Department of Organ Transplantation, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Huangpu District, Shanghai, 200003, China.
Cell Biochem Biophys. 2014 Jun;69(2):347-55. doi: 10.1007/s12013-013-9806-2.
It has been well proved that acute inflammatory response and hepatocellular apoptosis contributed to the pathogenesis of liver ischemia reperfusion (IR) injury. A vast amount of research has demonstrated that magnesium lithospermate B (MLB) has potent anti-apoptosis and potential anti-inflammatory pharmacological properties. However, it has not previously been examined whether MLB can attenuate hepatic IR injury. Firstly, the optimal dose of MLB to protect against hepatic IR injury was determined using hepatic IR model in mice. Then, the effect of MLB on IR-induced inflammatory response was detected in detail. We found that MLB exhibited protective effect from the beginning of 50 mg/kg and culminated at the doses of 100 and 200 mg/kg. The alanine aminotransferase and aspartate aminotransferase levels in MLB group were markedly decreased. Severe hepatocellular swelling/necrosis, sinusoidal/vascular congestion and inflammatory cell infiltration were seen and a large number of apoptotic cells were found in the liver samples from Saline group, while minimal damage and very few apoptotic cells were noted in the samples from MLB group. Kuppfer cells infiltration, myeloperoxidase activity and mRNA level of CD11b in MLB group was significantly decreased. Serum TNF-a and IL-6, and mRNA expression of CXCL-10 and ICAM-1 was markedly decreased in the samples from MLB group. Inflammatory signaling pathway activation was largely prevented in MLB group. MLB can significantly attenuate IR-induced hepatocellular damage and hepatocellular apoptosis by preventing inflammatory signaling pathways activation, inflammatory mediators expression and macrophage and neutrophil infiltration.
已充分证实，急性炎症反应和肝细胞凋亡导致肝脏缺血再灌注（IR）损伤的发病机制。大量研究表明，镁 Lithospermate B（MLB）具有强大的抗凋亡和潜在的抗炎药理作用。然而，以前尚未研究过 MLB 是否可以减轻肝 IR 损伤。首先，使用小鼠肝 IR 模型确定了 MLB 保护肝免受 IR 损伤的最佳剂量。然后，详细检测了 MLB 对 IR 诱导的炎症反应的影响。我们发现，从 50mg/kg 开始，MLB 表现出保护作用，并在 100mg/kg 和 200mg/kg 时达到高峰。MLB 组的丙氨酸氨基转移酶和天冬氨酸氨基转移酶水平明显降低。在盐水组的肝组织切片中可见严重的肝细胞肿胀/坏死、窦状隙/血管充血和炎症细胞浸润，并且发现大量凋亡细胞，而在 MLB 组的组织切片中仅观察到最小的损伤和很少的凋亡细胞。MLB 组库普弗细胞浸润、髓过氧化物酶活性和 CD11b 的 mRNA 水平明显降低。在 MLB 组的血清 TNF-a 和 IL-6，以及 CXCL-10 和 ICAM-1 的 mRNA 表达明显降低。在 MLB 组中，炎症信号通路的激活被大大阻止。MLB 可通过防止炎症信号通路的激活、炎症介质的表达以及巨噬细胞和中性粒细胞的浸润，显著减轻 IR 诱导的肝细胞损伤和肝细胞凋亡。
