CAJ | 학술논문

为观察硫化氢(hydrogen sulfide,H2s)在脂多糖(1ipopolysaccharide,LPS)引起的肺动脉高压中的作用,应用离体血管环张力测定方法测定肺动脉反应性,采用生物化学方法测定肺动脉组织中H2S产出率和胱硫醚-γ-裂解酶(cystathionine γ-lyase,CSE)活性,定量PCR方法测定肺动脉组织中CSE表达水平.结果如下:(1)与对照组相比,LPS可显著升高肺动脉平均压(mean pulmonary arterial pressure,mPAP)[(1.82±0.29)kPa vs(1.43±0.26)kPa,P<0.01],降低肺动脉组织中H2S产出率[(26.33±7.84)vs(42.92±8.73)pmoFg wet tissue per minute,P<0.01]和ACh诱导的肺动脉内皮依赖性舒张反应[(75.72±7.22)%vs(86.40±4.40)%,P<0.01];(2)NariS可部分逆转上述变化,而PPG加剧上述变化;(3)CSE活性和CSE mRNA表达的变化与H2S产出率的变化相同.结果提示,LPS对内皮依赖性舒张反应的抑制导致肺动脉高压的发生,此作用可能与H2S有关.
위관찰류화경(hydrogen sulfide,H2s)재지다당(1ipopolysaccharide,LPS)인기적폐동맥고압중적작용,응용리체혈관배장력측정방법측정폐동맥반응성,채용생물화학방법측정폐동맥조직중H2S산출솔화광류미-γ-렬해매(cystathionine γ-lyase,CSE)활성,정량PCR방법측정폐동맥조직중CSE표체수평.결과여하:(1)여대조조상비,LPS가현저승고폐동맥평균압(mean pulmonary arterial pressure,mPAP)[(1.82±0.29)kPa vs(1.43±0.26)kPa,P<0.01],강저폐동맥조직중H2S산출솔[(26.33±7.84)vs(42.92±8.73)pmoFg wet tissue per minute,P<0.01]화ACh유도적폐동맥내피의뢰성서장반응[(75.72±7.22)%vs(86.40±4.40)%,P<0.01];(2)NariS가부분역전상술변화,이PPG가극상술변화;(3)CSE활성화CSE mRNA표체적변화여H2S산출솔적변화상동.결과제시,LPS대내피의뢰성서장반응적억제도치폐동맥고압적발생,차작용가능여H2S유관.
The purpose of the present study was to explore the role of endogenous hydrogen sulfide (H2S) in pulmonary arterialhypertension induced by endotoxin. Adult male Sprague-Dawley (SD) rats were randomly divided into four groups: Control group(0.5 mL/kg body weight of normal saline, i.v.), lipopolysaccharide (LPS)-treated group (5 mg/kg body weight of LPS, i.v.), LPS+NaHS(5 mg/kg body weight of LPS, i.v., and 28 μmol/kg body weight of NariS, i.p.) and LPS + PPG group (5 mg/kg body weight of LPS, i.v.,and 30 μmol/kg body weight of PPG, i.p.). Rats were anesthetized with 20% urethane (1 g/kg body weight, i.p.). A polyethylene catheterwas inserted into the pulmonary artery through the fight external jugular vein to measure the mean pulmonary arterial pressure (mPAP)for 7 h, and then the pulmonary artery was isolated rapidly by the method described previously. Pulmonary arterial activity was detected.H2S concentration and cystathionine γ-lyase (CSE) activity in pulmonary artery tissues were determined by biochemical method. CSEmRNA expression was detected by competitive reverse transcriptase-polymerase chain reaction (RT-PCR). Compared with control,LPS significantly increased mPAP [(1.82±0.29) kPa vs (l.43±0.26)kPa, P<0.01], decreased H2S production [(26.33±7.84) vs (42.92±8.73)pmol/g wet tissue per minute, P<0.01), and reduced endothelium-dependent relaxation response [(75.72±7.22)% vs (86.40±4.40)%,P<0.01) induced by ACh (1 x 10-6 mol/L). These effects were partly reversed by co-administration of NariS and enhanced by co-administration of PPG. Both CSE activity and CSE mRNA expression were consistent with H2S production. It is suggested that theinhibitory effect of LPS on endothelium-dependent relaxation results in pulmonary hypertension, which might be mediated through H2S.