Department of Traditional Chinese Medicine, Wuxi 9th People's Hospital Affiliated to Soochow University Wuxi, Jiangsu 214000, P. R. China.
Department of Critical Care Medicine, Wuxi 9th People's Hospital Affiliated to Soochow University Wuxi, Jiangsu 214000, P. R. China.
Am J Chin Med. 2023;51(8):2157-2173. doi: 10.1142/S0192415X23500921. Epub 2023 Oct 20.
Hemorrhagic shock (HS) is the leading cause of death in trauma patients. Inflammation following HS can lead to cardiac damage. Pachymic acid (PA), a triterpenoid extracted from , has been found to possess various biological activities, including anti-inflammatory and anti-apoptotic properties. Our research aims to investigate the protective effects of PA against HS-induced heart damage and the underlying mechanisms involved. Male Sprague-Dawley rats were intraperitoneally injected with PA (7.5 or 15[Formula: see text]mg/kg) daily for three days. Subsequently, we created a rat model of HS by drawing blood through a catheter inserted into the femoral artery followed by resuscitation. The results revealed that HS led to abnormalities in hemodynamics, serum cardiac enzyme levels, and cardiac structure, as well as induced cardiac apoptosis. However, pretreatment with PA effectively alleviated these effects. PA-pretreatment also suppressed mRNA and protein levels of interleukin (IL)-1[Formula: see text], IL-6, and tumor necrosis factor [Formula: see text] (TNF-[Formula: see text]) in the heart tissues of HS rats. Additionally, PA-pretreatment reduced inflammatory cell infiltration and M1 macrophage polarization while exaggerating M2 polarization in HS rat hearts. The study observed a decreased proportion of the expression of of M1 macrophages (CD86[Formula: see text]) and their marker (iNOS), along with an increased proportion of the expression of M2 macrophages (CD206[Formula: see text]) and their marker (Arg-1). Notably, PA-pretreatment suppressed NF-[Formula: see text]B pathway activation via inhibiting NF-[Formula: see text]B p65 phosphorylation and its nuclear translocation. In conclusion, PA-pretreatment ameliorates HS-induced cardiac injury, potentially through its inhibition of the NF-[Formula: see text]B pathway. Therefore, PA treatment holds promise as a strategy for mitigating cardiac damage in HS.
失血性休克（HS）是创伤患者死亡的主要原因。HS 后炎症可导致心脏损伤。从 中提取的五环三萜酸（PA）已被发现具有多种生物活性，包括抗炎和抗细胞凋亡作用。我们的研究旨在探讨 PA 对 HS 诱导的心脏损伤的保护作用及其潜在机制。雄性 Sprague-Dawley 大鼠每天腹膜内注射 PA（7.5 或 15[Formula: see text]mg/kg）连续三天。随后，我们通过从股动脉插入的导管抽血并进行复苏来建立 HS 大鼠模型。结果表明，HS 导致血液动力学异常、血清心脏酶水平和心脏结构异常，并诱导心脏细胞凋亡。然而，PA 预处理可有效缓解这些作用。PA 预处理还抑制了 HS 大鼠心脏组织中白细胞介素（IL）-1[Formula: see text]、IL-6 和肿瘤坏死因子 [Formula: see text]（TNF-[Formula: see text]）的 mRNA 和蛋白水平。此外，PA 预处理减少了 HS 大鼠心脏中的炎症细胞浸润和 M1 巨噬细胞极化，同时增强了 M2 极化。研究观察到 M1 巨噬细胞（CD86[Formula: see text]）及其标志物（iNOS）的表达比例降低，而 M2 巨噬细胞（CD206[Formula: see text]）及其标志物（Arg-1）的表达比例增加。值得注意的是，PA 预处理通过抑制 NF-[Formula: see text]B p65 磷酸化及其核易位抑制 NF-[Formula: see text]B 通路的激活。总之，PA 预处理可改善 HS 诱导的心脏损伤，可能通过抑制 NF-[Formula: see text]B 通路。因此，PA 治疗可能成为减轻 HS 中心脏损伤的一种策略。
