摘要
目的 检测DOCA盐高血压大鼠模型主动脉上,Ⅰ型GTP环化水解酶及其反馈调节蛋白的合成及活性改变,并探讨其对四氢生物喋呤 内皮一氧化氮合成酶(BH4 eNOS)系统生成一氧化氮过程的影响。方法 以DOCA盐高血压大鼠模型主动脉组织为标本,以Griess试剂测定亚硝酸盐浓度的方法检测NO的水平;采用Westernblot检测eNOS蛋白表达水平;应用高效液相色谱法(HPLC)测定BH4 水平和GTPCH 1活性;并通过RT PCR检测GFRP和GTPCH 1的mRNA表达水平。结果 与对照大鼠相比较,在DOCA盐高血压大鼠的主动脉上,NO水平明显下降,eNOS蛋白表达水平和BH4 水平明显降低,GTPCH 1活性及mRNA表达水平显著下降,而GFRP的mRNA表达水平明显增高。结论 GTPCH 1的合成减少、活性降低,及其活性负调节蛋白GFRP表达增加,可能对DOCA盐高血压大鼠主动脉血管BH4 合成减少、eNOS活性下降及NO水平降低起关键作用。而该机制可能是导致高血压患者动脉血管功能损伤的一个重要原因。
Objective To determine GTPCH-1 and GFRP mRNA expression levels and activity variation in DOCA-salt hypertension rats and to investigate the relationship to the reduction of NO synthesis. Methods With the aorta samples from DOCA-salt hypertension rats, the NO levels were examined by nitrite detecting with Griess reagents, endothelial NO synthase (eNOS) protein expression by Western blotting, BH 4 levels and GTPCH-1 activities by HPLC and mRNA levels of GFRP and GTPCH-1 by RT-PCR. Results Comparing with sham rats, NO levels and eNOS protein were significantly reduced in aorta of DOCA-salt hypertension rats, while the BH 4 level was markedly decreased. GTPCH-1 activities and mRNA expression levels declined significantly, whereas GFRP mRNA levels were markedly increased. Conclusion The decrease in GTPCH-1 expression levels and activities, and the abnormally increased GFRP level directly diminish the synthesis of BH 4, then indirectly down-regulate the activities of eNOS, finally impair NO levels in aorta of DOCA-salt hypertension rat model. This mechanism may play an important role in the development of vessel dysfunction in hypertension patients.
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2005年第8期745-748,共4页
Journal of Third Military Medical University
