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目的观察不同时期应用辛伐他汀对野百合碱(MCT)诱导大鼠肺动脉高压(PAH)的改善作用,初步评价早期应用辛伐他汀对PAH的预防效果。方法将24只SD大鼠随机分成4组,每组6只。对照组:d_0腹腔注射生理盐水1次;PAH模型组:d_0腹腔注射MCT(50 mg/kg)1次;早期干预组:腹腔注射MCT(50 mg/kg)d–7~d~(–1)辛伐他汀(20 mg·kg~(–1)·d~(–1))灌胃,d_0腹腔注射MCT(50 mg/kg)1次,d1~14辛伐他汀灌胃;后期干预组:d0腹腔注射MCT(50 mg/kg),d15~35辛伐他汀(20 mg·kg~(–1)·d~(–1))灌胃。d_(36)通过右心导管测大鼠右心室收缩压(RVSP)和平均肺动脉压(m PAP),处死大鼠后分离心肺,测定右心室肥厚指数(RVHI)和肺小动脉中膜厚度百分比(WT%),进行肺小动脉周围炎症评分。结果与PAH组比较,早期干预组及后期干预组RVSP、m PAP、RVHI、WT%得到显著改善(P<0.01),肺小动脉周围炎症评分降低(P<0.05);与后期干预组比较,早期干预组m PAP、RVSP改善更明显(P<0.05),WT%下降更显著(P<0.01),而RVHI、肺小动脉周围炎症评分无显著差异(P>0.05)。结论辛伐他汀早期及后期干预均可改善MCT诱导PAH大鼠RVSP、m PAP及WT%的恶化,早期干预较后期干预效果更显著。
Objective To observe the effects of simvastatin on pulmonary hypertension (PAH) induced by monocrotaline (MCT) in different periods and to evaluate the preventive effect of simvastatin on PAH. Methods Twenty-four SD rats were randomly divided into 4 groups with 6 rats in each group. The rats in the early intervention group were given intraperitoneal injection of MCT (50 mg / kg) for 7 d (-1), while the rats in the control group were injected intraperitoneally with normal saline (d 0) ) And simvastatin (20 mg · kg -1 · d -1) were intragastrically administrated intraperitoneally (ip). MCT (50 mg / kg) : d0 intraperitoneal injection of MCT (50 mg / kg), d15 ~ 35 simvastatin (20 mg · kg -1 · d -1) intragastrically. Right ventricular systolic pressure (RVSP) and mean pulmonary arterial pressure (m PAP) were measured by right heart catheterization. Heart and lungs were isolated from rats and the percentages of right ventricular hypertrophy index (RVHI) and pulmonary arteriole medial thickness (WT%), pulmonary inflammation around the score. Results Compared with PAH group, RVSP, m PAP, RVHI and WT% in early intervention group and late intervention group were significantly improved (P <0.01), inflammatory score of pulmonary arterioles was decreased (P <0.05); Compared with late intervention group, In the early intervention group, m PAP, RVSP improved more significantly (P <0.05), WT% decreased more significantly (P <0.01), while RVHI, pulmonary arteriole inflammation score had no significant difference (P> 0.05). Conclusion Both early and late intervention with simvastatin can improve the RVSP, m PAP and WT% of MCI-induced PAH rats, and the effect of early intervention is more significant than the latter.