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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 investigate the effect of pyrrolidine carbodithioic acid (PDTC) on the expression of ET-1, VEGF and TNF-α in the portal vein and its surrounding tissues in hepatic portal vein sponge-like rats after inhibiting NF-κB activity . Methods Eighty male Sprague-Dawley rats were randomly divided into control group, sham operation group, cavernous degeneration group of hepatic portal vein and inhibitor of NF-κB (PDTC group). The latter two groups were treated with cavernous degeneration of hepatic portal vein. The control group, the sham operation group and the cavernous degeneration group of hepatic portal vein were injected subcutaneously with 0.2% 0.9% NaCl solution every day. The PDTC group was subcutaneously injected with PDTC solution (100 mg / kg) for 4 weeks. The portal vein pressure, the contents of ET-1, VEGF, TNF-α in the portal vein and its surrounding tissues and the content of NF-κB p65 in the nucleus were detected after 2 weeks of withdrawal. Results After partial hepatic portal vein ligation for 6 weeks, typical portal vein cavernous degeneration and elevated portal pressure were found. The contents of ET-1, VEGF, TNF-α and activated NF-κB p65 in the tissue were significantly lower than those in the control group The operation group showed an upward trend with a significant difference (P <0.01). The levels of ET-1, VEGF, TNF-α and NF-κB p65 in portal vein pressure and tissue were decreased compared with those in hepatic portal vein sponge-like degeneration group with NF-κB inhibitor intervention (P <0.01), but there is still an upward trend compared with the control group and the sham operation group (P <0.01). NF-κB, ET-1, TNF-α and VEGF are involved in the pathophysiological process of CTPV.2. PDTC can decrease the expression of VEGF, TNF-αand ET-1 by inhibiting the NF- Inhibit the formation of cavernous degeneration of hepatic portal vein and relieve portal hypertension.