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Histological alterations in the livers of Cx43-deficient mice submitted to a cholestasis model

机译:提交给胆汁淤积模型的Cx43缺陷小鼠肝脏的组织学改变

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Gap junction intercellular communication capacity and connexin expression are reportedly involved in cell proliferation. To understand the participation of connexins in biliary duct hyperplasia, a cholestasis model was applied to mice with heterologous deletion of Gja 1, the connexin 43 (Cx43) gene. Heterozygous (Cx43+/-) knockout (KO) and wild-type mice (Cx43+/+) (WT) were submitted to bile duct ligation and euthanized at different time points (48 h, 7 days, and 14 days) after surgery. After euthanasia, the macroscopic and microscopic liver alterations were examined. A histomorphometric study of the livers was performed. For this purpose, a grid containing 100 points was applied to each liver section. The volumetric fraction of bile ducts, hepatocytes, arterioles, and terminal hepatic vein were quantified. Cell proliferation was also quantified by western blot PCNA. High mortality was observed in both genotypes. The heterologous deletion of Cx43 did not affect the biliary duct hyperplasia or most of the other parameters analyzed; however, the Cx43-deficient mice showed decrease in hepatic vein angiogenesis in comparison with the wild-type mice 48 h after surgery. In conclusion, our results indicate that the Cx43 gene heterologous deletion does not affect the biliary duct hyperplasia; on the other hand, connexin 43 deficiencies do affect the hepatic vein angiogenesis, although other studies to understand the details of this influence will be necessary. (c) 2007 Elsevier Inc. All rights reserved.
机译:据报道,间隙连接的细胞间通讯能力和连接蛋白表达与细胞增殖有关。为了了解连接蛋白在胆管增生中的参与,将胆汁淤积模型应用于异源缺失Gja 1(连接蛋白43(Cx43)基因)的小鼠。将杂合子(Cx43 +/-)敲除(KO)和野生型小鼠(Cx43 + / +)(WT)进行胆管结扎,并在手术后的不同时间点(48 h,7天和14天)安乐死。安乐死后,检查宏观和微观肝脏改变。进行了肝脏的组织形态学研究。为此,将包含100个点的网格应用于每个肝脏切片。定量胆管,肝细胞,小动脉和终末肝静脉的体积分数。细胞增殖也通过蛋白质印迹PCNA来定量。两种基因型均观察到高死亡率。 Cx43的异源删除不影响胆管增生或所分析的大多数其他参数。然而,与野生型小鼠相比,Cx43缺陷型小鼠术后48小时肝静脉血管生成减少。总之,我们的结果表明Cx43基因异源缺失不影响胆管增生。另一方面,连接蛋白43的缺乏确实会影响肝静脉血管生成,尽管有必要进行其他研究以了解这种影响的细节。 (c)2007 Elsevier Inc.保留所有权利。

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