The pathogenesis of brain injury caused by carbon monoxide poisoning (COP) is very complex, and there is no exact and reliable treatment in clinic. In the present study, we screened the therapeutic target and related signal pathway of Salvia Miltiorrhiza for acute COP brain injury, and clarified the pharmacological mechanism of multicomponent, multitarget, and multisignal pathway in Salvia Miltiorrhiza by network pharmacology. To further verify the therapeutic effect of Salvia Miltiorrhiza on acute brain injury based on the results of network analysis, a total of 216 male healthy Sprague Dawley rats were collected in the present study and randomly assigned to a normal control group, a COP group and a Tanshinone IIA sulfonate treatment group (72 rats in each group). The rat model of acute severe COP was established by the secondary inhalation in a hyperbaric oxygen chamber. We found that Salvia Miltiorrhiza had multiple active components, and played a role in treating acute brain injury induced by COP through multiple targets and multiple pathways, among them, MAPK/ERK1/2 signaling pathway was one of the most important. COP can start apoptosis process, activate the MAPK/ERK1/2 signaling pathway, and promote the expression of VEGF-A protein and the formation of brain edema. Tanshinone IIA can effectively inhibit apoptosis, up-regulate the expressions of VEGF-A, P-MEK1/2 and P-ERK1/2 proteins, thereby protect endothelial cells, promote angiogenesis and microcirculation, and finally alleviate brain edema.

中文翻译：

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基于互联网药理学策略的丹参对一氧化碳中毒大鼠急性脑损伤的治疗作用及分子机制

一氧化碳中毒（COP）引起的脑损伤的发病机制非常复杂，临床上尚无确切可靠的治疗方法。本研究筛选丹参治疗急性COP脑损伤的治疗靶点及相关信号通路，并通过网络药理学阐明丹参多成分、多靶点、多信号通路的药理机制。为了根据网络分析的结果进一步验证丹参对急性脑损伤的治疗作用，本研究共收集216只雄性健康SD大鼠，随机分为正常对照组、COP组和对照组。丹参酮IIA磺酸盐治疗组(每组72只)。采用高压氧舱二次吸入法建立急性重症COP大鼠模型。我们发现丹参具有多种活性成分，通过多靶点、多途径发挥治疗COP所致急性脑损伤的作用，其中MAPK/ERK1/2信号通路是其中最重要的信号通路之一。COP可以启动细胞凋亡过程，激活MAPK/ERK1/2信号通路，促进VEGF-A蛋白的表达和脑水肿的形成。丹参酮IIA能有效抑制细胞凋亡，上调VEGF-A、P-MEK1/2和P-ERK1/2蛋白的表达，从而保护内皮细胞，促进血管生成和微循环，最终缓解脑水肿。