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目的:研究虎杖苷(PD)对慢性低压低氧性肺动脉高压模型大鼠的防治作用及其机制。方法:将雄性SD大鼠随机分为6组,即对照组、低压低氧组、预防组(ip 5,10和20 mg.kg-1PD)和阳性对照组(ig1.7 mg.kg-1西地那非)。建立低压低氧性肺动脉高压大鼠模型,观察PD干预21 d后大鼠肺动脉平均压(mPAP),右心肥厚指数RV/(LV+S)和肺血管形态学的改变,以及大鼠血清、肺组织中一氧化氮(NO)含量、一氧化氮合酶(NOS)活性。结果:①检测PD干预21 d大鼠mPAP,RV/(LV+S),PAMT,SMC,WT%和WA%各指标:对照组依次为(18.35±2.39)mmHg,(21.93±1.66)%,(13.49±2.77)μm,(5.91±1.23),(31.04±3.43)%和(42.83±4.36)%;低压低氧组为(32.05±3.19)mmHg,(36.94±2.67)%,(27.91±4.43)μm,(9.32±1.67),(49.41±4.59)%和(71.72±4.64)%,显著高于对照组(P<0.01);PD中、高剂量组和阳性对照组各指标明显低于低压低氧组(P<0.05或P<0.01)。②血清中NO含量、NOS和cNOS活性:对照组依次为(66.34±5.41)μmol.L-1,(23.18±1.44)U.mL-1和(14.51±1.46)U.mL-1;低压低氧组为(41.07±3.71)μmol.L-1,(12.59±1.50)U.mL-1和(7.19±1.85)U.mL-1,显著低于对照组(P<0.01);肺组织匀浆中NO含量、NOS和cNOS活性:对照组依次为(0.397±0.060)μmol.(g prot)-1,(0.752±0.044)U.(mg prot)-1和(0.511±0.064)U.(mg prot)-1;低压低氧组为(0.316±0.046)μmol.(gprot)-1,(0.605±0.069)U.(mg prot)-1和(0.387±0.030)U.(mg prot)-1,显著低于对照组(P<0.01);而PD中、高剂量组和阳性对照组血清和肺组织匀浆中各指标均高于低压低氧组(P<0.05或P<0.01)。结论:PD给药21 d可有效预防大鼠低压低氧导致的肺动脉高压和肺小动脉的结构重建,其作用机制可能与上调血清、肺组织中NO含量和增强NOS活性有关。
Objective: To study the preventive and therapeutic effects of polydatin (PD) on chronic hypobaric hypoxic pulmonary hypertension in rats and its mechanism. METHODS: Male Sprague-Dawley rats were randomly divided into 6 groups: control group, hypobaric hypoxia group, prevention group (ip 5, 10 and 20 mg.kg-1PD) and positive control group (ig1.7 mg.kg-1). Sildenafil). A rat model of hypoxic pulmonary hypertension was established. The mean pulmonary arterial pressure (mPAP), right ventricular hypertrophy index (RV/S), and pulmonary vascular morphology were observed after 21 days of PD intervention. Rat serum, Nitric oxide (NO) content and nitric oxide synthase (NOS) activity in lung tissue. RESULTS: 1 The indexes of mPAP, RV/(LV+S), PAMT, SMC, WT% and WA% in rats treated with PD for 21 days were detected. The control group was (18.35±2.39) mmHg, (21.93±1.66)%, (13.49±2.77) μm, (5.91±1.23), (31.04±3.43)% and (42.83±4.36)%; in hypobaric hypoxia group, (32.05±3.19) mmHg, (36.94±2.67)%, (27.91±4.43) )μm, (9.32±1.67), (49.41±4.59)%, and (71.72±4.64)%, significantly higher than the control group (P<0.01); PD, high dose group and positive control group were significantly lower than low pressure Hypoxia group (P<0.05 or P<0.01). 2 Serum NO levels, NOS and cNOS activity: the control group was (66.34±5.41) μmol.L-1, (23.18±1.44) U.mL-1 and (14.51±1.46) U.mL-1; The oxygen group was (41.07±3.71)μmol.L-1,(12.59±1.50)U.mL-1 and (7.19±1.85)U.mL-1, significantly lower than the control group (P<0.01); The NO content, NOS and cNOS activity in the pulp: the control group was (0.397±0.060) μmol. (g prot)-1, (0.752±0.044) U. (mg prot)-1, and (0.511±0.064) U. Mg prot)-1; hypobaric hypoxia group was (0.316 ± 0.046) μmol. (gprot)-1, (0.605 ± 0.069) U. (mg prot)-1 and (0.387 ± 0.030) U. (mg prot)- 1, significantly lower than the control group (P <0.01); and PD, high-dose group and positive control group serum and lung homogenate indicators were higher than the hypobaric hypoxia group (P <0.05 or P <0.01). CONCLUSION: PD administration for 21 days can effectively prevent pulmonary hypotension and pulmonary arterial remodeling caused by hypobaric hypoxia in rats. The mechanism may be related to up-regulation of NO and increase of NOS activity in serum and lung tissue.