Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
Mol Neurobiol. 2024 May;61(5):2904-2920. doi: 10.1007/s12035-023-03724-x. Epub 2023 Nov 10.
Neuroinflammation caused by microglia in the central nervous system (CNS) is observed after myocardial infarction (MI). However, the inflammatory response mechanism remains unclear. BuChang Naoxintong capsule (NXT) is a Chinese medicine for treating ischemic cardio-cerebrovascular diseases, requiring more studies to understand the pharmacodynamic mechanism. Permanent ligation of the left anterior descending coronary artery (LAD) was performed in rats. Additionally, histopathological staining in the left ventricular (LV) and immunofluorescence within the brain cortex after 1 d and 7 d of MI were performed to determine the NXT pharmacodynamic action and best administration dosage. Proteomics helped obtain the essential proteins related to neuroinflammation and MI in the heart and brain tissue after 7 d of MI. Based on TTC, HE, Masson, and immunofluorescence staining results of CD206 and IBA-1, NXT demonstrated a better pharmacodynamic action towards myocardial injury and neuroinflammation after 7 d of MI. Moreover, the human equivalent dosage of NXT (220 mg/kg) became the best administration dose. The proteome bioinformatics analysis in the LV and brain cortex was performed. Thus, the elongation of very long-chain fatty acids protein 5 (ELOVL5) and ATP-binding cassette subfamily G member 4 (ABCG4) became critical proteins related to MI and neuroinflammation. The western blotting results indicated that ABCG4 expression possessed the same trend as the proteomics results. The auto-dock results revealed that ABCG4 had a good binding ability with Ferulic acid, Paeoniflorin, and Tanshinone II A, the key ingredients of NXT. The cellular thermal shift assay results demonstrated that ABCG4 showed better thermal stability post-NXT treatment. NXT can improve myocardial injury, such as heart infarct size, pathological injury, myocardial fibrosis, and inflammatory cell infiltration. Additionally, brain neuroinflammation induced by microglia after MI affects the expression and structure of ABCG4. Thus, ABCG4 could be the key protein associated with MI and neuroinflammation.
脑内小胶质细胞引起的神经炎症反应在心肌梗死后（MI）中被观察到。然而，炎症反应的机制仍不清楚。步长脑心通胶囊（NXT）是一种治疗缺血性心脑血管疾病的中药，需要更多的研究来了解其药效学机制。在大鼠中进行左前降支（LAD）永久性结扎，在 MI 后 1 天和 7 天对左心室（LV）进行组织病理学染色，并对大脑皮层进行免疫荧光染色，以确定 NXT 的药效作用和最佳给药剂量。蛋白质组学帮助获得了 MI 后 7 天心脏和脑组织中与神经炎症和 MI 相关的关键蛋白。基于 TTC、HE、Masson 和 CD206 和 IBA-1 的免疫荧光染色结果，NXT 在 MI 后 7 天对心肌损伤和神经炎症表现出更好的药效作用。此外，NXT 的人体等效剂量（220mg/kg）成为最佳给药剂量。对 LV 和大脑皮层进行蛋白质组学生物信息学分析。因此，延伸非常长链脂肪酸蛋白 5（ELOVL5）和三磷酸腺苷结合盒亚家族 G 成员 4（ABCG4）成为与 MI 和神经炎症相关的关键蛋白。Western blot 结果表明，ABCG4 的表达与蛋白质组学结果具有相同的趋势。自动对接结果表明，ABCG4 与 NXT 的关键成分阿魏酸、芍药苷和丹参酮 IIA 具有良好的结合能力。细胞热转移测定结果表明，NXT 处理后 ABCG4 表现出更好的热稳定性。NXT 可改善心肌损伤，如心肌梗死面积、病理损伤、心肌纤维化和炎症细胞浸润。此外，MI 后小胶质细胞引起的脑神经炎症会影响 ABCG4 的表达和结构。因此，ABCG4 可能是与 MI 和神经炎症相关的关键蛋白。
