中枢肾素血管紧张素系统的激活在孕期糖尿病致子代高血压大鼠中的作用  

Effects of activation of the central renin angiotensin system on the hypertension of the offspring rats induced by prenatal diabetes

作　　者：李晓龙[1,2] 罗浩[2] 陈硕[1] 王甲良[2] 李美香[2] 余俊逸[2] 曾春雨[2] 

机构地区：[1]汕头大学医学院附属第一医院心血管内科,广东汕头515041 [2]第三军医大学大坪医院心血管内科,重庆市心血管病研究所

出　　处：《中华高血压杂志》2016年第2期147-151,共5页Chinese Journal of Hypertension

基　　金：国家自然科学基金项目(31500931)

摘　　要：目的探讨中枢肾素血管紧张素系统(RAS)的激活在孕期糖尿病致子代高血压大鼠中的作用。方法Sprague Dawley大鼠随机分为链脲佐菌素组[孕期第0天(雌鼠与雄鼠交配后见阴栓当天为孕期第0天)腹腔注射链脲佐菌素35mg/kg]和对照组(注射等体积的0.9%生理盐水),每组8只;子代大鼠出生后,分别从2组中选取6只子代成年雄性大鼠进行实验。子代大鼠8周龄时,每2周采用鼠尾动脉无创血压测量法持续监测血压;子代大鼠24周龄时,取子代大鼠下丘脑室旁核,观察mRNA、蛋白表达量的改变;测定下丘脑室旁核氧化应激指标的改变。结果 12、14、16、18、20、22、24周龄时,链脲佐菌素组子代大鼠平均动脉压高于同龄期对照组子代大鼠[(97±4)比(89±3),(102±5)比(92±3),(108±2)比(94±2),(112±2)比(97±3),(115±3)比(100±3),(120±4)比(102±3),(127±3)比(103±4)mm Hg,均P<0.05]。与对照组子代大鼠相比较,链脲佐菌素组子代大鼠丙二醛明显升高,而超氧化物歧化酶明显下降(均P<0.05)。链脲佐菌素组子代大鼠下丘脑室旁核的mRNA、蛋白表达量明显高于对照组的子代大鼠(均P<0.05)。结论孕期糖尿病引起成年子代大鼠血压升高,其机制可能是氧化应激水平升高引起下丘脑室旁核血压调控中枢的RAS过度激活,最终引起成年子代大鼠高血压的发生。Objective To investigate the effects of activation of the central renin angiotensin system（RAS）on the hypertension of the offspring rats induced by gestational diabetes. Methods The Sprague Dawley（SD）rats were randomly divided into streptozotocin（STZ）group and control group. Rats in STZ group were treated with a single intraperitoneal injection of STZ（35mg/kg）to induce diabetes mellitus on the first day（day 0）of pregnancy,indicated by the presence of vaginal plug after the female SD rats mate with males,And rats in control group are injected with equal volume of 0.9% saline（n=8）. Six offspring rats in each group were randomly selected after birth.When the age of 8week,Blood pressure of the offspring rats was monitored noninvasively and continuously every 2weeks. The mRNA and protein expression of the RAS component including angiotensin converting enzyme（ACE）and angiotensin Ⅱtype 1receptor（AT1R）,as well as the oxidative stress index were determined in hypothalamic paraventricular nucleus of 24-week-old offsprings. Results At the age of 12,14,16,18,20,22,24 weeks,the mean arterial pressure of offspring rats in STZ group was higher than that in age-matched control group rats[（97±4）vs（89±3）,（102±5）vs（92±3）,（108±2）vs（94±2）,（112±2）vs（97±3）,（115±3）vs（100±3）,（120±4）vs（102±3）,（127±3）vs（103±4）mm Hg,all P〈0.05]. Compared with the control group,the levels of malondialdehyde in the STZ group increased significantly,while superoxide dismutase was markedly decreased（all P〈0.05）.Additionally,the mRNA and protein expression of ACE and AT1 R in hypothalamic paraventricular nucleus of STZ group were significantly higher than those in control group. Conclusion Maternal diabetes mellitus induced hypertension in its offspring. The mechanism may be related to the excessive activation of the central RAS in hypothalamic paraventricular nucleus due to oxidative stress.

关 键 词：孕期 糖尿病 子代 平均动脉压 下丘脑室旁核 血管紧张素转换酶 血管紧张素Ⅱ1型受体 

分 类 号：R544.1[医药卫生—心血管疾病]