摘要
目的：探讨ATP敏感性钾通道开放剂盐酸埃他卡林对慢性低氧性大鼠肺动脉内皮细胞和脉动脉压力及右心室肥厚的影响。 方法：①实验于2002-05／08在南京医科大学药理实验室完成。选用雄性清洁级SD大鼠40只。大鼠被随机分为4组：对照组和低氧组[给予生理盐水1．5mg／(kg·d)灌胃]及埃他卡林0．75和1．50mg／(kg·d)治疗组[每天缺氧前30min分别灌胃给予盐酸埃他卡林0．75mg／(kg·d)和1．50mg／(kg·d)]，每组10只。②低氧处理：将低氧组和2个治疗组大鼠置于常压低氧舱内，向舱内充入氮气，使舱内氧浓度稳定于(10±0．5)％，8h／d，每周6d，持续4周。用微型压力传感器测定平均肺动脉压，计算出右心室质量／(左心室质量+室间隔质量)，反映右心室质量的变化，以确定有无右心室肥厚。③分别在光镜和透射电子显微镜下观察肺血管内皮细胞结构和肺小动脉内皮细胞超微结构改变。④组间差异用等方差t检验。 结果：大鼠40只均进入结果分析。①平均肺动脉压和右心室质量／(左心室质量+室间隔质量)：低氧组明显高于对照组(P<0．01)，埃他卡林0．75和1．50 mg／(kg·d)治疗组明显低于低氧组(P<0．01)。②光镜下，低氧组大鼠肺小动脉内皮细胞肥大、增生，两种治疗组中大鼠肺小动脉内皮细胞基本恢复正常。③电镜下，低氧组大鼠肺小动脉内皮细胞损伤脱落、胶原增多，治疗组大鼠肺小动脉内皮损伤、中膜平滑肌细胞和胶原纤维增生明显轻于低氧组。 结论：盐酸埃他卡林可抑制低氧性肺动脉内皮细胞的增殖脱落，减轻低氧所致肺动脉高压和右心室肥厚。
AIM： To explore the effects of ATP sensitive potassium channel opener （KATPCO） iptakalim hydrochloride on pulmonary arterial endothelial cells and arterial pressure with thickening of right ventricle in chronic hypoxic rats. METHODS： ① The experiment was conducted at the laboratory of pharmacology of Nanjing Medical University from May to August 2002, Forty clean grade SD male rats were selected, and divided randomly into 4 groups： control group, hypoxic group [The rats were treated with 1.5 mg/kg per day saline with gastric perfusion] and 0.75 and 1.50 mg/kg per day iptakalim treatment group [The rats were treated with 0.75 and 1.50 mg/kg per day iptakalim hydrochloride with gastric perfusion, respectively, at 30 minutes before hypoxia every day] with 10 rats in each group. ② Hypoxia disposal： The rats in the hypoxic group and two rats in the treatment group were put into hypoxic inboard with normal pressure, and nitrogen fumes were filled into inboard, making the concentration of oxygen inboard stable to （10±0.5）%, 8 hours per day, 6 days per week for 4 weeks. The mean pulmonary artery pressure （mPAP） was detected, and mass of right ventrcle/（mass of left ventricle ＋ mass of interventricular septum） was calculated, and the changes of mass of right ventricle were gotten with mini-pressure transducer in order to define whether the right ventricle became thickening or not. ③ The changes of structure of pneumoangiogram endothelial cell and ultrastructure of pulmonary arteriole endothelial cell were observed under light microscope and transmission electron microscope （TEM）, respectively. ③ The difference among groups was detected with equal variance t-test. RESULTS： Totally 40 rats were involved in the result analysis. The mPAP and mass of right ventricle/（mass of left ventricle ＋ mass of interventricular septum）： It was significantly higher in the hypoxic group than that in the control group （P 〈 0.01 ）, and it was lower in the 0.75 and 1.50 mg/kg per day iptakalim treatment group than that in the hypoxic group （P 〈 0.01 ）. ② Under light microscope, the pulmonary arteriole endothelial cell in rats of hypoxic group was hypertrophy and hyperplasia, and the pulmonary arteriole endothelial cell in rats of the two treatment group recovered to normality mostly. ③ Under electron microscope, the pulmonary arteriole endothelial cell in rats of hypoxic group was damaged and dropped with many collagens, and the pulmonary arteriole endothelial cell was injured; The media smooth muscle cell and hyperplasia of collagen fibers were significantly lightener than those in the hypoxic group. CONCLUSION： The iptkalim hydrochloride can inhibit hypoxic pulmonary arterial endothelial cells proliferation and reduce pulmonary hypertension and thickening of reght ventricle induced by hypoxia.
出处
《中国临床康复》
CSCD
北大核心
2005年第35期94-96,共3页
Chinese Journal of Clinical Rehabilitation
基金
江苏省科委社会发展基金(BJ2000051)江苏省教育厅基金(00KJB320009)~~
