内源性硫化氢对大鼠高肺血流性肺动脉高压的调节作用

Regulatory role of endogenous hydrogen sulfide in pulmonary hypertension induced by high pulmonary blood flow in rats

目的应用内源性硫化氢(hydrogensulfide,H2S)生成酶胱硫醚-γ-裂解酶(cystathionineγ-lyase,CSE)的抑制剂炔丙基甘氨酸(propargylglycine,PPG),探讨H2S在大鼠高肺血流性肺动脉高压形成中的作用。方法雄性SD大鼠25只,体重120～140g,随机分为分流组(n=9)、分流+PPG组(n=8)和假手术组(n=8)。分流组及分流+PPG组大鼠经腹主动脉—下腔静脉穿刺术建立高肺血流动物模型,分流+PPG组大鼠腹腔内注射PPG37.5mg/(kg·d),分流组与假手术组大鼠每日给予等量生理盐水。分流术后4周,采用右心导管法测量各组大鼠肺动脉平均压(meanpulmonarypressure,MPAP),用敏感硫电极法测量大鼠血浆和肺组织H2S含量,分别计算大鼠心脏组织右心室/左心室+室间隔(rightventricle/leftventricle+septum,RV/LV+SP)和心脏重量/体重(heartweight/baseweight,HW/BW)的值。结果分流术后4周,分流组大鼠MPAP与假手术组比较差别无显著性;分流+PPG组大鼠MPAP较分流组及假手术组分别升高了17.70%和21.79%(P<0.05);分流组血浆H2S含量比假手术组明显升高(50.12±6.13vs45.16±5.56,P<0.05);分流+PPG组大鼠血浆H2S含量明显低于分流组和假手术组(38.56±4.98vs50.12±6.13、38.56±4.98vs45.16±5.56,P均<0.05);分流+PPG组大鼠RV/LV+SP和HW/BW明显高于分流组和假手术组(0.33±0.03vs0.30±0.03、0.33±0.03vs0.29±0.02,P<0.05)。结论内源性H2S在高肺血流性肺动脉高压形成过程中发挥保护性调节作用。

Objective Using propargylglycine （PPG）,the inhibitor of cystathionine γ-lyase （CSE） which is the key enzyme to generate endogenous hydrogen sulfide（H2S）,to explore the regulatory role of H2S in pulmonary hypertension induced by high pulmonary flow in rats. Methods Twenty-five male SD rats with the weight of 120 - 140 g were randomly divided into shunt group in = 9）,shunt＋PPG group in = 8） and sham group in = 8） respectively. Rats in shunt group were subjected to an aorta caval shunt to create the animal model of high pulmonary flow. Rats in shunt＋PPG group were injected with PPG 37.5 mg/（kg·d）,and rats in both of shunt and sham groups were given equivalent normal saline per day intraperitoneally. The detection of H2S content in both of serum and pulmonary tissue with sensitive sulfur-electrode method, the measurement of mean pulmonary artery pressure （MPAP） with right cardiac catheterization, and the calculation of right ventricle （RV）/left ventricle （LV） with septurn （SP）,heart weight（HW）/base weight（BW） of each rat were undertaken after 4 weeks. Results H2S content in serum increased significantly in shunt group [（50.12 ± 6.13）μmol/L] in comparison with that in sham group [（45.16 ± 5.56）μmol/L] （P 〈 0.05）, whereas decreased in shunt＋PPG group [（38.56 ± 4.98）μmol/L] in comparison with those in both of sham and shunt groups （P 〈 0.05 for all）. MPAP in shunt＋PPG group increased 17.7% and 21.79% in comparison with those in both of sham and shunt groups, respectively （P 〈 0.05）, and there was no significant difference in MPAP between sham and shunt groups （P 〉 0.05）. RV/LV＋SP and HW/BW in shunt＋PPG group （0.33 ± 0.03,4.11 ± 0.83） increased significantly in comparison with those in both of sham （0.29 ± 0.02,2.75 ± 0.18） and shunt groups （0.30 ± 0.03,3.30 ± 0.56）（P 〈 0.05 for all）,and there was no significant difference in RV/LV＋SP and HW/BW between sham and shunt groups （P 〉 0.05）. Conclusions Endogenous H2S system may play a protective role in the regulation of pulmonary hypertension induced by high pulmonary blood flow.