L-精氨酸对低氧性肺动脉高压大鼠肺动脉平滑肌细胞凋亡的影响

Impact of L-Arginine on apoptosis of smooth muscle cells in pulmonary artery of hypo-xic pulmonary hypertensive rats

目的 探讨L-精氨酸(L-Arg)对低氧性肺动脉高压大鼠不同节段肺动脉平滑肌细胞凋亡的影响。方法 将Wistar大鼠(n=19)随机分为对照组(n=7)、低氧组(n=6)及低氧+L-Arg组(n=6)。经右心导管法测定各组大鼠肺动脉压力和右室(RV)/左室+室间隔(LV+S)比值,以分光光度法间接测定血浆一氧化氮(NO)含量,通过TUNEL法检测各组大鼠不同节段的肺动脉平滑肌细胞凋亡数目,并计算肺动脉平滑肌细胞凋亡数目与肺动脉平滑肌细胞数目比值。结果 低氧组大鼠肺动脉平均压(PAMP)显著高于对照组[(2.71±0.29)kPa vs(2.05±0.14)kPa,P<0.01],低氧+L-Arg组大鼠的PAMP显著低于低氧组[(2.23±0.18)kPa vs(2.71±0.29)kPa,P<0.05];低氧组大鼠RV/(LV+S)比值显著高于对照组[(0.42±0.03)kPa vs(0.30±0.05)kPa,P<0.01],低氧+L-Arg组大鼠RV/(LV+S)比值显著低于低氧组[(0.36±0.02)kPa vs(0.42±0.03)kPa,P<0.01];低氧组大鼠血浆NO含量明显低于对照组[(3.54±0.47)μmol/L vs(4.79±0.17)μmol/L,P<0.05],低氧+L-Arg组大鼠血浆NO含量显著高于低氧组[(5.21±0.26)μmol/L vs(3.54±0.47)μmol/L,P<0.01];低氧组大鼠与终末细支气管伴行的肺动脉和与呼吸细支气管伴行的肺动脉平滑肌细胞凋亡数目与平滑肌细胞数目比值明显低于对照组[(0.051±0.

Objective To investigate the impact of L-arginine(L-Arg) on apoptosis of smooth muscle cells in different segments of pulmonary arteries in hypoxic pulmonary hypertensive rats. Methods Male Wister rats (n = 19) were randomly divided into conrtol group (n = 7),hypoxia group(n = 6) and hypoxia with L-Arg group (n = 6). Pulmonary arterypressure of each rat was measured by using a right cardiac catheterization procedure. Dry weight of right ventricle (RV), left ventricle with septum(LV + S) were determined and RV/(LV+S) ratio was calculated. Plasma concentration of nitric oxide (NO) was measured indirectly via spec-trophotometry. The account of apoptotic smooth muscle cells was detected by the TdT-mediated dUTP-biotin nick-end labeling (TUNED and percentage of apop-totic smooth muscle cells to smooth muscle cells in the same segment of pulmonary artery was calculated. Results Pulmonary artery mean pressure(PAMP) was significantly higher in rats of hypoxia group than that of control group[(2. 71 + 0. 29)kPa vs(2. 05+0. 14)kPa,P<0. 01] and it was much lower in rats of hypoxia with L-Arg group than that of hypoxia group[(2.23+0. 18)kPa vs(2. 71+0. 29) kPa,P<0.05]; Weight of RV/(LV + S) ratio was increased in rats of hypoxia group compared with that of control group [( 0. 42 + 0. 03 ) vs ( 0. 30 + 0. 05 ), P < 0. 01 ]. While it was decreased in rats of hypoxia with L-arginine group compared with that of hypoxia group [(0. 36+0. 02) vs (0. 42 + 0. 03 ) , P < 0. 01 ]. Plasma concentration of NO was markedly deceased in comparison with control group [(3- 54 +0. 47)nmol/L vs(4. 79+0. 17)umol/L,P< 0. 05] and it was much higher in rats of hypoxia with L-Arg group than that of hypoxia group [( 5. 21 + 0. 26 ) umol/L vs (3. 54+0. 47)umol/L,P<0. 01]. The percentage of apoptotic smooth muscle cells to smooth muscle cells in pulmonary arteries associated with terminal bronchioli or respiratory bronchioli was markedly deceased in rats of hypoxia group compared with that of control group [(0. 051 + 0. 016) vs (0. 104+0. 019),P<0. 05]. While,it was much higher in rats of hypoxia with L-Arg than either of control group or hypoxia group [(0.162 + 0.076) vs ( 0. 104 + 0. 019 ) , P < 0. 05; ( 0. 162 + 0. 076 ) vs (0. 051 + 0. 016) , P < 0. 01, respectively]. Conclusion L-Arg plays an important regulatory role in the smooth muscle cell apoptosis of pulmonary arteries of hypoxic pulmonary hypertension through initiating NO synthesis in rats.