核因子-кB的活化与基质Gla蛋白mRNA的表达在门静脉高压症血管病变中的意义

Activation of nuclear factor-кB and expression of matrix Gla protein mRNA in vasculopathy of portal hypertension

目的探讨脾脏动、静脉组织内核因子-kappaB(NF-кB)的活化与基质Gla蛋白(ma- trix Gla protein,MGP)mRNA的表达在门静脉高压症性血管病变中的意义。方法实验组为肝炎后肝硬化门静脉高压症(portal hypertension,PHT)患者28例,住院期间行择期脾切除加贲门周围血管离断术;对照组选取同期因外伤性脾破裂急诊入院行脾切除术患者12例。采用化学发光凝胶电泳迁移率(electrophoretic mobility shift assay,EMSA)方法检测脾脏动、静脉血管NF-кB的活性;采用逆转录-聚合酶链反应(RT-PCR)方法检测血管组织的MGPmRNA表达。结果对照组内脾脏动、静脉组织MGPmRNA分别为0.23±0.10、0.26±0.13,显著低于PHT组脾动脉、脾静脉的0.58±0.19、0.55±0.15,差异有统计学意义(P<0.05);于PHT组脾动、静脉内检测到NF-кB活性表达1.44±0.23、1.38±0.18,显著高于对照组脾动、静脉的0.19±0.12、0.25±0.16,差异有统计学意义(P<0.05),且PHT组脾脏动、静脉MGP mRNA表达与NF-кB的活性呈显著正相关(r=0.692,P<0.05;r=0.703,JP<0.05)。结论肝硬化时PHT血管组织内NF-кB的活化,MGP mRNA的表达增强,调节血管平滑肌细胞(vascular smooth muscle cell,VSMC)的增殖和迁移,并参与了内脏血管病变形成和发展。

Objective To investigate the activation of nuclear factor-κB （NF-κB） and expression of matrix Gla protein （MGP） mRNA in splenic artery and vein of PHT patients and its role in the pathogenesis of portal hypertensive vasculopathy. Methods Twenty - eight patients with posthepatitic cirrhosis portal hypertension （20 males and 8 females） admitted to Tongji Hospital were subjected to splenectomy .plus pericardial devascularization during hospitalization （experimental group） ,while 12 patients （8 males and 4 females） with traumatic spleen rupture subject to splenectomy during the same period as the control group. Chemiluminescent electrophoretic mobility shift assay （EMSA） was used to detect the activity of NF-κB in splenic artery and vein, and the expression of MGP mRNA in splenic artery and vein of PHT patients and normal vascular was assayed by RT-PCR. Result The expression of MGP mRNA in splenic artery and vein of PHT group was 0.58 ±0. 19 and 0.55 ±0. 15 respectively, significantly higher than in control group （0.23 ±0.10 and 0.26±0.13 ,P 〈0.05）. The activity of NF-κB in splenic artery and vein of PHT patients was significantly higher than in control group （ P 〈 0.05 ） , and the expression of MGP mRNA in splenic artery and vein of PHT patients had a significant positive correlation with the activity of NF-κB （r=0. 692,P 〈0. 05;r=0. 703,P 〈0. 05,respectively）. Conclusion Activation of NF-κB and significant expression of MGP mRNA in splenic artery and vein of PHT can regulate proliferation and migration of vascular smooth muscle cells （VSMC）, and also take part in the development of portal hypertensive vaseulopathy.