精氨酸加压素V2受体拮抗剂对阿霉素肾病大鼠肾脏水通道蛋白的影响

Effects of arginine vasopressin V2 receptor antagonist on renal aquaporins of adriamycin-induced nephropathy rats

目的 探讨精氨酸加压素V2受体 (AVPV2R)拮抗剂对阿霉素肾病大鼠肾脏水通道蛋白的影响。方法 2 4只大鼠分为正常对照组 (NC组 )、阿霉素肾病未治疗组 (NS组 ) ,阿霉素肾病 +AVPV2R拮抗剂干预组 (NS V组 )和阿霉素肾病 +福辛普利干预组 (NS F组 ) ,每组各 6只。在第 4周末 ,检测各组大鼠血、尿钠及渗透压等 ,同时检测大鼠肾脏AQP2、AQP3、AVPV2R的mRNA和蛋白表达情况。结果 ①阿霉素大鼠在 4周末时有明显的高血钠和高血渗透压 ,同时伴低尿钠和低尿渗透压 ,而AVPV2R拮抗剂和福辛普利均能降低血钠 ,改善高血渗透压 ,AVPV2R拮抗剂还显著提高尿渗透压和尿钠。②与NC组相比 ,NS组大鼠肾脏AVPV2R表达明显下调 ,AVPV2R拮抗剂则使其进一步下调。③AVPV2R拮抗剂能上调阿霉素肾病大鼠肾脏AQP2mR NA的表达 ,同时降低肾脏AQP2蛋白表达。而福辛普利和AVPV2R拮抗剂均能减少肾脏AQP3mRNA和蛋白表达。结论 AVPV2R拮抗剂能改善阿霉素肾病大鼠的水钠潴留状态 。

Objective To observe the effects of arginine vasopressin V2 receptor (AVP V2R) antagonist on water and sodium retention of adriamycin-induced nephropathy rats and to explore its mechanism. Methods Nephropathy was induced by intravenous injection of ADR. The rats were divided into 4 groups: untreated adriamycin nephropathy group(NS group), Adriamycin nephropathy group treated by AVP-V2R antagonist (V group, 42 μg·kg -1·d -1, by subcutaneous injection), Adriamycin nephrotic group treated by fosinopril (F group, 25 mg·kg -1·d -1 by gavage) and normal control group (NC group). The interventions continued for 4 weeks. Plasma sodium, osmolality, urinary osmolality and urinary sodium excretion were measured at the end of the study. Immunohistochemistry and Western Blot were used to detect the expression of AQP2, AQP3 and AVP V2 receptor in the kidney. RT-PCR was used to examine the AQP2 mRNA, AQP3 mRNA and AVP V2 receptor in the kidney. Results ①Increased plasma osmolality and plasma sodium in nephropathy rats were ameliorated and urinary osmolality and urinary sodium excretion were increased by AVP V2R antagonist. ②AVP V2R antagonist decreased the expression of AVP V2R protein in the kidney. ③Compared with the untreated NS rats, the expression of AQP2 mRNA in the kidney increased and the expression of AQP2 protein in the kidney decreased in AVP-V2R antagonist treated rats. At the same time, compared with the untreated nephropathy rat, the expression of APQ3 decreased in AVP V2R antagonist treated rats. Conclusion AVP V2R antagonist mitigates water and sodium retention of Adriamycin nephropathy rats by changing the expression of AQP2 and AQP3 in the kidney.