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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 role of central renin-angiotensin system (RAS) in the generation of hypertensive rats with diabetes mellitus during pregnancy. Methods Sprague Dawley rats were randomly divided into streptozotocin group (intraperitoneal injection of streptozotocin 35mg / kg on day 0 of pregnancy (day of vaginal suppository after female and male rats mating), and control The rats were injected with equal volume of 0.9% saline, and each group had 8 rats. After the offspring were born, six male offspring were selected from the two groups to conduct experiments. At 8 weeks of age, the offspring rats were monitored for blood pressure every 2 weeks by noninvasive blood pressure measurement of the caudal artery. When offspring were 24 weeks old, the hypothalamic paraventricular nucleus of the offspring rats was taken for observation of mRNA and protein expression Changes in the hypothalamic paraventricular nucleus oxidative stress indicators. Results At 12, 14, 16, 18, 20, 22 and 24 weeks of age, the average arterial pressure of the offspring rats in the streptozotocin group was significantly higher than that in the offspring of the same age [(97 ± 4) vs (92 ± 3), (108 ± 2), (94 ± 2), (112 ± 2), (97 ± 3), (115 ± 3), (100 ± 3) ), (120 ± 4) vs (102 ± 3), (127 ± 3) vs (103 ± 4) mm Hg, all P <0.05]. Compared with the offspring rats in the control group, the serum malondialdehyde (MDA) and the superoxide dismutase (SOD) in the offspring of streptozotocin group were significantly decreased (all P <0.05). The mRNA and protein expression of hypothalamic paraventricular nucleus of rats in streptozotocin group were significantly higher than those in the control group (all P <0.05). Conclusions Diabetes mellitus in pregnancy may cause hypertension in adult offsprings. The mechanism may be that over-activation of RAS in the hypothalamic paraventricular nucleus blood pressure control center may lead to the development of hypertension in adult offsprings.