染料木素对野百合碱诱导的大鼠肺动脉高血压的保护作用

Protective effect of genistein on monocrotaline induced pulmonary hypertension in rats by inhibiting oxidative stress

目的研究染料木素对野百合碱引起的肺动脉高血压(PH)模型大鼠的降压作用及机制。方法大鼠随机分组后,模型组及染料木素组大鼠sc 50 mg/kg野百合碱制备PH模型,对照组sc生理盐水。野百合碱注射后第3天,染料木素低、中、高剂量组ig染料木素10、50、100 mg/kg,对照组和模型组大鼠ig给予等体积生理盐水,1次/d,连续2周。末次给药后,采用尾套法测量清醒大鼠尾部动脉血压;小动物生理仪检测大鼠平均心室压和收缩压;荧光实时定量PCR(RT-qPCR)检测血清白细胞介素(IL)-6、IL-8、IL-1β、肿瘤坏死因子-α(TNF-α)、转化生长因子-β(TGF-β)水平;试剂盒测定大鼠血清超氧化物歧化酶(SOD)值及丙二醛(MDA)、总抗氧化能力(T-AOC)和活性氧(ROS)水平。结果与模型组比较,染料木素50、100 mg/kg组动脉血压、右心室收缩压(RVSP)和右心室舒张末期压(RVeDP)均显著下降(P<0.05、0.01);染料木素10、50、100 mg/kg剂量均可显著降低大鼠血清中IL-6、IL-8、IL-1β、TNF-α、TGF-β的表达(P<0.05、0.01);染料木素10、50、100 mg/kg剂量组ROS和MDA水平显著降低,而T-AOC和SOD水平显著增加(P<0.05、0.01)。结论染料木素对野百合碱诱导的PH大鼠具有降低血压的作用,其机制可能与其阻断氧化应激有关。

Objective To study the antihypertensive effect of genistein on monocrotaline-induced pulmonary hypertension(PH) in rats and its mechanism. Methods Rats in the model group and genistein treatment group were randomly divided into two groups. On the first day of the experiment, the rats in the model group and genistein treatment group were subcutaneously injected with monocrotaline at a concentration of 50 mg/kg. The rats in the control group were subcutaneously injected with normal saline. Fifth week after the administration, the rats in the genistein treatment group were orally given genistein of 10, 50, 100 mg/kg. Then the rats in the control group and the model group were randomly divided into two groups and given distilled water or genistein orally to record blood pressure and renal sympathetic nerve activity. The effects of genistein on blood pressure, right ventricular systolic pressure, right ventricular mean pressure and right ventricular hypertrophy index were detected;the effects of genistein on IL-6, IL-8, IL-1β, TNF-α and TGF-β in serum of rats were detected by PCR;the levels of ROS, MDA, T-AOC and SOD in serum were determined. Results Compared with the model group, the levels of arterial blood pressure, right ventricular systolic pressure(RVSP)and right ventricular end diastolic pressure(RVEDP) of Genistein 50, 100 mg/kg group decreased significantly(P < 0.05, 0.01), and the levels of IL-6, IL-8, IL-1β, TNF-α, TGF-β of Genistein 10, 50 and 100 mg/kg group in serum decreased significantly(P < 0.05,0.01), the levels of ROS and MDA decreased of Genistein 10, 50 and 100 mg/kg group significantly, while the levels of T-AOC and SOD increased significantly(P < 0.05, 0.01). Conclusion Genistein can reduce blood pressure in hypertensive rats induced by monocrotaline, and the mechanism may be related to blocking oxidative stress.