局部血管紧张素Ⅱ水平与核因子-κB、p38丝裂素活化蛋白激酶信号传导通路活化在人门静脉高压症脾静脉血管病变中的作用

目的 探讨血管紧张素Ⅱ(AngII)与核因子(NF)-κB、p38丝裂素活化蛋白激酶(p38MAPK)信号传导通路活化在人门静脉高压症(PHT)脾静脉血管病变中的作用及其机制.方法 PHT组为乙肝后肝硬化门静脉高压症患者26例;对照组选取因外伤性脾破裂行脾切除术患者10例.放免法(RIA)检测脾静脉中AngII水平;免疫组织化学法测定脾静脉中NF-κB、Phospho-p38蛋白的表达.蛋白免疫印迹法检测脾静脉及体外培养的脾静脉血管平滑肌细胞的NF-κB 、Phospho-p38蛋白的表达.结果 PHT组脾静脉组织AngII为(248.91±48.31)ng/L,显著高于对照组AngII为(143.35±36.45)ng/L(P<0.01).免疫组织化学和蛋白免疫印迹均显示PHT组脾静脉NF-κB 、Phospho-p38蛋白的表达较对照组明显增强.体外培养脾静脉血管平滑肌细胞(VSMC),AngII在1×10-8～1×10-6mol/L浓度范围内,AngII以浓度依赖性方式增加人脾静脉VSMC中NF-κB 、Phospho-p38蛋白的表达.结论 门静脉高压症时脾静脉组织AngII水平升高,NF-κB、Phospho-p38蛋白表达增加.AngII能激活脾静脉血管平滑肌细胞NF-κB、p38信号传导通路.门静脉高压症时AngII可能通过激活P38和NF-κB信号对传导通路门静脉高压症的形成和维持可能起重要作用.

The levels of local angiotensin II (AngII) and activation of p38 mitogen-activated protein kinase and NF-kB signaling pathways in splenic vein vasculopathy of portal hypertension

Objective To investigate the levels of local angiotensin II (AngII) and activation of p38MAPK and NF-kB signaling pathways in human splenic vein vasculopathy of portal hypertension (PHT) and discuss the possible action mechanism.Methods Twenty-six patients with posthepatitic cirrhosis PHT admitted to the first affiliated Hospital of Fujian Medical University served as PHT group,and 10 patients with traumatic spleen rupture during the same period as the control group.RIA method was used to determine local AngII level in splenic veins.The expression of NF-κB and Phospho-p38 in humansplenic veins was assayed by immunohistochemistry and Western blot.Vascular smooth muscle cells (VSMCs) were obtained from human splenic vein of PHT.The expression of NF-κB and Phospho-p38 in human splenic veins and VSMC of splenic veins was detected by Western blot.Results The levels of local AngII in the splenic veins of PHT group were (248.91±48.31) ng/L,significantly higher than those in the control group (143.35±36.45) ng/L] (P<0.01).The expression of NF-κB and Phospho-p38 in the splenic vein of PHT group was stronger than in control group (P<0.01).Within a certain concentration coverage,AngII (1×10-8-1×10-6 mol/L) increased the expression of NF-κB and Phospho-p38 in VSMC of splenic veins in a dose-dependent manner.Conclusion During PHT,in splenic vein the level of AngII was enhanced and the expression of NF-kB and phospho-p38 increased.AngII could activate the NF-κB and p38MAPK signaling pathways in the VSMCs of splenic vein.AngII may be critical for the formation and maintenance of PHT.