肝病动物模型(DDC造模饲料):DDC主要引起胆道损伤,也会导致门静脉周围肝细胞损伤,该模型被描述为PBC和 PSC 的小鼠模型。造模饲料参考:添加含0.1%DDC的模型饲料。
肝纤维化动物模型改良饲料法
通过饲喂改良后的饲料或添加剂,也可以诱导小鼠引起胆汁淤积肝脏损伤模型。5-二乙氧基羰基-1,4-二氢二氢吡啶 (DDC) 和 α-萘异硫氰酸盐(ANIT)。每日给予小鼠含 0.1%DDC饲料,1 周后在胆管上皮细胞中可见血管细胞黏附的表达分子、骨桥蛋白和肿瘤坏死因子-α 上调。持续8 周导致胆卟啉增多,胆管周围肌成纤维细胞活化,引起胆道纤维化与人类硬化性胆管炎相似。每日给予小鼠 0.025% ANIT,饲喂数天后,就可引起胆汁淤积性损伤,引起胆管上皮细胞损伤,胆管上皮扩张,轻度肝细胞损伤和门静脉周围炎症导致肝纤维化。2 化学性损伤诱导致肝纤维化化学性肝纤维化是由能造成肝毒性的化学物质所引起的肝细胞损伤和修复交替出现导致肝内结缔组织异常增生的直接结果。造模所使用的常用药物试剂为四氯化碳(CCl4)、二甲基亚硝胺(DMN)等物质,这类物质具有强烈的肝损害性,能够在不同程度破坏肝脏细胞导致肝内结缔组织异常增生。
肝纤维化动物模型CCl4
四氯化碳(CCl4)是一种无色有机溶剂,对任何油脂具有很强的溶解性,尤其是动物油脂,因此,在人体表现为强肝毒性。CCl4法是用于复制肝脏损伤模型的常用方法。CCL4模型复制方法成熟,成功率高达 89.33%,简单易行、经济安quan。一般从第 2 周开始,就可出现不同程度肝纤维化程度,平均 4.9%,至第 8 周可达到平均 9.2% 的纤维化,能很好地模拟人类肝纤维化 S0~S4 期的病理特征,且与乙肝病毒感染所致肝纤维化的病理特征相似。该方法现已广泛应用于研究鼠类肝纤维化发生机制、筛选血清标志物以及开发抗纤维化药物等。但该方法由于 CCl4处理后的肝毒性剧烈,死亡率较高。总体来说,该方法在某种程度上基本可以满足实验需求,同时也需要改进来弥补缺点。
论文信息:
论文题目: HMGB1 links chronic liver injury to progenitor responses and hepatocarcinogenesis
期刊名称:J Clin Invest.
时间期卷:2018;128(6):2436-2450.
在线时间:2018年3月20日
DOI:doi.org/10.1172/JCI91786.
产品信息:
货号:CP-005-005
规格:5ml+5ml
品牌:Liposoma
产地:荷兰
名称:Clodronate Liposomes and Control Liposomes
办事处:Target Technology(靶点科技)
Chronic liver injury models. Chronic liver injury was induced in 8- to 10-week-old male mice by feeding them a 0.1% DDC diet or an MCD diet supplemented with 0.15% ethionine for 3 weeks and 2 weeks, respectively. For selective deletion of HMGB1 in hepatocytes, Hmgb1fl/fl mice were injected i.v. with 1011 genome copies of AAV8-TBG-Cre or AAV8-TBG-LacZ on day 15 postpartum (for the Mdr2KO mice) or 6 weeks postpartum (for all other mice). For some experiments, mice fed a DDC diet were treated with ethyl pyruvate (40 mg/kg, i.p., given twice weekly throughout the entire time mice were fed DDC diet). For some experiments, mice fed a DDC diet were treated with liposomal clodronate or control liposomes (4 μl/g body weight, i.p., both from Liposoma), on days 4, 8, and 12 after starting the diet.
DDC模型氯膦酸盐脂质体清除巨噬细胞解决方案
注射方式:腹腔注射(i.p.)
注射剂量:days 4, 8, and 12
注射方案:Clo:Clodronate Liposomes的缩写
Liposoma氯膦酸盐脂质体巨噬细胞清除剂Clodronate Liposomes清除效果检测:
A. Macrophages were ablated in DDC diet treated mice by intraperitoneal injection of liposomal clodronate (n=7 mice) or control liposomes (n=11 mice) as depicted.
B. Macrophages were efficiently ablated by liposomal clodronate as demonstrated by F4/80 immunohistochemistry and qPCR for Emr1 mRNA (enconding F4/80).
C. Macrophage ablation by liposomal clodronate did not affect ductular reactions in DDC diet-treated mice as demonstrated by similar immunohistochemical staining for cytokeratin .