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-东南大学学报医学版

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

单位：1.东南大学附属中大医院呼吸内科,江苏,南京,210009； 2.四川大学华西医学中心,呼吸内科,四川,成都,610041

关键词：三苯氧胺胰岛素样生长因子-1 胰岛素样生长因子-1受体低氧性肺动脉高压大鼠

分类号：R-33, R965

出版年·卷·期（页码）：2004·23·第六期（379-383）

摘要：

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＞0.05),保护实验组的mPAP显著低于保护对照组(P＜0.05);保护对照组肺小动脉壁IGF-1 mRNA、IGF-1RmRNA的表达均较正常组增强(P＜0.05);保护实验组两者的表达较保护对照组显著减弱(P＜0.05),而较正常组增强(P＜0.05);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＜0.05),保护实验组较正常对照组增强(P＜0.05),而比保护对照组减弱(P＜0.05).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.

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.

参考文献：

[1] Voelkel N F, TUDER R M. Cellular and molecular mechanisms in the pathogenesis of pulmonary hypertension. 1995. doi:10.1183/09031936.95.08122129
[2] Jensen D E, RICH C B, TERPSTRA J. Transcriptional regulation of the elastin gene by insulin-like growth factor- Ⅰ involves disruption of Sp1 binding in aortic smooth muscle cells. 1995. doi:10.1074/jbc.270.12.6555
[3] GAGLIDI A R, HENNIG B, COLLIN D C. Antiestrogens inhibit endothelial cell growth stimulated by angiogenic growth factors, 1996
[4] LEE T C, GOLD L I, REIBMAN J. Immunohistochemical localization of transforming growth factor-beta and insulin-like growth factor-I in asbestosis in the sheep model. 1997. doi:10.1007/s004200050132
[5] LEE P K, DURMOWICZ A G, ROESSLER M. Insulin-like growth factor I(IGF- Ⅰ ) stimulates elastin synthesis by pulmonary artery smooth muscle cells,and IGF- Ⅰ production by adventitial fibroblasts is increased by hypoxia, 1989
[6] Huynh H, POLLAK M. Enhancement of tamoxifen-induced suppression of insulin-like growth factor I gene expression and serun level by a somatostatin analogue. 1994. doi:10.1006/bbrc.1994.2175
[7] Huynh H, TETENES E, WALLACE L. In Vivo inhibition of insulin-like growth factor gene expression by tamoxifen, 1993
[8] GUVAKOVA M A, SURMACZ E. Tamoxifen interferes with the insulin-like growth factor Ⅰ receptor (IGF-IR) signaling pathway in breast cancer cells, 1997
[9] WALSH M P. Calmoduhn and the regulation of smooth muscle contraction. 1994. doi:10.1007/BF00925958
[10] SZUCS G, HEINKE S, de GREEF C. The volume-activated chloride current in endothelial cells from bovine pulmonary artery is not modulated by phosphorylation, 1996
[11] NILIUS B, PRENEN J, SZUCS G. Calcium-activated chloride channels in bovine pulmonary artery endothelial cells, 1997

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