CAJ | 학술논문

目的:研究低O_2高CO_2性肺动脉高压时大鼠肺组织内硫化氢体系的变化及川芎嗪对其的干预作用.方法:将30只SD大鼠随机分为3组,每组10只.正常对照组(C组)、低O_2高CO_2组(HH组)、低O_2高CO_2+川芎嗪组(HH+LTZ组).监测其血流动力学变化,光镜观察肺细小动脉管壁面积/管总面积比值(WA/TA),检测右心室/ 左心室+室间隔(RV/ LV+SP) 比值,原位缺口末端标记法(TUNEL法)观测肺细小动脉凋亡情况,并计算凋亡指数.敏感硫电极法测定血浆H_2S含量及肺组织匀浆胱硫醚-γ-裂解酶(CSE)活性变化.RT-PCR法测定肺组织中CSE基因表达水平.结果:HH组的肺平均动脉压(mPAP)、WA/TA、RV/ LV+SP明显高于C组,HH+LTZ组明显低于HH组(均P<0.01);3组的平均颈动脉压(mCAP)无明显差异(P>0.05).TUNEL法测得HH组、HH+LTZ组的肺细小动脉凋亡指数(AI)显著低于C组(P<0.01), HH+LTZ组肺细小动脉凋亡指数显著高于HH组(P<0.05).血浆硫化氢(H_2S)含量、肺组织匀浆胱硫醚-γ-裂解酶(CSE)活性、肺组织CSE基因表达水平,HH组明显低于C组(P<0.01),HH+LTZ组明显高于HH组(P<0.01).结论:川芎嗪可能通过上调CSE基因表达,增加CSE的活性,提高H_2S水平,从而降低低O_2高CO_2性肺动脉高压.
목적:연구저O_2고CO_2성폐동맥고압시대서폐조직내류화경체계적변화급천궁진대기적간예작용.방법:장30지SD대서수궤분위3조,매조10지.정상대조조(C조)、저O_2고CO_2조(HH조)、저O_2고CO_2+천궁진조(HH+LTZ조).감측기혈류동역학변화,광경관찰폐세소동맥관벽면적/관총면적비치(WA/TA),검측우심실/ 좌심실+실간격(RV/ LV+SP) 비치,원위결구말단표기법(TUNEL법)관측폐세소동맥조망정황,병계산조망지수.민감류전겁법측정혈장H_2S함량급폐조직균장광류미-γ-렬해매(CSE)활성변화.RT-PCR법측정폐조직중CSE기인표체수평.결과:HH조적폐평균동맥압(mPAP)、WA/TA、RV/ LV+SP명현고우C조,HH+LTZ조명현저우HH조(균P<0.01);3조적평균경동맥압(mCAP)무명현차이(P>0.05).TUNEL법측득HH조、HH+LTZ조적폐세소동맥조망지수(AI)현저저우C조(P<0.01), HH+LTZ조폐세소동맥조망지수현저고우HH조(P<0.05).혈장류화경(H_2S)함량、폐조직균장광류미-γ-렬해매(CSE)활성、폐조직CSE기인표체수평,HH조명현저우C조(P<0.01),HH+LTZ조명현고우HH조(P<0.01).결론:천궁진가능통과상조CSE기인표체,증가CSE적활성,제고H_2S수평,종이강저저O_2고CO_2성폐동맥고압.
AIM: To investigate the effect of ligustrazine on hydrogen sulfide (H_2S) system in pulmonary hypertension induced by hypoxic hypercapnia in rats. METHODS: Thirty Sprague-Dawley rats were randomly divided into 3 groups: control group (C), hypoxic hypercapnia group (HH), and hypoxic hypercapnia+ligustrazine group (HH+L). The change of hemodynamics was measured. The ratio of vessel wall area and total area of arteriae pulmonalis were observed under light microscope. The apoptosis of arteriae pulmonalis was tested with TdT-mediated dUTP nick end labeling (TUNEL), and the apoptosis index was calculated. Plasma level of hydrogen sulfide and activity of hydrogen sulfide generating enzymes in homogenates of rat lung tissue were evaluated by sensitive modified sulfide electrode method. Cystathionine-γ-lyase (CSE) mRNA in lung tissues was determined by RT-PCR. RESULTS: The level of mean pulmonary arterial pressure, the ratio of vessel wall area/total area and the right ventricle/left ventricle+septum were significantly higher in HH group than those in C group, and the value was obviously lower in HH+LTZ group than that in HH group (all P<0.01). The mean carotid arterial pressure of 3 groups had no significant difference (P>0.05). The apoptotic index of arteriae pulmonalis in HH group and HH+LTZ group was significantly lower than that in C group, and that in HH+LTZ group was significantly higher than that in HH group (P<0.05 or P<0.01). Plasma level of H_2S, the activity of H_2S generating enzymes in homogenates of rat lung tissue, cystathionine-γ-lyase (CSE) mRNA in lung tissues in HH group were significantly lower than those in C group (all P<0.01), and those in HH+LTZ group were significantly lower than those in HH group (all P<0.01). CONCLUSION: Ligustrazine up-regulates the expression of cystanthionine-γ-splitting enzyme (CSE), enhances the activity of CSE and increases the level of H_2S to prevent pulmonary hypertension induced by hypoxic hypercapnia.