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目的探索阿托伐他汀对20mg/kg野百合碱隔周2次腹腔注射诱导的肺动脉高压(PAH)的影响。方法雄性成年SD大鼠96只随机分为3组:空白对照组、PAH组以及阿托伐他汀组。在第0周(第1天)和第1周末(第8天)以野百合碱(20mg/kg)2次腹腔注射建立大鼠PAH模型。首次腹腔注射的同时,阿托伐他汀组大鼠通过灌胃接受10mg/(kg·d)的阿托伐他汀。第2周和第4周末分别检测平均肺动脉压(mPAP)、右心室肥厚指数(RVHI)、管壁厚度占血管外径百分比(WT%)、管壁面积占血管总面积百分比(WA%)、内皮依赖性舒张功能(EDdR)、非内皮依赖性舒张功能(EDiR)。结果野百合碱腹腔注射后第2周末,3组大鼠mPAP差异无统计学意义;在第4周末,与空白对照组比较,PAH组和阿托伐他汀组mPAP明显升高[mPAP:(33.55±3.47)、(25.46±4.04)比(18.91±2.13)mmHg],但阿托伐他汀组低于PAH组(均P<0.05)。野百合碱腹腔注射后的第2周和第4周末,与空白对照组相比,PAH组和阿托伐他汀组WT%、WA%水平较高[第2周:WT%:(42.17±4.12)%、(33.83±1.23)%比(28.95±2.97)%;WA%:(65.91±4.92)%、(58.37±3.42)%比(49.08±2.84)%;第4周:WT%:(55.79±4.15)%、(40.69±2.53)%比(29.38±4.50)%;WA%:(79.75±3.30)%、(64.11±3.18)%比(49.44±6.28)%],但阿托伐他汀组低于PAH组(均P<0.05)。同时,阿托伐他汀显著改善野百合碱腹腔注射后大鼠肺小动脉的EDdR和EDiR;但野百合碱腹腔注射和阿托伐他汀治疗后,血管收缩功能未发生改变。结论以20mg/kg野百合碱隔周2次腹腔注射可以建立稳定的PAH模型。阿托伐他汀通过改善肺动脉血管重塑以及血管舒张功能缓解野百合碱诱导的PAH。
Objective To explore the effect of atorvastatin on pulmonary hypertension (PAH) induced by intraperitoneal injection of 20 mg / kg monocrotaline twice a week. Methods Ninety-six adult male Sprague Dawley rats were randomly divided into three groups: blank control group, PAH group and atorvastatin group. Rat PAH models were established by intraperitoneal injection of monocrotaline (20 mg / kg) twice daily on week 0 (day 1) and day 1 (day 8). At the same time of first intraperitoneal injection, atorvastatin group received atorvastatin 10 mg / (kg · d) by gavage. The mean pulmonary artery pressure (mPAP), right ventricular hypertrophy index (RVHI), percentage of vascular wall thickness to vessel diameter (WT%), percentage of vessel wall area to total vessel area (WA%) were measured at week 2 and week 4, Endothelium-Dependent Diastolic Function (EDdR), Endothelium-Dependent Diastolic Function (EDiR). Results At the end of the second week after intraperitoneal injection of monocrotaline, there was no significant difference in the mPAP between the three groups. At the end of the fourth week, compared with the blank control group, mPAP in the PAH group and atorvastatin group was significantly increased [mPAP: (33.55 ± 3.47, and (25.46 ± 4.04) vs (18.91 ± 2.13) mmHg, respectively), but those in atorvastatin group were lower than those in PAH group (all P <0.05). The percentages of WT% and WA% in PAH group and atorvastatin group were higher than those in the blank control group at week 2 and week 4 after intraperitoneal injection of lily [Week 2: WT%: (42.17 ± 4.12 %, (33.83 ± 1.23)% (28.95 ± 2.97)%; WA% :( 65.91 ± 4.92)%, (58.37 ± 3.42)% vs (49.08 ± 2.84)%; %, (40.69 ± 2.53)% vs (29.38 ± 4.50)%, WA% (79.75 ± 3.30)%, (64.11 ± 3.18)% vs (49.44 ± 6.28)%, respectively. However, atorvastatin group Lower than PAH group (all P <0.05). Meanwhile, atorvastatin significantly improved the EDdR and EDiR of pulmonary arterioles of rats after intraperitoneal injection of monocrotaline. However, vasoconstrictor function did not change after treatment with monocrotaline and atorvastatin. Conclusion A stable PAH model can be established by intraperitoneal injection of 20 mg / kg monocrotaline twice a week. Atorvastatin ameliorates monocrotaline-induced PAH by improving pulmonary vascular remodeling and vasodilation.