Guanxinning, a modern Chinese medicine preparation composed of Salviae Miltiorrhizae Radix et Rhizoma and Chuanxiong Rhizoma, has the activities of activating blood circulation, resolving blood stasis, dredging vessels, and nourishing the heart. Clinical studies have demonstrated that Guanxinning has therapeutic effect on ischemic stroke, while the specific mechanism remains to be clarified. In this study, the potential mechanism of Guanxinning against cerebral ischemia-reperfusion injury in mice was explored and then verified in vitro. The mouse model of cerebral ischemia-reperfusion injury was established with middle cerebral artery embolization(MCAO) method. The pharmacological effects of Guanxinning on the model mice were investigated based on neurological function score, cerebral infarction area, pathological morphology, neuron injury, and apoptosis. The results showed that Guanxinning lowered neurological functional score, reduced cerebral infarction area, and ameliorated the histopathological morphology, neuronal damage, and apoptosis in the model mice. RNA samples were extracted from brain tissues and subjected to RNA sequencing(RNA-seq). The differentially expressed genes(DEGs) were screened with the thresholds of ■. GO function enrichment analysis and KEGG pathway enrichment analysis were performed for the 297 common DEGs, which indicated that Guanxinning may regulate the inflammatory response, oxidative stress response, energy metabolism, and apoptosis to treat cerebral ischemia-reperfusion injury in mice. Guanxinning exerted protective effect through inhibiting inflammation and reducing oxidative stress in hypoxia/reoxygenation injured SH-SY5 Y cells. Furthermore, Western blot indicated that Guanxinning down-regulated the protein levels of p-NF-κB p65 and p-p38 MAPK and up-regulated those of PPARγ and PGC-1α. The findings suggested that Guanxinning may inhibit inflammation and reduce oxidative stress by suppressing TNF signaling pathway and activating PPAR signaling pathway, thereby exerting the therapeutic effect on cerebral ischemia-reperfusion injury in mice. This study preliminarily reveals the mechanism of Guanxinning against cerebral ischemia-reperfusion injury and provides a basis for clinical application of Guanxinning.

中文翻译：

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基于转录组学分析的冠心宁抗小鼠脑缺血再灌注损伤机制[J].

冠心宁是由丹参和川芎组成的现代中药制剂，具有活血化瘀、疏通血管、养心的作用。临床研究表明冠心宁对缺血性脑卒中具有治疗作用，但具体机制尚待阐明。本研究探索冠心宁抗小鼠脑缺血再灌注损伤的潜在机制，并进行体外验证。采用大脑中动脉栓塞(MCAO)法建立小鼠脑缺血再灌注损伤模型。根据神经功能评分、脑梗死面积、病理形态学、神经元损伤、和细胞凋亡。结果表明，冠心宁降低了模型小鼠的神经功能评分，减少了脑梗死面积，改善了组织病理学形态、神经元损伤和细胞凋亡。从脑组织中提取RNA样本并进行RNA测序（RNA-seq）。以■为阈值筛选差异表达基因（DEGs）。对297个常见的DEGs进行GO功能富集分析和KEGG通路富集分析，表明冠心宁可能通过调节炎症反应、氧化应激反应、能量代谢和细胞凋亡来治疗小鼠脑缺血再灌注损伤。冠心宁通过抑制炎症和减少缺氧/复氧损伤SH-SY5 Y细胞的氧化应激发挥保护作用。此外，Western blot显示冠心宁下调p-NF-κB p65和p-p38 MAPK蛋白水平，上调PPARγ和PGC-1α蛋白水平。研究结果表明，冠心宁可能通过抑制TNF信号通路和激活PPAR信号通路抑制炎症，减轻氧化应激，从而发挥对小鼠脑缺血再灌注损伤的治疗作用。本研究初步揭示冠心宁抗脑缺血再灌注损伤的作用机制，为冠心宁的临床应用提供依据。研究结果表明，冠心宁可能通过抑制TNF信号通路和激活PPAR信号通路抑制炎症，减轻氧化应激，从而发挥对小鼠脑缺血再灌注损伤的治疗作用。本研究初步揭示冠心宁抗脑缺血再灌注损伤的作用机制，为冠心宁的临床应用提供依据。研究结果表明，冠心宁可能通过抑制TNF信号通路和激活PPAR信号通路抑制炎症，减轻氧化应激，从而发挥对小鼠脑缺血再灌注损伤的治疗作用。本研究初步揭示冠心宁抗脑缺血再灌注损伤的作用机制，为冠心宁的临床应用提供依据。