N-硝基-L-精氨酸甲酯诱导的高血压大鼠胸主动脉血管紧张素转换酶2和血管紧张素转换酶的表达

Expression of angiotensin converting enzyme 2 and angiotensin converting enzyme in thoracic aorta in hypertensive rats induced by N-Nitro-L-arginine methyl ester

目的通过观察高血压大鼠胸主动脉组织中血管紧张素转换酶(ACE)、ACE2活性及mRNA表达的改变,探讨ACE2及其与ACE相互平衡对高血压的调节作用。方法 40只血压正常且年龄匹配的SD大鼠分为模型组和对照组,每组20只。模型组大鼠每100 mL饮水中加入Nω-硝基-L-精氨酸甲酯(L-NAME)50 mg,每日摄入L-NAME 50 mg/kg,制作高血压模型;按照L-NAME的摄入时间分为第2、4、8、12周4个亚组(n=5);对照组设立相同的亚组,于相应时间分别摄入相同体积的清水。采用总活性比色法检测胸主动脉ACE和ACE2活性;RT-PCR技术检测胸主动脉ACE和ACE2 mRNA的表达。结果模型组大鼠在服用L-NAME后第4、8、12周,血压均较相应对照组显著升高(P<0.05);而对照组各亚组入组前后血压差异无统计学意义(P>0.05)。服用L-NAME后第4、8、12周,模型组大鼠的胸主动脉组织ACE活性和mRNA相对表达量均较相应对照组显著升高(P<0.05),ACE2活性及其mRNA相对表达量均较对照组显著降低(P<0.05);对照组各亚组间ACE、ACE2活性和mRNA相对表达量比较,差异均无统计学意义(P>0.05)。结论通过抑制NO合成所导致的高血压的发病过程中,胸主动脉组织ACE2、ACE的mRNA表达及活性与血压升高有关。

Objective To investigate the activity and mRNA expression of angiotensin converting enzyme（ACE） and ACE2 in thoracic aorta in hypertensive rats,and explore the role of ACE2 and ACE2/ACE in regulation of hypertension.Methods Forty age-matched SD rats with normal blood pressure were divided into model group and control group,with 20 rats in each group.Hypertension model was established in rats in model group by administration of Nω-nitro-L-arginine methyl ester（L-NAME） in drinking water（50 mg/100 mL,50 mg/kg per day）,and rats in model group were subdivided into 4 subgroups according to time of treatment（2,4,8 and 12 weeks）,with 5 rats in each subgroup.Similar subgroups were established in control group,and same amount of clear water was taken in each group at corresponding time.The activity of ACE and ACE2 in thoracic aorta was determined by high performance liquid chromatography,and the expression of ACE and ACE2 mRNA in thoracic aorta was detected by RT-PCR.Results The blood pressure of rats in model group was significantly higher than that in control group 4,8 and 12 weeks after treatment with L-NAME（P0.05）,while there was no significant change in blood pressure after intervention in each subgroup of control group（P0.05）.The activity and relative mRNA expression of ACE in thoracic aorta in model group were significantly higher than those in control group 4,8 and 12 weeks after treatment with L-NAME（P0.05）,while the activity and relative mRNA expression of ACE2 in thoracic aorta in model group were significantly lower than those in control group 4,8 and 12 weeks after treatment with L-NAME（P0.05）,and there was no significant difference in the activity and relative mRNA expression of ACE and ACE2 among subgroups of control group（P0.05）.Conclusion The activity and mRNA expression of ACE and ACE2 in thoracic aorta of rats are associated with the increase of blood pressure during the development of hypertension induced by NO synthesis inhibition.