重组生长激素与谷氨酰胺协同促进短肠大鼠小肠的代偿

目的　研究添加生长激素(rhGH)及谷氨酰胺(Gln)的肠外营养(PN)对短肠大鼠残存小肠代偿的作用及机制。方法　按2×2析因实验方案，将SD大鼠随机分成STD、Gln、rhGH及rhGH+Gln组，建立PN短肠动物模型。PN6d后行小肠黏膜形态学检查，并行细胞增殖核心抗原(PCNA)测定、原位末端标记(TUNEL)染色及胰岛素样生长因子-1(IGF-1)mRNA的Northernb1ot测定。结果　rhGH+Gln组残余小肠黏膜形态学上呈显著代偿表现。析因分析表明，rhGH与Gln间存在协同作用(P＜0.01)。其PCNA表达显著高于rhGH、Gln与STD组，分别为24.95±3.93、19.28±3.25、17.27±3.38与8.37±2.23(P＜0.01)；凋亡指数显著降低，分别为5.68±2.07、8.06±2.33、10.00±2.24及22.32±3.84(P＜0.01)；小肠IGF-1mRNA表达在rhGH+Gln组显著高于rhGH、Gln及STD组，分别为0.73±0.05、0.62±0.04、0.51±0.04及0.41±0.22(P＜0.05)。结论　rhGH与Gln通过促进肠黏膜上皮细胞增生与抑制其凋亡，协同促进短肠大鼠残存小肠代偿，小肠IGF-1在二者协同作用的发挥中起重要的介导作用。

Recombinant human growth hormone and glutamine synergistically improve the adaptation of the remnant small intestine of short bowel syndrome rats

Objective To study the effect and the underlying mechanism of glutamine (Gln) and recombinant human growth hormone (rhGH) on the adaptation of the remnant small intestine in parenterally fed, short bowel syndrome (SBS) rats. Methods Four parenteral nutrition treatment groups of SBS rats were randomly arranged in a 2×2 factorial design as follows: STD group (-rhGH, -Gln), Gln group(-rhGH, +Gln), rhGH group( + rhGH,-Gln) and rhGH + Gln group ( + rhGH, + Gln). The morphological changes of the intestinal mucosal epithelia were investigated, the expression of PCNA and the cells apoptosis were determined, by immunohistochemical staining and TUNEL methods. Intestinal insulin like growth foctor-1 (IGF-1) mRNA were determined by Northern blot analysis. Results Mucosal thickness, villous height, crypt depth and villous surface of the remnant small intestine in rhGH + Gin group were increased significantly compared to other experimental groups, there were synergistic effects between rhGH and Gln ( P＜0.01 ); The expression of PCNA was higher in rhGH +Gln group than in rhGH, Gln and STD group (24.95 + 3.93、 19.28+ 3.25、 17.27 + 3.38,8.37 + 2.23 respectively, P＜0.01); but the rate of apoptosis was lower in rhGH+ Gln group than in rhGH, Gln and STD group (5.68 + 2.07、8.06 + 2.33、10.00 + 2.24,22.32 + 3.84 respectively, P ＜0.01); The expression of the intestinal IGF-1 mRNA was also higher in rhGH + Gln group than in rhGH, Gln and STD group(0.73 + 0.05、0.62 + 0.04、0.51 + 0.04,0.41 + 0.22 respectively, P＜0.05).Conclusions The combination of rhGH and Gln can significantly improve the adaptation of the remnant small intestine in parenterally fed SBS rats. There are synergistic effects between them. The increase of cell proliferation and the decrease of cell apoptosis are both contribute to the adaptation. The increase of the local IGF-1 plays an important role in this process.