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目的探讨NF-κB在大鼠肝缺血再灌注损伤与缺血预处理(IPC)保护机制中的作用。方法将72只SD雄性大鼠随机分成4组:缺血再灌注损伤组(I/R组);缺血预处理组(IPC组);NF抑制剂组(应用二硫代氨基甲酸吡咯烷即PDTC组);假手术组(S组)。测定血清丙氨酸氨基转移酶(ALT),天冬氨酸氨基转移酶(AST),乳酸脱氢酶(LDH)活性;测定肝脏的湿干比(W/D);经HE切片染色后,观察肝组织显微结构;分别应用免疫组化和Western blot免疫印迹法测定肝组织中的TNF-α和NF-κB表达。结果 I/R组大鼠血清肝酶学指标(AST、ALT、LDH)和肝脏的组织形态学都显示较S组大鼠有明显的肝脏损伤。同时肝组织W/D比值和TNF-α的阳性表达比及NF-κB在免疫组化和western blot免疫印迹中的表达亦均明显高于S组(P<0.01)。IPC组和PDTC组大鼠肝损伤程度明显轻于I/R组,同时TNF-α和NF-κB在两种检测方法中的表达亦均明显低于I/R组(P<0.05)。结论 NF-κB在肝I/R损伤的发生机制中是细胞信号传导通路上的重要转录因子,对I/R损伤的炎症反应起介导作用;NF-κB的活化被抑制是肝IPC保护机制中的重要环节;针对NF-κB的靶向治疗是临床肝保护有意义的新途径。
Objective To investigate the role of NF-κB in the protective mechanism of hepatic ischemia-reperfusion injury and ischemic preconditioning (IPC) in rats. Methods Seventy-two SD male rats were randomly divided into 4 groups: ischemia / reperfusion injury group (I / R group), ischemic preconditioning group (IPC group), NF inhibitor group (pyrrolidine dithiocarbamate PDTC group); sham operation group (S group). Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) activity were measured. The wet / dry ratio (W / D) of the liver was measured. The microstructure of liver tissue was observed. The expression of TNF-α and NF-κB in liver tissue were detected by immunohistochemistry and Western blot respectively. Results Serum liver enzymological indexes (AST, ALT, LDH) and liver histomorphology of I / R rats showed obvious hepatic injury compared with that of S rats. Meanwhile, the expression of W / D ratio and TNF-α in liver tissue and the expression of NF-κB in immunohistochemistry and western blot were also significantly higher than those in group S (P <0.01). The levels of liver injury in IPC group and PDTC group were significantly lower than those in I / R group. The expressions of TNF-α and NF-κB in both groups were significantly lower than those in I / R group (P <0.05). Conclusion NF-κB is an important transcription factor in cell signal transduction pathway in the mechanism of hepatic I / R injury and plays a mediating role in the inflammatory response to I / R injury. The inhibition of NF-κB activation is a mechanism of liver IPC protection In the important part; targeted therapy for NF-κB is a new way of clinical liver protection meaningful.