书馆,中国国家知识基础设施(CNKI),万方数据库,系统检索了2023年1月之前的中国科学期刊数据库（VIP）和中国生物医学数据库（CBM）。通过SYRCLE的动物研究偏倚风险工具评估方法学质量。使用RevMan5.3软件分析数据。
结果：共纳入13项研究。与对照组相比,TSA显著降低胶质纤维酸性蛋白（GFAP）的表达（均差[MD]，-1.78；95％CI，[-2.13，-1.44]；P<0.001）和高迁移率族蛋白B1（HMGB1）（MD，-0.69；95%CI，[-0.87，-0.52]；P<0.001）。TSA还抑制了脑核因子κB（NF-κB）的激活（MD，-0.36；95%CI，[-0.41，-0.32]；P<0.001），丙二醛（MDA）（MD，-1.19；95%CI，[-1.48，-0.89]；P<0.001），半胱氨酸蛋白酶-3(Caspase-3)(MD，-1.39；95%CI，[-1.98，-0.81]；P<0.001），和减少脑梗死体积（MD，-16.26；95%CI，[-20.76，-11.77]；P<0.001），大脑含水量(MD，-4.89；95%CI，[-7.06，-2.71]；P<0.001）和神经功能缺损评分（MD，-1.19；95%CI，[-1.48，-0.89]；P<0.001）。此外,TSA增加了大脑中超氧化物歧化酶（SOD）的含量（MD，68.31；95%CI，[10.41，126.22]；P=0.02）。
结论：这项研究的结果表明，TSA对动物模型的脑缺血损伤具有保护作用，机制与减少炎症和氧化应激有关，抑制细胞凋亡。然而,纳入研究的质量可能会影响阳性结果的准确性.因此,未来需要更多高质量的随机对照动物实验进行荟萃分析.
目的：评价丹参提取物(TSA)对脑缺血损伤的保护作用。旨在为TSA治疗脑缺血患者的临床应用提供科学依据。
方法：所有相关研究发表在PubMed，WebofScience,科克伦图书馆,中国国家知识基础设施(CNKI),万方数据库,系统检索了2023年1月之前的中国科学期刊数据库（VIP）和中国生物医学数据库（CBM）。通过SYRCLE的动物研究偏倚风险工具评估方法学质量。使用RevMan5.3软件分析数据。
结果：共纳入13项研究。与对照组相比,TSA显著降低胶质纤维酸性蛋白（GFAP）的表达（均差[MD]，-1.78；95％CI，[-2.13，-1.44]；P<0.001）和高迁移率族蛋白B1（HMGB1）（MD，-0.69；95%CI，[-0.87，-0.52]；P<0.001）。TSA还抑制了脑核因子κB（NF-κB）的激活（MD，-0.36；95%CI，[-0.41，-0.32]；P<0.001），丙二醛（MDA）（MD，-1.19；95%CI，[-1.48，-0.89]；P<0.001），半胱氨酸蛋白酶-3(Caspase-3)(MD，-1.39；95%CI，[-1.98，-0.81]；P<0.001），和减少脑梗死体积（MD，-16.26；95%CI，[-20.76，-11.77]；P<0.001），大脑含水量(MD，-4.89；95%CI，[-7.06，-2.71]；P<0.001）和神经功能缺损评分（MD，-1.19；95%CI，[-1.48，-0.89]；P<0.001）。此外,TSA增加了大脑中超氧化物歧化酶（SOD）的含量（MD，68.31；95%CI，[10.41，126.22]；P=0.02）。
结论：这项研究的结果表明，TSA对动物模型的脑缺血损伤具有保护作用，机制与减少炎症和氧化应激有关，抑制细胞凋亡。然而,纳入研究的质量可能会影响阳性结果的准确性.因此,未来需要更多高质量的随机对照动物实验进行荟萃分析.
