肾病综合征大鼠精氨酸血管加压素和V_2受体与水孔蛋白-2的研究及黄芪的治疗作用

EFFECTS OF ASTRAGALUS MEMBRANACEUS ON mRNA EXPRESSIONS OF VASOPRESSIN(AVP),V2 RECEPTOR,AQP 2 IN RATS WITH ADRIAMYCIN INDUCED NEPHROTIC SYNDROME

目的：研究下丘脑精氨酸血管加压素（ Ａ Ｖ Ｐ） 和其 Ｖ２ 受体与 Ａ Ｖ Ｐ 依赖性水通道水孔蛋白２（ Ａ Ｑ Ｐ２ ）在阿霉素肾病综合征大鼠肾脏表达的情况，及中药黄芪对此的影响。 方法：下丘脑 Ａ Ｖ Ｐ ｍ Ｒ Ｎ Ａ 检测用斑点杂交法，肾脏皮髓质 Ａ Ｖ Ｐ Ｖ２ 受体、 Ａ Ｑ Ｐ２ ｍ Ｒ Ｎ Ａ 检测采用半定量 Ｒ Ｔ Ｐ Ｃ Ｒ 法。 结果：肾病大鼠下丘脑 Ａ Ｖ Ｐｍ Ｒ Ｎ Ａ表达较正常对照增强（ Ａ：５３５９ ±５４９ ｖｓ ２５７２ ±１９６ ， Ｐ＜ ００１） ，黄芪可纠正此种高表达（ Ａ：２１８８ ±１２５） 。半定量 Ｒ Ｔ Ｐ Ｃ Ｒ 检查发现肾脏皮质和髓质 Ｖ２ 受体、 Ａ Ｑ Ｐ２ ｍ Ｒ Ｎ Ａ 表达均呈现有意义的上调，黄芪则可使这些变化缓解（ Ｐ 均＜ ００１） 。 结论：在阿霉素肾病大鼠中存在下丘脑 Ａ Ｖ Ｐ 基因表达的增加，肾脏 Ａ Ｖ Ｐ Ｖ２ 受体和 Ａ Ｑ Ｐ２ｍ Ｒ Ｎ Ａ 表达的上调，这些变化可能是肾病水潴留的机制之一，中药黄芪能改善这些变化。

OBJECTIVE To investigate the effects of Chinese herb astragalus membranaceus(AM)on mRNA expressions of hypothalamic vasopressin(AVP),renal AVP V2 receptor,and AVP dependent AQP2 in rats with adriamycin induced nephrotic syndrome. METHODOLOGY Male SD rats were randomly grouped into untreated adriamycin induced nephrotic group(NS group),AM treated adriamycin induced nephrotic group(NS+AM group)and normal control group(NC group).Rats in NS+AM group received 0 5g/(kg·day) of AM peritoneally for 4 weeks before sacrifice,while rats in other groups received normal solution in a same way.Hypothalamic AVP mRNA expression was examined by dot hybridization assay.RT PCR was applied for detection of the renal mRNA expression of V2 receptor and AQP2.The readings of the RT PCR were normalized by GAPDH mRNA in the same sample. RESULTS All rats receiving adriamycin presented typical nephrosis.No significant difference in plasma osmolarity was detected among NS,NS+AM and NC rats.Hypothalamic AVP mRNA expression was higher in NS rats than in NC rats(53 59±5 49 vs .25 72±1 96, P <0 01).AM completely reversed this up regulated expression(21 88±1 25).Both in cortex and medulla of the kidney,AVP V2 expression was found increased by 169% and 55% respectively in nephrotic rats,as compared to those in NC rats.The increment of AQP2 mRNA expression in NS rats was in consistence with that of V2 receptor.AM partially reversed the up regulated expression of V2 and AQP2 mRNA. CONCLUSION The up regulated mRNA expressions of hypothalamic AVP,renal V2 receptor and AQP 2 might play a role in edema formation in adriamycin induced nephrotic rats.AM exerts its therapeutic effects on nephrosis partially through this mechanism.