一氧化氮途径介导人参总皂苷对大鼠右室肥厚的抑制作用

目的: 观察人参总皂苷(TG)对野百合碱(MCT)所致大鼠右心室肥厚的影响并探讨其与一氧化氮途径的关系. 方法: 雄性SD大鼠随机分为:正常对照组、模型组、TG低、中、高剂量组(20,40,60 mg·kg^-1·d^-1)以及L-精氨酸组(L-arg,200 mg·kg^-1·d^-1,L-a组);另外,为探讨TG的作用与NO释放的关系,另设TG+L-N(NOS合酶抑制剂N^G-硝基-L-精氨酸-甲酯,L-NAME)组和L-a+L-N组.在腹腔注射TG 40 mg·kg^-1·d^-1或L-arg 200 mg·kg^-1·d^-1的同时分别灌胃NOS抑制剂L-N 20 mg·kg^-1·d^-1,各组动物均给药18 d.测定各组大鼠的右心室收缩压(RVSP)、右室肥厚指数(RVHI)、右心重/体重(RVW/BW);透射电镜观察心肌细胞超微结构的改变;硝酸还原法检测心肌组织NO₂^-/ NO₃^-的含量;Real time RT-PCR检测心肌组织心房利钠因子(ANF)、内皮型一氧化氮合酶(eNOS)mRNA的表达. 结果: TG低、中、高剂量和L-arg预防给药均使RVSP,RVSP,RVHI,RV/BW及ANF mRNA表达明显降低(P<0.05),改善细胞线粒体肿胀、变性,L-N能阻止L-arg对上述指标的影响,而同样剂量的L-N并不能影响TG 40 mg·kg^-1对上述指标的降低作用;TG 20,40 mg· kg^-1不影响eNOS mRNA的表达,但60 mg· kg^-1可提高eNOS mRNA的表达. 结论: TG能明显改善MCT诱导的大鼠右心室肥厚,其抗心肌肥厚作用部分是通过NO途径实现的.

Inhibitory effect of nitric oxide-induced total ginsenosides on right ventricular hypertrophy in rats

Objective: To observe the effect of total ginsenosides (TG) on right ventricular hypertrophy induced by monocrotaline (MCT) in rats, and study its relationship with the nitric oxide pathway. Method: Male Sprague Dawley rats were randomly divided into the control group, the MCT model group, TG-treated (20, 40, 60 mg·kg^-1·d^-1) groups, and the L-arginine (L-arg) 200 mg·kg^-1·d^-1 group. Besides, to study TG's effect and its relationship with NO release, TG+L-N and L-a+L-N groups were also set, intraperitoneally injected with TG 40 mg·kg^-1·d^-1 and L-arg 200 mg·kg^-1·d^-1, and orally administered with NOS inhibitor L-NAME 20 mg·kg^-1·d^-1. After all of the groups were given drugs for 18 d, their right ventricular peak systolic pressure (RVSP) ventricular hypertrophy index (RVHI) and RVW/BW were determined. Ultra-structure of myocardial cells was observed with transmission electron microscope. The NO₂^-/NO₃^- content in myocardial tissues were detected with the nitrate reduction method. ANF and eNOS mRNA expressions in right ventricle tissues were detected by using real-time RT-PCR. Result: Low, middle and high doses of TG and L-arg preventive administration could significantly reduce RVSP, RVHI, RVW/BW and ANF mRNA expressions (P<0.05), and ameliorate cellular mitochondrial swelling and degeneration. L-NAME could prevent the effect of L-arg on above indexes, whereas L-NAME of the same dose could not impact the reducing effect of TG 40 mg·kg^-1 on above indexes. TG 60 mg·kg^-1 could raise eNOS mRNA expression, but TG 20 mg· kg^-1 and 40 mg· kg^-1showed no effect. Conclusion: TG can significantly attenuate MCT-induced right cardiac hypertrophy in rats. Its anti-hypertrophic effect is partially realized through NO.