三苯氧胺对低氧性肺动脉高压大鼠平均肺动脉压与IGF-1的影响

目的 :研究三苯氧胺 (TAM )对低氧大鼠平均肺动脉压 (mPAP)与胰岛素样生长因子 1(IGF 1)的影响。方法 :通过建立低氧性肺动脉高压 (HPH)大鼠模型 ,观察TAM对HPH和IGF 1的作用 ;采用ISH、IHC检测IGF 1及其受体的表达并进行定量或半定量分析。结果 :保护实验组及治疗实验组的mPAP与正常对照组比较无显著差异 (P >0 .0 5 ) ,保护实验组的mPAP显著低于保护对照组 (P <0 .0 5 ) ;保护对照组肺小动脉壁IGF 1mRNA、IGF 1RmRNA的表达均较正常组增强 (P <0 .0 5 ) ;保护实验组两者的表达较保护对照组显著减弱 (P <0 .0 5 ) ,而较正常组增强 (P <0 .0 5 ) ;治疗实验组和保护实验组IGF 1多肽表达的灰度扫描值均较保护对照组减弱 (P <0 .0 5 ) ,保护实验组较正常对照组增强 (P <0 .0 5 ) ,而比保护对照组减弱 (P <0 .0 5 )。结论 :TAM对HPH具有明显的保护和治疗作用 ,抑制低氧大鼠肺小动脉壁IGF 1及其受体的mRNA表达、阻抑IGF 1多肽产生是其主要作用机制之一 ;与保护作用相比 ,TAM的治疗作用较弱。

Effect of tamoxifen on mean pulmonary arterial pressure and IGF-1 in hypoxic rats

Objective To study the effect of tamoxifen on mean pulmonary arte rial pressure(mPAP) and insulin-like growth factor-1(IGF-1) in hypoxic rats. Methods Through establishment of models of HPH rat,the effect of tamoxifen on mPAP and IGF -1 was observed,meanwhile the expression of IGF-1 and its receptor was detecte d by ISH and IHC on pulmonary arterioles in rats, and analyzed quantitatively or s emi-quantitatively. Results There were no statistically signif icant differences of mPAP among the protection experiment group, treatment exper ime nt group and normal control group (P>0.05). The mPAP in the protection expe rim ent group was significantly lower than that in the protection control group(P <0. 05). The positive degrees of expression of IGF-1 and its receptor mRNAs in the pulmonary arterioles in protection control group were stronger than those in th e normal control group (P<0.05). The positive degree of those two in the p rote ction experiment group were significantly lower than those in the protection con trol group, more than those in normal control group(P<0.05); The positive degr ee of IGF-1 polypeptide in gray scale scanning in the pulmonary arterioles in t he treatment experiment group and protection experiment group were weaker than t h at in protection control group(P<0.05), while that in the protection experiment g roup was higher than that in the normal control group(P<0.05). C onclusion TAM has apparent effe ct of protection and treatment on hypoxic pulmonary hypertension,through suppre ssing the expression of IGF-1/ its receptor mRNAs and decreasing the production of IGF-1 polypeptide in the pulmonary arterioles in hypoxic rats as one of its mechanism; compared with its protection action, its treatment action was weaker.