Shabat Yehudit, Ya'acov Ami Ben, Ilan Yaron
Gastroenterology and Liver Units, Department of Medicine, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
J Clin Transl Hepatol. 2018 Dec 28;6(4):345-349. doi: 10.14218/JCTH.2018.00030. Epub 2018 Nov 5.
The serine proteinase inhibitor alpha-1 anti-trypsin (AAT) protects the body against protease activity. Several functions of AAT beyond those attributed to its anti-protease activity have been described, among them immunomodulatory and anti-inflammatory properties. The present study aimed to determine the efficacy of AAT for the treatment of immune-mediated liver injury using the models of concanavalin A-induced immune-mediated hepatitis and acetaminophen -induced liver damage. AAT was administered to mice subjected to concanavalin A-induced immune-mediated hepatitis or 2 h after acetaminophen-induced liver damage. Mice were followed for changes in serum levels of liver enzymes, liver histology, and for interferon gamma serum levels. Treatment with AAT alleviated concanavalin A-induced immune-mediated liver damage, as demonstrated by a reduction in the serum levels of liver enzymes and interferon gamma, and an improved lymphocyte infiltration into the liver on liver biopsies. Moreover, treatment with AAT was associated with alleviation of the acetaminophen-induced liver injury. AAT exerts an hepatoprotective effect on immune-mediated and drug-induced liver damage. The data support its potential use in patients with immune-associated liver disorders.
丝氨酸蛋白酶抑制剂α-1抗胰蛋白酶（AAT）可保护机体免受蛋白酶活性的影响。除了其抗蛋白酶活性外，AAT的几种功能也已被描述，其中包括免疫调节和抗炎特性。本研究旨在使用伴刀豆球蛋白A诱导的免疫介导性肝炎模型和对乙酰氨基酚诱导的肝损伤模型，确定AAT治疗免疫介导性肝损伤的疗效。将AAT给予遭受伴刀豆球蛋白A诱导的免疫介导性肝炎的小鼠，或在对乙酰氨基酚诱导的肝损伤2小时后给药。观察小鼠肝酶血清水平、肝脏组织学以及干扰素γ血清水平的变化。AAT治疗减轻了伴刀豆球蛋白A诱导的免疫介导性肝损伤，这表现为肝酶和干扰素γ血清水平降低，以及肝脏活检时肝脏淋巴细胞浸润改善。此外，AAT治疗与减轻对乙酰氨基酚诱导的肝损伤有关。AAT对免疫介导性和药物性肝损伤具有肝保护作用。这些数据支持其在免疫相关性肝脏疾病患者中的潜在应用。
