Screening for Protective Effect Target of Deproteinized Extract of Calf Blood and Its Mechanisms in Mice with CCl4-Induced Acute Liver Injury

Liver injury is the common pathological basis of various liver diseases, and its existence for a long time is often a important initiation factor to lead to liver fibrosis, and even liver cirrhosis and hepatocellular carcinoma (HCC), so that the prevention and treatment of liver injury is one of the key links in the clinical therapy of liver diseases, and the timely control of the occurrence and development of liver injury will have an important clinical significance in the treatment of liver disorders. It has been reported that deproteinized extract of calf blood (DECB) can inhibit the replication of hepatitis B virus and has a protective effect on the liver function after a traumatic liver injury. However, there are few studies on the regulatory factors and mechanisms of DECB effects. In this study, an acute mouse liver injury model was established with carbon tetrachloride (CCl4), mRNA expression microarray was used to screen the differentially expressed genes and related pathways in mice in the DECB group and model group, and the target of protective effect of DECB and its related mechanism were found in mice with acute liver injury induced by carbon tetrachloride, which may provide an important theoretical basis for the further research and development of DECB. After they were acclimated to the laboratory environment for 3d, 20 male mice were randomly divided into 2 groups: model group (M), DECB group, 10 mice in each group.The DECB group was given DECB (1g/kg), and those in the M group (20 BW) were given normal saline (20mL/kg) intragastrically once daily continuously for 30d. At two hours after the last administration, mice in M and DECB groups were injected with 10% carbon tetrachloride blend oil (10mL/kg).

肝损伤是各类肝脏疾病的常见病理基础，其长期存在往往是引发肝纤维化甚至肝硬化、肝细胞癌（hepatocellular carcinoma, HCC）的重要启动因素。因此，肝损伤的防治是肝脏疾病临床治疗的关键环节之一，及时遏制肝损伤的发生与发展对肝脏疾病的诊疗具有重要临床意义。

已有研究表明，去蛋白小牛血提取物（deproteinized extract of calf blood, DECB）可抑制乙型肝炎病毒复制，并对创伤性肝损伤后的肝功能具有保护作用，但目前关于DECB发挥作用的调控因子与机制的研究尚少。本研究采用四氯化碳（carbon tetrachloride, CCl4）构建急性小鼠肝损伤模型，通过mRNA表达微阵列（mRNA expression microarray）筛选DECB组与模型组小鼠的差异表达基因及相关通路，阐明DECB对四氯化碳诱导的急性肝损伤小鼠的保护作用靶点及其相关机制，可为DECB的后续研发提供重要理论依据。

实验动物经3天实验室环境适应后，将20只雄性小鼠随机分为2组：模型组（M组）与DECB组，每组10只。DECB组每日灌胃给予DECB（1g/kg体重），模型组给予生理盐水（20mL/kg体重），每日一次，连续灌胃30天。末次给药2小时后，模型组与DECB组小鼠均注射10%四氯化碳混合油溶液（10mL/kg体重）。