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目的:观察阿霉素(DOX)诱导猪肝脏热休克蛋白72(以下简称HSP72)蛋白表达在腹腔内区域性血流阻断动脉内化疗(以下简称stopflow)过程中对肝脏的保护作用,并探讨其保护机制。方法:将12只健康杂交雌性幼猪随机分为两组,DOX组动物施行stopflow式介入化疗,术前24h以每公斤体重1mg经外周静脉注射DOX;NS组则注射生理盐水。分别检测肝脏组织中HSP72及NFκBp65亚基表达。检测外周血ALT及AST水平,肝脏活检进行组织形态学观察,以评价阻断前及阻断区域血循环再通后不同时间段中的肝脏损伤程度。结果:注射DOX后24h,可见肝脏HSP72蛋白呈强阳性表达,NS组肝脏NFκBp65表达阳性,且逐渐减弱;而DOX组动物肝脏组织NFκBp65呈阴性,血清ALT、AST水平低于NS组(P<0.05),组织形态学改变亦轻于NS组。结论:术前应用DOX可诱导肝脏HSP72蛋白表达,并通过抑制NFκB激活而减轻stopflow过程对肝脏的影响。
Objective: To observe the protective effect of doxorubicin (DOX) on liver heat shock protein 72 (hereinafter referred to as HSP72) in the liver during intraperitoneal regional blood flow blocking intra-arterial chemotherapy (hereinafter referred to as stopflow) Its protection mechanism. Methods: Twelve healthy female piglets were randomly divided into two groups. Animals in DOX group received stopflow interventional chemotherapy. DOX was injected intravenously 1mg per kilogram of body weight at 24 hours before surgery in rats. Normal saline was injected into NS group. The expression of HSP72 and NFκBp65 subunit in liver tissue were detected respectively. Peripheral blood ALT and AST levels were detected, and liver biopsy was performed to observe the histological changes to evaluate the degree of hepatic injury at different time points after blood circulation recanalization. Results: 24h after injection of DOX, the expression of HSP72 protein in the liver was strongly positive. The expression of NFκBp65 in the liver of NS group was positive and gradually decreased. However, the level of NFκBp65 in the liver of DOX group was lower than that of the NS group (P <0.05) ), Histological changes were also lighter than the NS group. Conclusion: Preoperative application of DOX can induce liver HSP72 protein expression and reduce the effect of stopflow on liver by inhibiting NFκB activation.