NF-κB对肝门静脉海绵样变性大鼠门静脉及其周围组织中VEGF、TNF-α、ET-1表达的影响

Role of nuclear factor-kappa B in expression of Endothelin-1,Vascular endothelial growth factor,tumor necrosis factor-alpha in portal vein and its peripheral tissues of rats with cavernous transformation of the portal vein

目的探讨使用吡咯烷二硫代氨基甲酸盐(pyrrolidine carbodithioic acid,PDTC)抑制NF-κB活性对肝门静脉海绵样变性大鼠门静脉及其周围组织中ET-1、VEGF、TNF-α表达的影响。方法 80只雄性SD大鼠分为对照组、假手术组、肝门静脉海绵样变性组、NF-κB抑制剂组(PDTC组),后两组均行肝门静脉海绵样变性造模处理。对照组、假手术组、肝门静脉海绵样变性组每天皮下注射0.9%NaCl溶液0.2 mL,PDTC组每天皮下注射PDTC水溶液(100 mg/kg)4周。停药2周后检测门静脉压力、门静脉及其周围组织ET-1、VEGF、TNF-α的含量以及组织胞核内NF-κBp65含量。结果采用部分肝门静脉结扎法6周后,可以形成典型的肝门静脉海绵样变性,门静脉压力升高,组织中ET-1、VEGF、TNF-α及活化状态的NF-κBp65含量较对照组及假手术组有上升趋势,且有统计学差异(P<0.01)。使用NF-κB抑制剂干预后,门静脉压力和组织中ET-1、VEGF、TNF-α、及活化状态的NF-κBp65含量较肝门静脉海绵样变性组有下降趋势,且有统计学差异(P<0.01),但较对照组及假手术组相比仍有上升趋势,且有统计学差异(P<0.01)。结论1.NF-κB、ET-1、TNF-α、VEGF共同参与了CTPV病理生理过程;2.PDTC可通过抑制NF-κB信号通路,进而降低VEGF、TNF-α、ET-1的表达,抑制肝门静脉海绵样变性的形成和缓解门静脉高压。

Objective： To observe and evaluate the expression of Endothelin-1（ET-1）,Vascular endothelial growth factor（VEGF）,Tumor necrosis factor-alpha（TNF-α） in portal vein and its peripheral tissues that is involved in cavernous transformation of the portal vein（CTPV） in rats after inhibition of nuclear factor κB（NF-κB） activation by pyrrolidine carbodithioic acid（PDTC）.Methods： A total of 80 Sprague-Dawley（SD） rats were randomly divided into four groups： control group,sham operation group、model group（CTPV group） and NF-κB inhibitor group（PDTC group）,the last two groups of CTPV model animals which induced in rats by partial portal vein ligation.Control group,sham operation group、CTPV group rats were given normal saline by hypodermic injection 4 weeks after operation or not,PDTC group rats were given PDTC 100 mg / kg by hypodermic injection 4 weeks after operation.The expression of ET-1,TNF-α、VEGF and content of NF-κBp65 in nucleus that in portal vein and its peripheral tissues,portal vein pressure were investigated after treatment 6 weeks.Results： Partial constriction of portal could make typical cavernous transformation animal model after 6 weeks;Compared with sham operation and control group rats,the portal vein pressure,the expression of ET-1,TNF-α,VEGF and the content of NF-κBp65 in nucleus which in portal vein and its peripheral tissues were significantly elevated in CTPV group and PDTC group rats（P 0.01）;Model making rats（PDTC group） given PDTC 4 weeks could significantly degrade the portal vein pressure,the expression of ET-1,TNF-α,VEGF and the content of NF-κBp65 in nucleus in CTPV rats’s portal vein and its peripheral tissues（P 0.01）.Conclusions： NF-κB,ET-1,TNF-α and VEGF involved in pathophysiological process of cavernous transformation of the portal vein,the mechanism may be by regulation of ET-1,TNF-α,VEGF expression;PDTC could inhibit NF-κB induced expression of ET-1,TNF-α,VEGF in CTPV rats.