硫化氢供体对高肺血流性肺动脉高压大鼠肺动脉胶原含量及代谢的影响

目的探讨硫化氢供体硫氢化钠(sodium hydrosulfide,NaHS)对高肺血流性肺动脉高压大鼠肺动脉胶原含量及代谢的影响。方法32只♂SD大鼠随机分为分流组(n=8)、分流+NaHS组(n=8)、假手术组(n=8)和假手术+NaHS组(n=8)。对分流组和分流+NaHS组大鼠行腹主动脉-下腔静脉穿刺建立高肺血流动物模型。分流11wk后,以右心导管法测定大鼠肺动脉收缩压(systolic pulmonary arteryp ressure,SPAP)、以敏感硫电极法测定肺组织硫化氢(hydro-gen sulfide,H2S)含量、以免疫组织化学法测定肺动脉胶原Ⅰ和胶原Ⅲ、基质金属蛋白酶-13(matrix metalloproteinase,MMP-13)及其抑制物-1(tissue inhibitor of metalloproteinase,TIMP-1)的表达。结果分流11wk后,大鼠SPAP明显增高(P<0.05);肺组织H2S含量明显降低(P<0.05);应用NaHS干预11wk后,分流+NaHS组大鼠H2S含量明显升高,而SPAP明显降低(P<0.05);分流+NaHS组大鼠胶原Ⅰ和胶原Ⅲ蛋白表达比分流组明显降低(P<0.05);分流+NaHS组大鼠MMP-13、TIMP-1的蛋白表达及MMP-13/TIMP-1比值比分流组明显升高(P<0.05)。结论NaHS可能通过增加肺动脉壁胶原成分的降解、减少胶原含量,从而在高肺血流性肺动脉高压形成中发挥调节作用。

Impact of hydrogen sulfide donor on the content and metabolism of collagen in rats with pulmonary hypertension induced by high pulmonary blood flow

Aim The study was designed to explore the possible impact of sodium hydrosulfide NaHS on the content and metabolism of collagen in rats with pulmonary hypertension induced by high pulmonary blood flow. Methods Thirty-two male SD rats, weighing 140~160 g, were randomly divided into 4 groups, shunt group (n=8), shunt+NaHS group (n=8), sham group (n=8) and sham+NaHS group (n=8). Rats in shunt group and shunt+NaHS group were subjected to an abdominal aorta-inferior vena cava shunt to create an animal model of high pulmonary flow. In the sham group and sham+NaHS group, rats experienced the same experimental processes except the shunting procedure. After 11 weeks of experiment, systolic pulmonary artery pressure (SPAP) of rats was detected using a right cardiac catheterization procedure. Lung tissue hydrogen sulfide(H2S) content of rats was determined by a modified sulfide electrode method. Pulmonary artery collagen Ⅰ,collagen Ⅲ,MMP-13 and TIMP-1 protein expression of rats was investigated by immunohistochemistry.Results After 11 weeks of experiment, SPAP increased significantly, whereas lung tissue hydrogen sulfide(H2S) content decreased significantly in rats of shunt group as compared with those of sham group (P<0.05). After administration of NaHS for 11 weeks, lung tissue H2S content increased significantly, whereas SPAP decreased significantly in rats of shunt+NaHS group as compared with those of shunt group (P<0.05). In contrast to rats in shunt group, pulmonary artery collagen Ⅰ and collagen Ⅲ protein expression in rats of shunt+NaHS group decreased significantly, respectively (P <0.05). Compared with rats of shunt group, pulmonary artery MMP-13, TIMP-1 and the ratio of MMP-13/TIMP-1 in rats of shunt+NaHS group up-regulated significantly (P<0.05). Conclusion NaHS might play regulatory role in the development of pulmonary hypertension in rats by decreasing the content of collagen resulting from catabolism of collagen.