Department of Heart Intensive Care Unit, The First Affiliated Hospital of Dalian Medical University, No.193 Lianhe Road, Dalian, China.
Department of Cardiology, Zhejiang Rongjun Hospital, No.309 Shuangyuan Road, Jiaxing, Zhejiang, China.
Inflammation. 2019 Apr;42(2):516-525. doi: 10.1007/s10753-018-0909-1.
Sepsis is a major health complication causing patient mortality and increased healthcare costs. Cardiac dysfunction, an important consequence of sepsis, affects mortality. We previously reported that thymoquinone (TQ) protected against hyperlipidemia and doxorubicin-induced cardiac damage. This study investigated the possible protective effects of TQ against cardiac damage in septic BALB/c mice. Eight-week-old male BALB/c mice were divided into four groups: control, TQ, cecal ligation and puncture (CLP), and TQ + CLP. CLP was performed after 2-week TQ gavage. After 48 h, we measured the histopathological alterations of the cardiac tissue and the plasma levels of troponin-T (cTnT) and ATP. We evaluated autophagy (p62 and beclin 1), pyroptosis (NLRP3, caspase-1, interleukin [IL]-1β, and IL-18) at the gene and protein levels and IL-6 and tumor necrosis factor-α (TNF-α) at the gene level. Our results demonstrated that TQ administration significantly reduced intestinal histological alterations. TQ inhibited plasma cTnT levels; improved ATP; significantly inhibited p62, NLRP3, caspase-1, IL-1β, IL-18, IL-6, TNF-α, and MCP-1expressions; and increased beclin 1 and IL-10 level. The phosphatidylinositide 3-kinase level was significantly decreased in the TQ + CLP group versus the CLP group. These results suggest that TQ effectively modulates autophagy, pyroptosis, and pro-inflammatory, making it important in the treatment of sepsis-induced cardiac damage.
脓毒症是一种主要的健康并发症，可导致患者死亡和增加医疗保健成本。心功能障碍是脓毒症的重要后果，影响死亡率。我们之前报道过，胸腺醌（TQ）可预防高血脂症和阿霉素引起的心脏损伤。本研究旨在探讨 TQ 对脓毒症 BALB/c 小鼠心脏损伤的可能保护作用。将 8 周龄雄性 BALB/c 小鼠分为四组：对照组、TQ 组、盲肠结扎穿孔（CLP）组和 TQ+CLP 组。CLP 在 TQ 灌胃 2 周后进行。48 小时后，我们测量了心脏组织的组织病理学改变以及肌钙蛋白 T（cTnT）和三磷酸腺苷（ATP）的血浆水平。我们评估了自噬（p62 和 beclin 1）、焦亡（NLRP3、caspase-1、白细胞介素[IL]-1β和 IL-18）在基因和蛋白水平以及 IL-6 和肿瘤坏死因子-α（TNF-α）在基因水平的表达。结果表明，TQ 给药可显著减轻肠道组织学改变。TQ 抑制血浆 cTnT 水平；提高 ATP；显著抑制 p62、NLRP3、caspase-1、IL-1β、IL-18、IL-6、TNF-α和单核细胞趋化蛋白-1（MCP-1）表达；增加 beclin 1 和 IL-10 水平。TQ+CLP 组的磷脂酰肌醇 3-激酶水平明显低于 CLP 组。这些结果表明，TQ 可有效调节自噬、焦亡和促炎作用，在治疗脓毒症引起的心脏损伤方面具有重要作用。
