Hepatic preconditioning of doxorubicin in stop-flow chemotherapy:NF-κB/IκB-α pathway and expression

来源 :World Journal of Gastroenterology | 被引量 : 0次 | 上传用户:thinkthinkthink
下载到本地 , 更方便阅读
声明 : 本文档内容版权归属内容提供方 , 如果您对本文有版权争议 , 可与客服联系进行内容授权或下架
论文部分内容阅读
AIM: To provide hepatic protection through administration of doxorubicin before stop-flow chemotherapy (SFC) and to investigate the expression of heat shock protein 72 (HSP72) and role of nuclear factor kappa B (NF-κB) in this effect. METHODS: The hepatic preconditioning of doxorubicin was established in a porcine model by injection of doxorubicin (1 mg/kg) before SFC. The experimental animals were randomized into two groups: groups receiving doxorubicin (DOX) and normal saline (NS). Serial serum and tissue samples were taken from both groups to evaluate the protection of doxorubicin. Western blot and immunoprecipitation were applied to detect the expression of HSP72, NF-κB p65 protein, inhibitor κB-α (IκB-α) and phosphorylated IκB-α as well. The expression of tumor necrosis factor α (TNF-α) was estimated by semiquantitative RT-PCR. And the extent of the hepatic injury was estimated with the level of serum aminotransferases. RESULTS: An abundance production of HSP72 in porcine liver was observed after 24 h of intravenous administration of doxorubicin, but without any change in the expression of NF-κB p65 subunit in cytoplasm. NF-κB p65 subunit accumulated in nuclei at the end of SFC and reached its highest level at 30 min after the restoration of the abdominal circulation and decreased gradually during the 6 h after SFC in NS group, while there was little change in DOX group. There was also a slight decrease of IκB-α at 30 min after the restoration of the abdominal circulation in NS group accompanying with the appearance of phosphorylated IκB-α. The expression of TNF-α was significantly higher in NS group than that in DOX group (average 1.40±0.17 vs 0.62±0.22, P<0.01) at serial time points after SFC. Serum ALT and AST levels of NS group were higher after 24 h than those of DOX group (93.2±7.8 IU/L vs 53.3±13.9 IU/L, 217.0±29.4 IU/L vs 155.0±15.6 IU/L for ALT and AST respectively, P<0.05) and after 48 h than those of DOX group (66.6±18.1 IU/L vs 43.3±16.7 IU/L, 174.4±21.3 IU/L vs 125.7±10.5 IU/L for ALT and AST respectively, P<0.05). CONCLUSION: Doxorubicin renders the liver to be tolerant to the hepatic influence in SFC in a porcine model through the NF-κB/IκB-αpathway with the expression of HSP72. AIM: To provide hepatic protection through administration of doxorubicin before stop-flow chemotherapy (SFC) and to investigate the expression of heat shock protein 72 (HSP72) and role of nuclear factor kappa B (NF-κB) in this effect. METHODS: The hepatic preconditioning of doxorubicin was established in a porcine model by injection of doxorubicin (1 mg / kg) before SFC. The experimental animals were randomized into two groups: groups receiving doxorubicin (DOX) and normal saline (NS). Serial serum and tissue samples were taken from both groups to evaluate the protection of doxorubicin. Western blot and immunoprecipitation were applied to detect the expression of HSP72, NF-κB p65 protein, inhibitor κB-α (IκB-α) and phosphorylated IκB-α as well. of tumor necrosis factor α (TNF-α) was estimated by semiquantitative RT-PCR. And the extent of the hepatic injury was estimated with the level of serum aminotransferases. RESULTS: An abundance production of HSP72 in porcin e liver was observed after 24 h of intravenous administration of doxorubicin, but without any change in the expression of NF-κB p65 subunit in cytoplasm. NF-κB p65 subunit accumulated in nuclei at the end of SFC and reached its highest level at 30 min after the restoration of the abdominal circulation and the gradually progressive after 6 h after SFC in NS group, while there was little change in DOX group. There was also a slight decrease of IκB-α at 30 min after the restoration of the abdominal circulation in NS group accompanying the appearance of phosphorylated IκB-α. The expression of TNF-α was significantly higher in NS group than that in DOX group (average 1.40 ± 0.17 vs 0.62 ± 0.22, P <0.01) at serial time points after SFC. Serum ALT and AST levels of NS group were higher after 24 h than those of DOX group (93.2 ± 7.8 IU / L vs 53.3 ± 13.9 IU / L, 217.0 ± 29.4 IU / L vs 155.0 ± 15.6 IU / L for ALT and AST respectively, P <0.05) and after 48 h of those DOX groups (66.6 ± 18.1 IU / L vs 43.3 ± 16.7 IU / L, 174.4± 21.3 IU / L vs. 125.7 ± 10.5 IU / L for ALT and AST respectively, P <0.05). CONCLUSION: Doxorubicin renders the liver to be tolerant to the hepatic influence in SFC in a porcine model through the NF-κB / IκB- αpathway with the expression of HSP72.
其他文献
Patients with mechanical obstruction of the pancreatic duct, which can be cau sed by chronic pancreatitis, suffer from recurrent attacks of pain and inflammat i
上一期我们了解了不少关于大脑的秘密,这一期,我们将通过更多的实验来认识大脑。当然啦,弗朗肯斯坦男爵和怪物男孩还会继续参加。瞧,这会儿他们正在跳舞,据说是为了一个关于
Objective. To evaluate the occurrence and changes over time of upper gastroint estinal symptoms in adult subjects randomly recruited from the general populatio
<正>The Inaugural Ceremony of National Technical Committee of Standardization for Mobile Laboratories and 1~(st) Working Conference was successfully held in She
Objective. Endoscopy is the gold standard for diagnostic evaluation of upper gastrointestinal symptoms. The relation between endoscopy and use of antisecretory
这本书讲了一个什么故事  英国伦敦的孤儿院中,一个八岁的女孩索菲在失眠之夜目睹了一个提着包和旧喇叭的巨人走在街上。她惊慌失措,正想躲起来,却被巨人从窗口抓走了。巨人将她带到一个遥远的山洞里,却并没有吃掉她,因为他是一个好心眼儿的巨人。他常将美梦通过喇叭吹进熟睡的小朋友的脑袋里。但是,他禁止索菲回孤儿院,因为这世上的人不该知道吹梦巨人的存在。如果索菲试图逃跑,那她很可能被那些比好心眼儿巨人还高大许多
2010年国家社科基金年度项目评选结果近日揭晓,中央民族大学14项课题喜获国家社科基金立项资助。它们分别是:马克思晚年笔记整体研究(王晓红)、国际产业组织发展新趋势研究(
有关唐长安城里坊的研究,清人徐松撰著的《唐两京城坊考》,是继唐代韦述《两京新记》、宋代宋敏求《长安志》之后,记述最为详备的巨著,被誉为“集大成”之作,向为后世人们研
BACKGROUND: Somatostatin is abundant in the hypothalamus,cerebral cortex,limbic system,and mesencephalon. Somatostatin mRNA expression in the brain of rats with
一、冶金企业高技能人才建设中的主要问题1、高技能人才的成长环境不理想。一是缺氛围。社会对高技能人才的认识仍存在偏见,社会“重管理、轻技能”的观念严重影响了技能人才