血管活性物质在门肺高压症发病机制中的作用

Role of vasoactive substances in pathogenesis of portopulmonary hypertension

目的研究内皮素-1(ET-1)、一氧化氮(NO)、血栓素A2(TXA2)、前列环素(PGI2)、5羟色胺(5-HT)和转移生长因子-β1(TGF-β1)在门肺高压症(PPHTN)发病机制中的作用。方法对4例PPHTN(P组)和12例PHT患者(C组)进行病例-对照研究,另设10例胃肠道肿瘤患者作为正常对照(N组)。取股静脉、肺动脉和桡动脉血,测定ET-1、TXB2、5-HT、TGF-β1、NO和PGF1α。结果 P组和C组ET-1明显高于正常值,C组肺循环和体循环中ET-1含量约为N组的2.8倍,P组为N组的4倍,P组和C组间差异显著,其中以肺动脉中差异最明显[(270.62±9.03)pg/mL vs(191.56±40.90)pg/mL;t=3.752,P=0.002]。和N组相比,P组和C组NO[股静脉:P组=(47.49±11.05)μmol/L,C组=(58.83±39.85)μmol/L,N组=(23.07±7.64)μmol/L;肺动脉:P组=(49.99±11.79)μmol/L,C组=(59.76±43.63)μmol/L,N组=(23.33±8.02)μmol/L;桡动脉:P组=(43.56±9.99)μmol/L,C组=(56.84±36.38)μmol/L;N组=(22.30±6.90)μmol/L]和PGF1α[股静脉:P组=(439.28±174.58)pg/mL,C组=(423.29±289.63)pg/mL,N组=(83.98±11.94)pg/mL;肺动脉:P组=(428.94±145.13)pg/mL,C组=(378.43±214.31)pg/mL,N组=(76.47±11.91)pg/mL;桡动脉:P组=(384.42±158.40)pg/mL,C组=(383.65±276.62)pg/mL;N组=(78.27±10.86)pg/mL]也明显升高,差异显著(P<0.05);P组肺循环和体循环中两种物质的浓度和C组无统计学差异。C组肺循环和体循环中TXB2水平正常,和N组相比无统计学差异,P组股静脉和肺动脉血中的TXB2和N组相比差异显著,但仍在正常水平;在桡动脉中则明显高于正常(111.02±52.58)pg/mL,和N组(41.59±13.25)pg/mL及C组(67.03±24.82)pg/mL相比,存在统计学差异(P<0.05)。P组股静脉5-HT水平处于正常范围,肺动脉(135.51±6.64)ng/mL和桡动脉(115.36±10.14)ng/mL则明显高于N组[(61.36±23.81)ng/mL;(62.75±24.61)ng/mL]和[C组(52.38±15.81)ng/mL;(50.37±17.37)ng/mL],相比也有统计学差异(t=10.04,P<0.01;t=6.994,P<0.01)。TGF-β1检测结果正常,各组间无统计学差异。结论 ET-1升高和ET-1/NO比例失衡可能是引发PPHTN的重要原因之一。PGI2和TXA2不是PPHTN的始动因素,TXA2可能加重PPHTN肺动脉高压的程度。PPHTN患者胃肠道5-HT合成增加导致肺动脉和桡动脉中5-HT水平明显升高,可能是引起肺动脉高压的另一重要原因。

Objective To study the role of endothlin-1（ET-1）,nitric oxide（NO）,thromboxane A2（TXA2）,prostacyclin（PGI2）,5-hydroxytryptamine（5-HT） and transforming growth factor-β1（TGF-β1） on pathogenesis of PPHTN.Methods A case-control study of 6 vasoactive substances in 4 PPHTN patients（P group） and 12 PHT patients（C group） was conducted,and another 10 patients with gastroenteric carcinoma were set as normal control group（N group）.Blood samples from femoral vein,main pulmonary artery and radial collateral artery of each patient studied were collected.Serum concentrations of ET-1,TXB2,5-HT and TGF-β1 were measured using an enzyme linked immunoassay;serum concentration of NO was measured by the method of nitric acid reductase;plasma level of PGF1α was measured with radioimmunoassay.The results of 3 groups were compared and analyzed.Results The ET-1 levels in P group and C group were significantly above normal range.ET-1 concentrations in pulmonary and systemic circulation of C group was about 2.8 times as high as N group,while those of P group were about 4 times as high as N group,and there was statistical significance between P group and C group,especially in pulmonary artery [（270.62±9.03）pg/mL vs（191.56±40.90）pg/mL;t=3.752,P=0.002].The concentrations of NO [femoral vein： P group=（47.49±11.05）μmol/L,C group= 58.83±39.85）μmol/L,N group=（23.07±7.64）μmol/L;pulmonary artery： P group=（49.99±11.79）μmol/L,C group=（59.76±43.63）μmol/L,N group=（23.33±8.02）μmol/L;radial collateral artery： P group=（43.56±9.99）μmol/L,C group=（56.84±36.38）μmol/L;N group=（22.30±6.90）μmol/L] and PGF1α [femoral vein： P group=（439.28±174.58）pg/mL,C group=（423.29±289.63）pg/mL,N group=（83.98±11.94）pg/mL;pulmonary artery： P group=（428.94±145.13）pg/mL,C group=（378.43±214.31）pg/mL,N group=（76.47±11.91）pg/mL;radial collateral artery： P group=（384.42±158.40）pg/mL,C group=（383.65±276.62）pg/mL;N group=（78.27±10.86）pg/mL] in P group and C group were significantly higher than those in N group,but had no difference between P group and C group.The concentration of TXB2 in radial collateral artery of P group was highly above normal range and was significantly higher than that in C group [（111.02±52.58）pg/mL vs（41.59±13.25）pg/mL,t=2.322,P=0.036].The 5-HT level in femoral vein of P group was in normal range and the levels in main pulmonary artery and radial collateral artery were significantly higher than those of N group as well as had statistical significance with those of C group（t=10.04,P0.01;t=6.994,P0.01）.TGF-β1 had a normal test results in all groups.Conclusion The extremely elevated ET-1 level and imbalance between ET-1 and NO probably play a key role in the pathogenesis of PPHTN.PGI2 and TXA2 are not the launching factors of PPHTN,but TXA2 may worsen pulmonary hypertension of PPHTN.Overproduction of 5-HT in alimentary tract,which causes elevation of 5-HT level in pulmonary artery and radial collateral artery,may be another important cause of PPHTN.