阿霉素肾病大鼠肌肉和静脉注射心钠素基因利尿作用的比较研究

Comparative Analysis of Diuretic Activities of Human ANP Gene Injected Intramuscularly and Intravenously in Adriamycin-induced Nephrotic Rats

为探讨心钠素基因经体细胞转移对阿霉素诱导的肾病动物泌尿功能的影响及其治疗肾病的潜力 ,采用肌肉或静脉内直接注射裸DNA的方法 ,将人心钠素基因的逆转录病毒载体分别导入阿霉素肾病动物体内 ,以期为其提供持续性的心钠素来源。结果发现 ,人心钠素基因经肌肉和静脉内直接注射这 2种途径导入后 ,均可使阿霉素肾病动物的尿量 体重比明显增加 ,有效利尿作用时间大于 15d。试验期间 ,实验组肾病动物的体重明显增长 ,血浆中的心钠素浓度在基因转移 5d后明显升高 ,但动物尿中的K+和Na+浓度无明显变化。以上结果说明 ,心钠素基因经肌肉和静脉 2种途径导入均可明显改善肾病动物的泌尿功能 。

In order to explore the feasibility of gene therapy strategy based on the human atrial natriuretic peptide (hANP) gene delivery for the treatment of nephropathy and compare the diuretic activities of the hANP gene injected intramuscularly(im) and intravenously(iv), the naked retroviral vector DNA harboring the hANP cDNA under the control of retroviral 5′long terminal repeat at a dose of 5 mg/kg body weight was injected im or iv into the nephrotic model rats induced with adriamycin(ADR) injected iv at a dose of 7.5 mg/kg body weight. A single injection of the hANP gene resulted in a marked elevation in plasma level of hANP 5 days after gene delivery and a significant increase in the ratio of urine volume to body weight and the diuretic effect continued for more than 15 days. In addition, there was a significant rise in the body weight of treatment groups as compared with that of negative control group and no difference in the concentrations of electrolytes in urine between groups. There was no significant differences in total effects resulted from the two routes of gene delivery and the way of gene delivery through the skeletal muscle is simpler and easier. These results suggest that somatic gene delivery of the hANP gene could enhance the renal functions in nephrotic rats significantly and would be a potential strategy for the treatment of renal disorders.