芪归合剂促进肾病综合征鼠肝IGF-Ⅰ、IGFBP-3表达的研究

Astragalus and angelica mixture could promote expressions of hepatic IGF-Ⅰ mRNA and IGFBP-3 mRNA in nephrotic rats

目的 观察芪归合剂对肾病综合征鼠 (NS鼠 )胰岛素样生长因子 Ⅰ (IGF Ⅰ )、胰岛素样生长因子结合蛋白 3 (IGFBP 3 )的作用。方法 制备大鼠阿霉素NS模型 ,设正常对照组、NS组、NS蒸馏水治疗组和NS芪归合剂治疗组 ,每组 5只大鼠。以放射免疫法和免疫放射法测定各组血、尿IGF I和IGFBP 3水平 ;用RT PCR法检测肝IGF ⅠmRNA、IGFBP 3mRNA表达 ;测量鼠的身长、体重和血生化指标。结果 NS组鼠体重增长 [( 4 7± 3 4 )g/ 4周 ]、身长增长 [( 2 6± 0 8)cm/ 4周 ]、血IGF Ⅰ [( 4 91±66) μg/L]、IGFBP 3 [( 10 2± 4 ) μg/L]低于正常鼠组 [分别为 ( 162± 19)g/ 4周、( 8 1± 1 5 )cm/ 4周、( 968±184 ) μg/L、( 13 3± 16) μg/L],尿IGF Ⅰ [( 2 64± 119)ng/ 2 4h]高于正常鼠组 [( 5 9± 16)ng/ 2 4h],而肝IGF ⅠmRNA表达 ( 0 5 2± 0 0 4 )与正常对照组 ( 0 5 3± 0 0 6)相似、IGFBP 3mRNA表达 ( 0 5 6± 0 0 5 )低于正常鼠组 ( 0 93± 0 0 5 )。芪归合剂治疗组肝IGF ⅠmRNA表达 ( 0 93± 0 0 5 )、IGFBP 3mRNA表达 ( 0 87± 0 0 5 )高于NS蒸馏水治疗组。结论 NS鼠存在IGF Ⅰ、IGFBP 3代谢紊乱和生长障碍 ,血IGF Ⅰ降低主要是由于尿中排出所致 ,而血IGFBP 3降低主要与合成减少有关。

The decrease of the serum insulin-like growth factor-Ⅰ (IGF-Ⅰ) and insulin-like growth factor binding protein-3 (IGFBP-3) was one of the main reasons of growth failure in children with nephrotic syndrome (NS). Few reports discussed how to improve growth failure in NS by promoting the synthesis of IGF-Ⅰ and IGFBP-3 and elevating serum IGF-Ⅰ and IGFBP-3 levels. Objective To study the effect of astragalus and angelica mixture on IGF-Ⅰ and IGFBP-3 in rats with nephrotic syndrome (NS).Methods Twenty male and six-week Sprague-Dawley rats weighing 155-180 g were randomly divided into four groups: control group, NS group, NS group treated with distilled water, and NS group treated with astragalus and angelica mixture. Each group contained 5 rats. Rats in NS group treated with distilled water and in NS group treated with astragalus and angelica mixture were fed with the distilled water and astragalus and angelica mixture, respectively. The dosage was 3 ml/per rat, once a day, and lasted for three weeks (21 d). Serum and urine concentrations of IGF-Ⅰ and IGFBP-3 were tested by RIA and IRMA, respectively. IGF-Ⅰ mRNA and IGFBP-3 mRNA levels in liver were detected by RT-PCR. Results The weight gain [(47±34) g/4 weeks], length gain [(2.6±0.8) cm/4weeks], serum IGF-Ⅰ [(491±66) μg/L] and IGFBP-3 [(102±4) μg/L] levels in NS group were significantly lower than those in control group [(162±19) g/4 weeks, (8.1±1.5) cm/4 weeks, (968±184) μg/L, and (133±16) μg/L, respectively]. The urine IGF-Ⅰ [(264±119) ng/24 h] level in NS group was higher than that in control group [(59±16) ng/24 h]. In NS group, the expression of IGF-Ⅰ mRNA (0.52±0.04)in the rat liver was similar to that in the control rats (0.53±0.06). While the expression of hepatic IGFBP-3 mRNA (0.56±0.05)in NS group reduced. Liver IGF-Ⅰ mRNA (0.93±0.05) and IGFBP-3 mRNA levels (0.87±0.05) in NS group treated with astragalus and angelica mixture were higher than those in NS group treated with distilled water.Conclusion Abnormal expressions of IGF-Ⅰ and IGFBP-3 and the growth failure were observed in nephrotic rats. The lower levels of the serum IGF-Ⅰ might be due to the increased urinary loss of IGF-Ⅰ. The lower levels of the serum IGFBP-3 may be caused by the decreased synthesis. Astragalus and angelica mixture could increase the hepatic expressions of IGF-Ⅰ mRNA and IGFBP-3 mRNA.