肠外营养导致大鼠肝细胞周期基因的变化及临床意义

目的 本研究利用实时定量PCR芯片技术,检测TPN后肝脏细胞周期基因表达的变化,探讨哪些基因在肝脏损害中发挥作用,为临床预防和治疗PNALD提供资料.方法 选择12只雄性SD大鼠,随机分为TPN组(6只)和生理盐水对照组(6只),7d后应用实时定量PCR芯片检测方法 ,比较两组大鼠间肝脏细胞周期基因的表达.结果 TPN组大鼠肝脏病理表现为肝细胞弥漫的脂肪空泡变性,小叶中央区较周边区更为明显;TPN组大鼠肝脏细胞周期表达上调基因有Atm、Brea1、CAkn1b、Dnajc2、G2a、Nfatc1、Notch2、Pkd1、Ppp2r3a等,表达下调基因有CAc25b、Ccnd1、E2f1、Mcm3、Nek2、Wee1等.结论 TPN组与生理盐水对照组大鼠比较,肝脏细胞周期基因表达存在差异,肝细胞周期基因ATM、BRCA1、Cdkn1b 等表达的改变,提示肝细胞增生减少和凋亡的增加,从而阻止肝细胞的修复,可能TPN与肝脏损伤的发生和发展相关.

Parenteral nutrition leads to alteration of hepatocyte cell cycle? Gone expression in rats

Objective Total parenteral nutrition (TPN)-associated liver disease (PNALD) is a well-recognized complication. Despite the severity of this disease, neither the etiology nor the patho-physiology of PNALD is currently understood. The goal of these experiments was to determine changes of cell cycle genes, using real time PCR array. Methods 12 male SD rats were randomized into two groups. The TPN group (N=6) received standard TPN solution through a silastic catheter inserted in the right jugular vein and similarly the control group (N = 6) received the physiologic saline. After 7 days of infusion,we analyze the difference of cell cycle gene expressions between the two groups with real time PCR array. Results The TPN group was found to have large lipid droplets with unclear mar-gins in the perilobular region and smaller lipid droplets in the centrilobular regions. Nine genes were up-regulated in the TPN group: Atm, Brca1, Cdkn1b, Dnajc2, G2a , Nfatc1, Notch2, Pkd1, Ppp2r3a. Seven genes with down-regulated in the TPN group: Cdc25 b, Cend 1, E2f 1, Mcm3, Mcm2, Nek2, Wee1. Conclusions This study demonstrates significant ahemations in gene expressions in liver of rats which received TPN. These alterations may provide insight into potential mechanism of TPN-induced hepato-cyte injury.