氨基酸溶液和重组人生长激素对肝硬化大鼠生长激素-胰岛素样生长因子1轴的影响

Effects of amino acid solution and recombinant human growth hormone on growth hormone/insulin like growth factor-1 axis in rats with liver cirrhosis

目的探讨氨基酸溶液和重组人生长激素(rhGH)对肝硬化大鼠生长激素(GH)胰岛素样生长因子1(IGF1)轴的影响。方法肝硬化大鼠随机分为术前组、肝部分切除后1d组、术后肠外营养用复方氨基酸注射液(Novamin)5d组、用10%复方氨基酸注射液(Hepa)5d组、用rhGH+Hepa5d组,各组均为6只大鼠,对照组为正常大鼠。分别测大鼠肝功能、血糖及血清GH、IGF-1、胰岛素样生长因子结合蛋白3(IGFBP3)水平,用逆转录聚合酶链反应检测肝白蛋白(ALB)mRNA、IGF-1mRNA、IGFBP-3mRNA的表达,肝组织行Ki67免疫组化染色。结果用Hepa的肠外营养组5d后与用Novamin组比较,GH水平明显降低,肝ALBmRNA、IGF-1mRNA、IGFBP-3mRNA表达水平明显升高,肝Ki67指数无差别;而rhGH+Hepa组肠外营养5d后比Hepa组血糖、GH、IGF-1、IGFBP-3水平明显升高,肝ALBmRNA、IGF1mRNA表达水平及肝Ki67指数也明显升高。结论氨基酸溶液和重组人生长激素均可影响肝硬化大鼠生长激素胰岛素样生长因子1轴,检测血清IGF-1、IGFBP-3水平有助于营养素的选择和评估。

Objective To explore the effects of amino acid solution and recombinant human growth hormone on growth hormone/insulin like growth factor-1 (GH/IGF-1) axis after partial hepatectomy in rats with liver cirrhosis. Methods Six normal rats severed as normal group,while 30 rats with liver cirrhosis were randomly divided into preoperation group,1 day postoperative group,8.5%Novamin PN for 5 days postoperative group,10% Hepa PN for 5 days postoperative group and rhGH+10%Hepa PN for 5 days postoperative group. Liver function,blood glucose and serum GH, IGF-1, IGFBP-3 were determined. ALB mRNA, IGF-1 mRNA and IGFBP-3 mRNA levels in liver tissues were detected by RT-PCR. Liver Ki67 immunohistochemistry staining was studied. Results Compared with the 8.5% Novamine PN group, serum ALT [(103±23) IU/L vs (154±45) IU/L], ALP[(571±92) IU/L vs (972±252) IU/L],GH[(1.55±0.12) ng/ml vs (1.81±0.11) ng/ml] level were lower(P<0.05), serum IGF-1[(966±55) ng/ml vs (813±43) ng/ml] and IGFBP-3 [(8.1±0.3) ng/ml vs (6.9±0.2) ng/ml] level and the expression of hepatic ALB mRNA (1.24±0.06 vs 1.02±0.09), IGF-1 mRNA (0.85±0.00 vs 0.60±0.03), IGFBP-3 mRNA(0.69±0.02 vs 0.58±0.09) were higher in the 10%Hepa PN group (P<0.05),but there was no difference in liver Ki67 labeling index[(4.8±0.3)% vs (4.4±0.4%)] (P>0.05). Compared with the 10%Hepa PN group, serum ALP[(434±41) IU/L vs (571±92) IU/L] was much lower(P<0.05), serum ALB[(37.0±1.8)g/L vs (32.8±1.2)g/L],blood glucose[(7.6±1.3) mmol/L vs (4.9±0.7) mmol/L],GH[(3.00±0.61) ng/ml vs (1.55±0.12) ng/ml], IGF-1[(1100±32) ng/ml vs (966±55) ng/ml], IGFBP-3[(9.3±0.2) ng/ml vs (8.1±0.3) ng/ml] level , the expression of hepatic ALB mRNA(1.35±0.04 vs 1.24±0.06),IGF-1 mRNA(0.97±0.00 vs 0.85±0.00) and liver Ki67 labeling index[(5.4±0.3)% vs (4.8±0.3%)] were higher(P<0.05) in the rhGH+10% Hepa PN group. Conclusions Amino acid solution and recombinant human growth hormone can influence the GH/IGF-1 axis in rats with liver cirrhosis . It may be helpful in selecting and evaluating nutrient by measuring the serum IGF-1 and IGFBP-3 level.