花生四烯酸细胞色素P450表氧化酶转基因表达对自发性高血压大鼠血压的影响及机制探讨  

Overexpression of Arachidonic Acid Cytochrome P450 Expoxygenases Decreases Blood Pressure via Negative Inotropic Effect in Spontaneous Hypertensive Rats

作　　者：肖斌[1] 周昌清[1] 李袁静[1] 熊小菊[1] 汪道文[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院高血压病研究所,武汉市430030

出　　处：《医学分子生物学杂志》2007年第5期386-390,共5页Journal of Medical Molecular Biology

基　　金：国家自然科学基金重点项目(No.30430320);国家高技术研究发展计划(863计划)(No.2004AA217060);国家教育部博士点基金(No.20040487079)~~

摘　　要：目的应用重组腺相关病毒作为基因导入的载体,将CYP450表氧化酶2J2基因导入到自发性高血压大鼠(SHR)体内,观察其对SHR血压的影响。方法15只雄性SHR随机分为3组,分别予以病毒悬浮缓冲液,rAAV-GFP和rAAV-2J2尾静脉注射(1×1012pfu/只)。用尾套法监测大鼠尾动脉血压,持续6月;实验结束前采用Millar导管检测心功能。采用Western印迹法检测目的基因在大鼠体内的表达。结果2J2组的血压从第2月开始下降,并保持相对较低的水平,而对照组则缓慢上升,两者间有显著性差异。2J2组心内最大收缩压,收缩末压,dp/dtmax和dp/dtmin的绝对值与对照组相比较均显著下降。2J2组大鼠的心搏出量和心输出量与对照组相比较显著增加。结论CYP表氧化酶及其代谢产物EETs对心肌的负性肌力调节机制可能是其调节高血压的重要机制之一。Objective To investigate the effect of overexpressing CYP epoxygense genes mediated by rAAV on blood pressure in spontaneous hypertensive rats. Methods Fifteen spontaneous hypertensive rats were randomized to 3 groups ： control, GFP, and 2J2 groups. In GFP and 2J2 groups rats were injected respectively via vena caudalis with vectors （ 1 × 10^12 pfu for each rat） while rats in the control group were given buffered vehicle. The blood pressure of arteria caudalis was measured over a period of 6 month. Before the rats were sacrificed at the 6th month, the cardiac functions were measured with a pressure-volume system. Results The systolic blood pressure in rAAV-2J2-treated group decreased from 173.0 ±2.8 mmHg to 163.5 ±5.8mmHg （P 〈0.01 ） at the 2nd month, and the pressure was 165.0 ± 4. 7 mmHg 6 months after gene injection. On the other hand, in rAAV- GFP-treated animals, the systolic blood pressure was from 174. 0 ±3.9 mmHg to 179.0 ±4. 9 mm- Hg at the 2nd month and increased to 195.2 20. 8 mmHg at the 6＇h month, about 30 mmHg higher than that in rAAV-2J2-treated group （P 〈 0. 001 ）. The maximum intra-cardiac pressure was 201.1 ±32. 8 mmHg in the 2J2-treated group, significantly lower than that of control （245.9 ± 16. 2 mm- Hg） （P 〈0.01 ）. The end-systolic pressure in the treated group was 199.0 ±33.3 mmHg, and that in the control group was 237.6 ± 14.2 mmHg. Both the dp/dtmax and the absolute value of dp/dtmin. were decreased from 17005.5 ± 1850. 8 mmHg/s and 16930. 8 ± 2080. 0 mmHg/s in control group to 16930. 8 ± 2080.0mmHg/s and 13223.4 ± 1792. 4 mmHg/s in 2J2-treated group, respectively. However, the cardiac output （CO） in the treated animals was significantly higher than that in the controls （26870. 7 ±6431.3 pJ/min vs. 19826. 1 ±2906. 0 pJ/min） （P 〈0. 05）. Conclusion Our study demonstrated that transduction of rAAV-mediated 2J2 genes decreases the blood pressure and prevents development of hypertension in SHR. CYP epoxygenase and its metabolites EETs

关 键 词：花生四烯酸 细胞色素P450表氧化酶 表氧二十碳三烯酸 重组腺相关病毒 高血压 

分 类 号：R349.6[医药卫生—基础医学]