摘要自身免疫性肝炎是由异常的免疫反应引起的肝损伤，目前的治疗主要采用免 疫抑制剂，副作用较大，寻找安全有效的治疗药物已成为迫切需要。刀豆蛋白A 诱导的小鼠肝损伤与人类自身免疫性肝炎的发病机制和表型非常相似，因此被广 泛用于自身免疫性肝炎的药物筛选。在本实验中，我们拟研究一种新型的β-葡聚 糖索拉胶对刀豆蛋白A诱导的小鼠肝损伤是否具有保护作用，并对机制进行初步 探讨。将C57BL/6小鼠用索拉胶预处理，再尾静脉注射刀豆蛋白A。研究结果发现 索拉胶可以减轻刀豆蛋白A导致的肝损伤，降低肝脏中炎性细胞因子IL-6、IL-1β 的表达。索拉胶发挥保护作用并不是通过抑制自噬和凋亡发生的，其作用机制可 能是抑制刀豆蛋白A诱导的T细胞和B细胞向肝脏浸润，进而减轻肝脏损伤。 研究结果为索拉胶作为自身免疫性肝炎治疗药物的开发提供实验基础。73306

毕业论文关键词 索拉胶 刀豆蛋白 A 肝损伤

Salecan attenuates concanavalin A-induced liver 

Abstract

Autoimmune hepatitis (AIH) is characterized by abnormal immune responses against the liver。 Currently, AIH is usually treated with immunosuppression, which, cause many side effects。 Thus, safe and effective pharmacological treatments are urgently needed。 Concanavalin A (ConA)-induced hepatitis in mice is a well-developed model of immune-mediated liver injury, which closely mimics the pathogenesis mechanisms and pathological changes of AIH in human, and has been widely used in the drug development for AIH。 The aims of the present study were to investigate the protective effect of salecan against ConA-induced liver injury, and to clarify the related mechanisms。 C57BL/6 mice were pretreated with salecan followed by ConA injection。 Salecan treatment significantly reduced ConA-induced liver injury, and decreased the expression of inflammatory cytokines including interleukin (IL)-6 and IL-1β in ConA-treated mice。 The protective effect of salecan was not due to its inhibition of autophagy and apoptosis, but through the inhibition of T cell and B cell- infiltration into the liver after ConA-treatment。 The result suggested the  therapeutic potential of salecan  in    immune-mediated hepatitis。

目 录

引言 1

1。1 研究背景 1

1。2 肝损伤模型的建立 1

1。 3 Con A 诱导的肝损伤的发病机制 2

1。 4 ConA 诱导的肝损伤保护及药物筛选研究 2

1。4。1 虾青素对 ConA 诱导的自身免疫性肝炎的保护作用 2

1。4。2 高良姜素（Galangin）对 ConA 诱导小鼠肝炎的保护作用 3

1。4。3 当归多糖能削弱刀豆蛋白 A 诱导的小鼠肝损伤 3

1。4。4 β-葡聚糖在免疫调节及肝损伤保护中的作用 4

1。 5 实验研究的主要内容和意义 5

实验材料与方法 6

2。1