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目的探讨人参皂苷Rg1对野百合碱(MCT)诱导的大鼠肺动脉高压(PAH)的影响和作用机制。方法将55只SD雄性大鼠随机分为对照组、模型组、Rg1组、Rg1+L-NAME组、L-arg组、LNAME+L-arg组,除对照组5只外各组均为10只。对照组皮下注射等体积生理盐水,其余各组均皮下注射MCT(50 mg·kg-1)复制PAH模型,3 d后按分组给药,Rg1剂量为15 mg·kg-1·d-1(ip),L-NAME为20 mg·kg-1·d-1(ig),L-arg为200 mg·kg-1·d-1(ip),连续21 d。每周测量体重,末次给药后2 h麻醉,导管法测定平均肺动脉压(mPAP),计算右心肥厚指数(RVHI),HE染色观察肺小动脉病理改变,分别经比色法和ELISA测定血清中NO和cGMP含量。结果与对照组相比,模型组大鼠体重下降,mPAP和RVHI显著增高(P<0.05),肺小动脉重构明显,经Rg1治疗后各指标均有好转(均P<0.05)。模型组大鼠血清中NO和cGMP含量较对照组低,但未见显著差异(P>0.05),Rg1和L-arg处理后NO和cGMP含量均显著增加(P<0.05),且两者对NO和cGMP的影响可被L-NAME拮抗(P<0.05)。结论人参皂苷Rg1可有效干预MCT诱导的大鼠肺动脉高压,其机制部分与增加NO有关。
Objective To investigate the effect and mechanism of ginsenoside Rg1 on pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT) in rats. Methods Fifty-five SD male rats were randomly divided into control group, model group, Rg1 group, Rg1 + L-NAME group, L-arg group and LNAME + L-arg group. only. In the control group, an equal volume of normal saline was injected subcutaneously, and the other groups were subcutaneously injected with MCT (50 mg · kg -1) to replicate the PAH model. After 3 days, the rats were treated with Rg 1 at a dose of 15 mg · kg -1 · d -1 ip). L-NAME was 20 mg · kg-1 · d-1 (ig) and L-arg was 200 mg · kg-1 · d-1 ip for 21 days. The body weight was measured weekly, anesthetized 2 h after the last administration, mean pulmonary arterial pressure (mPAP) was measured by catheterization method, and right ventricular hypertrophy index (RVHI) was calculated. Pathological changes of pulmonary arterioles were observed by HE staining. NO and cGMP content. Results Compared with the control group, the body weight, mPAP and RVHI of the model group were significantly increased (P <0.05). The remodeling of pulmonary arterioles was obvious. All the indexes improved after Rg1 treatment (all P <0.05). The content of NO and cGMP in serum of model group was lower than that of control group, but there was no significant difference (P> 0.05). The contents of NO and cGMP in Rg1 and L-arg group were significantly increased (P <0.05) The effects of NO and cGMP were antagonized by L-NAME (P <0.05). Conclusions Ginsenoside Rg1 can effectively interfere with MCT-induced pulmonary hypertension in rats, and its mechanism is partially related to the increase of NO.