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目的:观察氟伐他汀对大鼠实验性肺动脉高压(PAH)的预防作用,并探讨caveolin-1与PAH的关系。方法:98只Wistar大鼠被随机分为3组:M+F组大鼠首先给予野百合碱(MCT,30 mg/kg)皮下注射和氟伐他汀(1 mg/kg)灌胃,每日各1次,连续2周,自第2周末至第6周末继续按氟伐他汀初始给药方案灌胃而不再进行MCT皮下注射。MCT组大鼠给予每日1次MCT(30 mg/kg)皮下注射,每日1次,且自第1周开始至第6周末给予同氟伐他汀等体积的生理盐水灌胃,每日1次。Saline组给予生理盐水皮下注射或灌胃。自实验开始间隔2周测定各组大鼠平均肺动脉压(mPAP)、右心室肥厚指数(RVHI)及肺组织caveolin-1蛋白相对含量。结果:MCT组大鼠实验第4周末mPAP和RVHI值均较Saline组显著增高。M+F组大鼠至第6周末才出现mPAP明显升高,但观察期间该组大鼠RVHI与Saline组比较差异无统计学意义。MCT组大鼠实验第2周末caveolin-1蛋白相对含量较Saline组显著降低(P<0.05),至第4周末和第6周末,caveolin-1表达进一步下调,而M+F组未观察到有统计学意义的caveolin-1表达下调。结论:Caveolin-1表达下调是大鼠实验性PAH形成的重要原因,氟伐他汀预防大鼠肺动脉高压形成的机制与其抑制caveolin-1表达下调有关。
Objective: To observe the preventive effect of fluvastatin on experimental pulmonary hypertension (PAH) in rats and to explore the relationship between caveolin-1 and PAH. Methods: A total of 98 Wistar rats were randomly divided into 3 groups: M + F group rats were given subcutaneous injection of monocrotaline (MCT, 30 mg / kg) and fluvastatin (1 mg / kg) Once a week for 2 consecutive weeks. From the end of the second weekend to the end of the 6th week, the mice were orally administered with the initial regimen of fluvastatin instead of subcutaneous injection of MCT. The rats in MCT group were injected subcutaneously with MCT (30 mg / kg) once a day once a day, and the same volume of flusvastatin was given intragastrically once a week from the first week to the end of the sixth week Times. Saline group given saline subcutaneously or gavage. The mean pulmonary arterial pressure (mPAP), right ventricular hypertrophy index (RVHI) and the relative content of caveolin-1 protein in lung tissue of rats in each group were measured 2 weeks after the start of the experiment. Results: Compared with Saline group, mPAP and RVHI in MCT group were significantly increased at the end of the 4th week. There was no obvious increase of mPAP in rats in M + F group at the end of the 6th week, but there was no significant difference between RVHI and Saline group in the rats in M + F group. Compared with Saline group, the relative content of caveolin-1 in MCT group was significantly decreased (P <0.05) at the end of the 2nd week. The expression of caveolin-1 was further down-regulated in the 4th and 6th week in the MCT group, but not in the M + F group The statistical significance of caveolin-1 expression was down-regulated. Conclusion: The down-regulation of Caveolin-1 is an important reason for the formation of experimental PAH in rats. The mechanism of fluvastatin in preventing the formation of pulmonary hypertension in rats is related to the down-regulation of caveolin-1 expression.