氢氯噻嗪对大鼠的利尿作用的研究

目的：探讨氢氯噻嗪对大鼠的利尿作用及其作用机制。方法：选取20只自发性血压高大鼠（SHR）,其中10只采用灌胃针给予氢氯噻嗪灌胃,10mg/kg,设为A组;另外10只给予相同剂量的生理盐水灌胃,设为B组;持续4周。比较两组大鼠灌胃4周内的血压变化,24h尿量变化以及血管紧张素Ⅱ1型受体（AT1）及细胞色素P450（CYP）表氧化酶2C11基因表达的情况。结果：氢氯噻嗪可显著降低SHR大鼠的血压,A组4周内的血压变化显著大于B组（P〈0.05）。A组大鼠2周、4周的24h尿量显著高于B组（P〈0.05）。且A组大鼠心脏、肾脏、肝脏中的AT1mRNA的下调水平,CYP表氧化酶2C11mRNA的上调水平的幅度显著大于B组（P〈0.05）。结论：氢氯噻嗪可能通过下调AT1和上调CYP表氧化酶2C11水平可能与其引起SHR强利尿效果有关,以降低血压和保护器官。

A RESEARCH OF DIURETIC EFFECT ON HYDROCHLOROTHIAZIDE IN RATS

Objective：To investigate the diuretic effect of hydrochlorothiazide in rats and its mechanism of action. Methods：20 spontaneous blood pressure in hypertensive rats （SHR） were selected, hydrochlorothiazide was given into stomach by gavage needle in 10 rats, 10mg / kg, which was set to group A; the other 10 rats were given the same dose of saline, set to group B, for 4 weeks. Two groups of rats were compared by the changes in blood pressure, 24h changes in urine volume and the gene expression of angiotensin II type 1 receptor （AT1） and cytochrome P450 （CYP） table oxidase 2C11, for 4 weeks. Results： hydrochlorothiazide can significantly reduce the blood pressure of SHR rats; the variation of the blood pressure within 4 weeks in group A was greater than that in group B （P 0.05）. 24h urine volume of 2 weeks and 4 weeks in group A was significantly higher than that in group B （P 0.05）. And AT1 mRNA down-regulated level, CYP oxidase 2C11 mRNA up-regulated level of amplitude in the heart, kidney and liver of group A was greater than that in group B （P 0.05）. Conclusion：hydrochlorothiazide could down-regulate level of AT1 and up regulate level of CYP enzyme 2C11; so that might cause strong diuretic effect of SHR, to lower blood pressure and organ protection.