神经肽Y在L-NAME致孕鼠高血压中的作用

Effect of Neuropeptide Y on Hypertension Induced by L-NAME in Pregnant Rats

目的研究神经肽Y(NPY)在一氧化氮(NO)合酶抑制剂亚硝基左旋精氨酸甲酯(L-NAME)致孕鼠高血压中的变化与作用。方法妊娠大鼠随机分为L-NAME组1、L-NAME组2、生理盐水组1、生理盐水组2(上述4组用于不同时间点的NPY含量检测)、NPY抗血清组、无抗体血清组和正常妊娠组(上述3组用于不同时间点的动脉血压观察),每组各6只。通过腹腔注射L-NAME形成晚期妊娠大鼠高血压,应用放射免疫分析法测定血浆和部分脑区NPY免疫活性物质(ir-NPY)含量的变化;通过静脉注射NPY抗血清(每只5μL,3次)观察其对孕鼠平均动脉压的影响。结果给予L-NAME后孕鼠平均动脉压显著升高;与注射等量生理盐水的孕鼠相比,L-NAME高血压孕鼠血浆ir-NPY的含量于妊娠后d21,下丘脑的含量于妊娠后d21、分娩后d2,延髓的含量于妊娠后d21均显著升高。静脉给予NPY抗血清后,L-NAME高血压孕鼠平均动脉压显著低于无抗体血清组,但仍显著高于正常妊娠组。结论外周与中枢NPY同时参与L-NAME致孕鼠高血压的病理生理过程,其水平的升高是形成和维持孕鼠高血压的因素之一。

Objective The present work aims at the effect of neuropeptide Y（NPY） on hypertension induced by nitrioxide synthase inhibitor N（G）-nitro-L-arginine-methyl-ester（L-NAME） in hypertensive pregnant rats.Methods Pregnant rats were randomly grouped as L-NAME1,L-NAME2,normal saline1,normal saline2（for NPY content assay at different time points）,anti-NPY serum,normal serum and normal pregnancy（for arterial blood pressure test）（n=6）.Immunoreactive NPY was tested by radioimmunoassay in plasma,hypothalamus and medulla oblongata in hypertensive pregnant rats prepared by intraperitoneal administration of L-NAME（27.5 mg/0.2 mL each rat） or vehicle daily from d17 of gestation till sacrifice.Non-pregnant rats served as basal control.Systolic arterial pressure was measured by the tail cuff method daily from d16 of gestation till d2 post partum.Effect of NPY on blood pressure was investigated by intravenous injection of anti-NPY serum or guinea pig serum with absence of NPY antibody.Results Compared with those of the normal pregnant rats,levels of immunoreactive NPY were significantly higher in plasma at d21 of gestation,in hypothalamus at d21 of gestation and d2 post partum,and in medulla oblongata at d21 of gestation.Arterial pressure of the pregnant rats administered with L-NAME followed by anti-NPY serum was significantly lower than those administered with L-NAME followed by guinea pig serum,whereas significantly higher than those of the normal pregnant group.Conclusions Both peripheral and central NPY play some roles in pathophysiological process of hypertension in the hypertensive pregnant rats induced by L-NAME.Increased NPY is one of the factors that are responsible for the occurrence and development of hypertension.