自发性高血压大鼠苯丙氨酸代谢动力学异常.docVIP

???? 自发性高血压大鼠苯丙氨酸代谢动力学异常? ???? ????摘　要　目的和方法：自发性高血压大鼠(SHR)及相应的正常血压对照大鼠(Wistar Kyoto大鼠，WKY)静注［3H］苯丙氨酸后的药物动力学及组织摄取。结果：苯丙氨酸在大鼠的药物动力学符合二室开放模型。与WKY相比，SHR中苯丙氨酸消除半衰期延长，清除率缩小，药时曲线下面积增加，中央室表观分布容积增加，心脏对苯丙氨酸摄取增加。结论：高血压病可能是一种与遗传性氨基酸代谢异常有关的疾病。　　主题词　苯丙氨酸；高血压；大鼠；药代动力学 Abnormal pharmacokinetics of phenylalanine in spontaneously hypertensive rat GU Tian-Hua, ZHAO Guang-Sheng, ZHANG Zhao-Ying, PAN Wei-HuaShanghai Institute of Hypertension, Shanghai(200025) 　　Abstract　AIM and METHODS: Pharmacokinetics and tisssure uptake of ［3H］ phenylalanine in spontaneous hypertensive rat (SHR) and the control rat-Wistar Kyoto rat (WKY) were studied. At different times after i. v. administration of phenylalanine, the radioactive counts in blood and tissures of SHR or WKY were measured with liquid scintillation counter. RESULTS: Pharmacokinetic process of phenylalanine in rats conformed to the open two compartmental model. In SHR T1/2β was 300±150 min, clearance was (0.56±0.22) mg·min-1, apparent volume of distribution was (27±13) g and area under concentration-time curve was (8300±3600) counts·min-1·mg-1. The corresponding values in WKY were 110±50,1.40±0.60,13±3 and 4200±2000, respectively. The differences of these values between SHR and WKY were statisically significant (P＜0.01). In SHR the uptake of phenylalanine by heart was (72±29)counts·min-1·mg-1 at 2 h after i v administration, which was higher than that in WKY (33±12)counts·min-1·mg-1,P＜0.01. CONCLUSION: Hypertension probably belongs to the category related to inherited amino acid metabolic aberration.　　MeSH　Phenylalanine; Hypertension; Rats; Pharmacokinetics 　　我们过去在动物及人的实验中先后证明血清苯丙氨酸与血压呈负相关［1］，在双亲均患高血压的正常血压子女中存在有苯丙氨酸代谢动力学障碍［2］，而断奶的自发性高血压大鼠(spontaneously hypertensive rat, SHR)喂富含苯丙氨酸的饲料能显著减慢其血压随年龄上升的速度［3，4］。因此我们曾提出“高血压病可能是与遗传性氨基酸代谢异常有关的疾患”的假设［2］。本文以SHR为主要研究对象，测定一次静注苯丙氨酸后其药物动力学变化规律及组织对苯丙氨酸的摄取。通过与其相应的正常血压对照大鼠Wistar京都种大鼠(WKY)进行比较，以探讨在SHR这种以遗传性高血压为特征的高血压大鼠模型中苯丙氨酸的代谢特点，并进一步验证上述假设的正确性及可靠性。 材料与方法　　1.动物：SHR及WKY各10只，雌、雄各半，鼠龄3～4月，体重SHR雄性为(26