法舒地尔对大鼠低氧性肺动脉高压及其肺血管结构重建的影响  

Effects of fasudil on hypoxia-induced pulmonary hypertension and vascular remodeling in rats

作　　者：孙兴珍[1] 田向阳[1] 

机构地区：[1]南京医科大学附属淮安第一医院儿科,江苏淮安223300

出　　处：《临床儿科杂志》2008年第5期421-424,共4页Journal of Clinical Pediatrics

摘　　要：目的探讨Rho激酶抑制剂法舒地尔对大鼠低氧性肺动脉高压(HPH)及其肺血管结构重建的影响。方法采用常压间断低氧法建立大鼠HPH模型。雄性SD大鼠24只,随机均分为对照组、模型组和法舒地尔干预组。测各组大鼠平均肺动脉压力(mPAP)、平均颈动脉压力(mCAP)、右心室肥厚指数(RVHI);光镜下结合图像分析进行肺血管结构重建观察;透射电镜观察肺小动脉内皮细胞超微结构的变化。结果①模型组mPAP、RVHI、肺小动脉管壁厚度与外径比值(WT%)、管壁面积与管总面积比值(WA%)分别为(31.38±1.98)mmHg、0.47±0.03、(31.13±5.74)%、(54.93±3.34)%均明显高于对照组(15.25±0.91)mmHg、0.25±0.02、(13.24±2.03)%、(31.81±3.62)%,P均<0.01;管腔面积与管总面积比值(LA%)为(45.07±3.34)%,明显低于对照组(68.20±3.62)%,P<0.01;透射电镜显示模型组肺小动脉内皮细胞损伤明显,内皮细胞周围平滑肌细胞增生、肿胀,胶原纤维增生。②法舒地尔干预组mPAP、RVHI、WT%、WA%分别为(16.63±1.53)mmHg、0.27±0.02、(17.08±2.24)%、(37.30±3.69)%显著低于模型组(P<0.01),LA%为(62.70±3.69)%明显高于模型组(P<0.01)。法舒地尔干预后肺小动脉内皮细胞损伤、平滑肌细胞及胶原纤维增生均明显减轻。③各组间mCAP差异无统计学意义(F=1.239,P>0.05)。结论法舒地尔对低氧所致的肺动脉高压、右心室肥厚及肺血管结构重建具有较好的预防和逆转作用。Objectives To investigate whether pulmonary vascular remodeling in rats with hypoxic pulmonary hypertension （HPH） could be prevented by treatment with Rho kinase inhibitor fasudil. Methods The rat model of pulmonary hypertension was established by exposing rats to normobaric intermitent hypoxia （（ 10.0 ± 0.5） %02）. Twenty-four Spraque-Dawley male rats were randomly divided into control group, hypexic model group and fasudil treated group （n = 8 each）. The mean pulmonary arterial pressure （mPAP）, mean cervical arterial pressure （mCAP） and right ventricle hypertrophy index （RVHI） were measured and the small pulmonary arterial morphologic changes in the three groups were studied with microscopy for morphometric analysis. Uhrastructure of the pulmonary arteriole endothelial cells was observed by transmission electron microscope. Results The level of mPAP （31.38 ± 1.98） mmHg and RVHI （0.47 ± 0.03） were significantly higher in the hypoxic model group than （15.25 ± 0.91 ） mmHg and （0.25 ± 0.02） in the control group, respectively （P 〈 0.01 ）. Morphometry investigation showed that the ratio of vascular wall thickness to vascular external diameter （WT%） （31.13± 5.74）% and the ratio of vascular wall area to the total area （WA%） （54.93 ± 3.34）% significantly increased in the hypoxic model group. The ratio of vascular lumen area to the total area （LA%） （45.07 ±3.34）% in the hypexic model group was markedly lower than that in the control group （P 〈 0.01 ）. Under transmission electron microscope, the pulmonary arteriole endothelial cells in rats of hypexic model group was damaged and dropped with many collagens. However, in fasudil group mPAP, RVHI, WT%, WA% were （16.63±1.53）mmHg, （0.27± 0.02）%, （17.08 ±2.24）%, （37.30 ± 3.69）% respectively and much lower than those of the hypoxic model group （all P 〈 0.01）. Moreover, the damage of endothelia in pulmonary arteriole and hyperplasia of smooth muscle cells and collagen

关 键 词：法舒地尔 肺动脉高压 肺血管结构重建 大鼠 

分 类 号：R543.2[医药卫生—心血管疾病]