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氢氯噻嗪的利尿与抗利尿作用致大鼠尿量及组织含水量的变化

作者:时间:2011-02-11 10:28:34 来源:www.ksfbw.com 阅读次数:920次 ]

【摘要】　　目的：探讨药物氢氯噻嗪对健康机体的利尿作用与抗利尿作用间的规律关系。方法：对应用氢氯噻嗪健康大鼠组和无药对照鼠组，分别采用自由饮水、少量清水灌胃（4h:125mL·kg-1)、和较大量清水灌胃（4h:175mL·kg-1)及超量清水灌胃（4h:260mL·kg-1)的“清水利尿”条件时，观察给水量不同条件时大鼠6h尿量的变化，及超量水灌胃后大鼠血浆渗透压、脑组织含水量及肾组织病理切片水肿情况。结果：自由饮水和少量水灌胃条件时，用药鼠的6h尿量多于未用药鼠（P＜0.01）；在较多水灌胃和超量水灌胃条件时，用药鼠的6h尿量少于未用药鼠（P＜0.01）；在超量水灌胃（4h:260mL·kg-1)后，用药鼠血浆渗透压比未用药鼠低，而用药鼠脑组织含水量比未用药组鼠多（P＜0.01），用药组鼠肾组织病理切片出现明显的水肿，未用药组鼠无明显水肿。结论：氢氯噻嗪本身具有利尿作用与抗利尿作用并存，即当尿量不多时显现出利尿效应，当尿量过多（如水利尿）时显现出抗利尿效应；且若进入机体水量过多，该药可致水中毒。

【关键词】氢氯噻嗪；抗利尿作用；水中毒；血浆渗透压；脑组织含水量

　　［ABSTRACT］ Objective: To explore diuretic and relative antidiuretic effect of hydrochlorothiazide on various water intake patterns. Methods: Rats were randomly divided into hydrochlorothiazide administration group (group A) and nonadministration group (group B). Two rats were raised in one metabolic cage, and six cages were comprised in each group. Free water intake (feeding, p.o.), controlled water intake with low volume (intragastric administration with 125 mL/kg in 4hrs, i.g.125), medium volume (175 mL/kg in 4 hrs, i.g.175) and excessive water intake (260 mL/kg in 4 hrs, i.g.260) were employed to each group( group A and B, respectively). In first round, quantities of urine volume in the first 6 hrs (Vol6), plasma osmolality (Posmol) and cerebral tissue content of water (CH2O) were calculated by hydrochlorothiazide administration for 3 days (or placebo) in groups. Controlled water intake with i.g.175 and i.g.260 were employed in the second and the third round in group A and B, Vol6 and CH2O were calculated, respectively. Results: A significantly high urine volumes in the first 6 hrs were observed in group A (P＜0.01) from p.o. and i.g.125 rats, but significantly low in i.g.175 and i.g.260 rats (P＜0.01). It showed the lower plasma osmolality level in group A i.g.260 rats, while the cerebral tissue content of water were significantly high (P＜0.01). A clearly histological edema changes could be found in group A i.g.260 rats. Conclusions: Hydrochlorothiazide has diuretic and antidiuretic effects. Functional shift from diuresis to antidiuresis is depending on urine formation, which means diuretic effect combined with low urine formation, while antidiuresis effect combines with high urine formation. It is demonstrated that hydrochlorothiazide administration has the risk to water intoxication under the excessive water intake condition.

　　［KEY WORDS］ Hydrochlorothiazide; Antidiuretic effect; Water intoxication; Plasma osmotic pressure；Brain water content

　　氢氯噻嗪（hydrochlorothiazide HCTZ）是经典的排钠利尿药，该药作用与机制早已明确，但HCTZ又能够使尿崩症者的尿量减少，是治疗肾性尿崩症的首选有效药。但是对健康机体，迄今尚缺资料显示该药又使尿量增多（利尿）同时又使尿量减少（抗利尿）的两种相反效应［1］。因而该药使尿崩症者的尿量减少的主要机制，通常认为由该药的排钠作用致尿崩症者体液渗透压下降——患者渴感消失而饮水减少——尿量减少［2］。本研究试图通过氢氯噻嗪影响健康大鼠，分别在自由饮水、少量被动清水灌胃和较大量及超量清水灌胃的“水利尿”［3］条件时，观察鼠排尿量及其组织含水量的变化，以探明该药本身是否具有抗利尿的药理作用，以及其利尿和抗利尿的作用规律。

　　1 材料与方法

　　1.1 材料

　　1.1.1 主要材料

　　氢氯噻嗪片(山西利丰华瑞制药有限责任公司生产，批号20080507)，注射用水溶解后灌胃；双蒸水（自制；用作大量灌胃造成水利尿）；清洁级SD雄性大鼠，200～250g（购自中山大学实验动物中心）。

教育核心期刊论文发表　　

　 1.1.2 实验设备

大白鼠代谢笼［4］、冰点渗透压计(Beokman Coulter Lx．USA)、电热恒温箱、万分之一电子分析天平、普通电子秤。

　　1.2 方法

　　1.2.1 筛选与分组

　　将大鼠自由饮水，禁食18h后，38℃双蒸水，25mL·kg-1灌胃，装进大鼠代谢笼收集2h尿量，尿量达灌水量40%以上者入选［4］；随机分成A、B组，每组各12只。A组氢氯噻嗪溶液灌胃给药，25mg·kg－1·d－1，分2次，连续7d。B组不给药。非收集尿量期间两组均自由饮水，不禁食。

　　1.2.2 收集尿量

　　分别将同组2鼠放入1个代谢笼，均收集6h尿