L-精氨酸脂质体对慢性低O2高CO2肺血管L-精氨酸转运的影响

目的:探讨慢性低O₂高CO₂对大鼠肺动脉L-精氨酸(L-Arg)转运的影响与L-Arg脂质体的作用。方法:雄性SD大鼠40只,随机分成4组,正常对照组(NC)、单纯低O₂高CO₂组(HH)、低O₂高CO2加L-Arg组(HL)和低O₂高CO₂加L-Arg脂质体组(HP)。将肺动脉孵育,测定其对³H]-L-Arg的摄取率,同时光镜下观察肺细小动脉显微结构的变化。结果:(1)肺动脉平均压(mPAP)、右心室(RV)和左心室加室间隔(LV+S)重量比值(RV/LV+S)比较:HH组明显高于NC组(P<0.05),HP组明显低于HH组及HL组(P<0.01);HL组与HH组相比无显著差别(P>0.05)。(2)肺动脉薄片对0.005mmol/L、0.01mmol/L、0.02mmol/L、0.05mmol/L、0.1mmol/L和0.2mmol/L³H]-L-Arg摄取率比较:HH组明显低于NC组,HL组明显高于HH组;HP组显著高于HH组及HL组(P<0.01)。(3)光镜下HH组肺细小动脉内弹力板扭曲,中膜平滑肌细胞增生,管腔明显狭窄;HP组肺细小动脉内弹力板扭曲明显减轻,中膜平滑肌层变薄,管壁较均匀一致。结论:慢性低O₂高CO₂大鼠肺血管存在L-Arg的转运障碍,用脂质体作为载体可显著提高肺血管对L-Arg的跨膜转运,L-Arg脂质体治疗慢性肺动脉高压具有潜在临床应用价值。

Effect of L-arginine liposome on L-arginine transport of pulmonary artery in rats chronically exposed to hypoxia-hypercapnia

AIM: To investigate the effect of chronic hypoxia-hypercapnia and L-arginine (L-Arg) liposome on L-Arg transport in rats pulmonary artery. METHODS: Forty Sprague-Dawley rats were randomly divided into four groups, normal control group (NC), chronic hypoxia-hypercapnia group (HH), chronic hypoxia- hypercapnia group L-Arg (HL) and chronic hypoxia-hypercapnia group L-Arg liposome (HP). Changes in pulmonary artery L-Arg transport and pulmonary arterial microscopy were observed. RESULTS: (1) The mean pulmonary artery pressure (mPAP) and weight ratio of right ventricle to left ventricle and septum (RV/LV S) in HH group were higher than those in NC group, and in HP group was lower than that in HH group and HL group, but there was no significant difference between HL group and HH group; (2) At 0.005 mmol/L, 0.01mmol/L, 0.02mmol/L, 0.05 mmol/L, 0.1 mmol/L and 0.2mmol/L concentration of L-Arg, the velocity of L-Arg transport in HH group was lower than that in NC group, and in HL group higher than in HH group, and in HP group was much higher than that in HH group and in HL group. (3) Light microscopy showed that vessel well area/total area (WA/TA) and media thickness of pulmonary arterioles (PAMT) were much higher in rats of HH group than those in NC group, WA/TA and PAMT in HP group were obviously improved. CONCLUSION: The above results indicated that there existed a functional disturbance in L-Arg transport of pulmonary artery in rats chronically exposed to hypoxia-hypercapnia, and it was obviously enhanced when liposome was used as L-Arg carrier. Thus, it appears that liposome-L-Arg may have clinical perspective in the treatment of chronic hypoxic pulmonary hypertension.