Zhou Panyu, Ma Bing, Xu Shuogui, Zhang Shijie, Tang Hongtai, Zhu Shihui, Xiao Shichu, Ben Daofeng, Xia Zhaofan
Burn Institute of Chinese People's Liberation Army and Department of Burn Surgery, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.
Cell Biochem Biophys. 2014 Nov;70(2):1265-75. doi: 10.1007/s12013-014-0050-1.
Sepsis is a common and critical complication in surgical patients that often leads to multiple organ failure syndrome (MOFS), including acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Despite intensive supportive care and treatment modalities, the mortality of these patients remains high. In this study, we investigated the role of Burton's tyrosine kinase (BTK), a member of the Btk/Tec family of cytoplasmic tyrosine kinases, in the pathogenesis of sepsis, and evaluated the protective effect of in vivo Btk RNA interference in a mouse model of cecal ligation and puncture (CLP)-induced sepsis. After intratracheal injection of Btk siRNA, the mice were then subjected to CLP to induce sepsis. The results demonstrated that this approach conferred potent protection against sepsis-induced ALI, as evidenced by a significant reduction in pathological scores, epithelial cell apoptosis, pulmonary edema, vascular permeability, and the expression of inflammatory cytokines and neutrophil infiltration in the lung tissues of septic mice. In addition, RNA interference of Btk significantly suppressed p-38 and iNOS signaling pathways in transduced alveolar macrophages in vitro. These results identify a novel role for BTK in lethal sepsis and provide a potential new therapeutic approach to sepsis and ALI.
脓毒症是外科患者常见且严重的并发症，常导致多器官功能衰竭综合征（MOFS），包括急性肺损伤（ALI）和急性呼吸窘迫综合征（ARDS）。尽管采取了强化支持治疗和多种治疗方式，但这些患者的死亡率仍然很高。在本研究中，我们调查了胞质酪氨酸激酶Btk/Tec家族成员伯顿酪氨酸激酶（BTK）在脓毒症发病机制中的作用，并在盲肠结扎和穿刺（CLP）诱导的脓毒症小鼠模型中评估了体内Btk RNA干扰的保护作用。经气管内注射Btk siRNA后，对小鼠进行CLP以诱导脓毒症。结果表明，这种方法对脓毒症诱导的ALI具有强大的保护作用，脓毒症小鼠肺组织的病理评分、上皮细胞凋亡、肺水肿、血管通透性以及炎性细胞因子表达和中性粒细胞浸润显著降低证明了这一点。此外，Btk的RNA干扰在体外显著抑制了转导的肺泡巨噬细胞中的p-38和iNOS信号通路。这些结果确定了BTK在致死性脓毒症中的新作用，并为脓毒症和ALI提供了一种潜在的新治疗方法。
