乳铁蛋白对去卵巢大鼠骨胰岛素样生长因子-1受体及其结合蛋白-2、4 mRNA表达的影响

Effects of lactoferrin on the expressions of IGF-1R and IGFBP-2,4 mRNA in bone of ovariectomized rats

目的探讨乳铁蛋白对去卵巢大鼠骨组织中胰岛素样生长因子-1受体(insulin-like growth factor-1 receptor,IGF-1R)、胰岛素样生长因子结合蛋白-2(insulin-like growth factor binding protein-2,IGFBP-2)、胰岛素样生长因子结合蛋白-4(insulin-like growth factor binding protein-4,IGFBP-4)mRNA表达的影响。方法50只清洁级雌性SD大鼠采用数字表法随机分为去卵巢模型组(Ovx组)40只与假手术组(Sham组)10只,同时把去卵巢大鼠模型组随机分为模型组(蒸馏水2 m L/d)(Con组)、乳铁蛋白(0.1 g/kg·d)组(LF1)、乳铁蛋白(1 g/kg·d)组(LF2)、乳铁蛋白(2 g/kg·d)组(LF3),每组10只,连续干预治疗6个月后,采用实时荧光定量PCR检测各组大鼠骨组织中IGF-1R、IGFBP-2、IGFBP-4 mRNA表达的情况,分析其异同。结果 HE染色结果显示:Sham组骨小梁排列密集,细胞数量多;而Con组骨小梁排列稀疏,细胞数量少;LF组介于Sham组和Con组之间,不同的乳铁蛋白干预后,与Con组相比,随着乳铁蛋白剂量增大,其骨小梁排列密度增大,细胞数量增多。与Sham组比较,Con组大鼠骨组织中IGFBP-2、IGFBP-4 mRNA相对表达量明显增高,IGF-1R mRNA相对表达量明显降低(均P<0.01)。与Con组比较,LF1组、LF2组、LF3组大鼠骨组织中IGFBP-2 mRNA相对表达量明显下降为0.085±0.01、0.013±0.00、0.012±0.00,IGFBP-4 mRNA下降为0.329±0.07、0.040±0.01、0.032±0.01,二者下降量均与乳铁蛋白浓度正相关(均P<0.01);而IGF-1R mRNA相对表达量升高为1.977±0.55、3.139±0.53、3.600±2.46,呈剂量依赖性升高。结论乳铁蛋白可能抑制去卵巢大鼠骨组织IGFBP-2、IGFBP-4 mRNA的表达,促进其IGF-1R mRNA的表达。

Objective To investigate the impact of the lactoferrin on the gene expression of insulin-like growth factor-1 receptor （IGF-1 R）, insulin-like growth factor binding protein-2 （IGFBP-2） and insulin-like growth factor binding protein-4 （IGFBP-4） in the ovariectomized rat models. Methods Randomly divide 50 cleaning female Spra- gue-Dawley rats into two groups： 40 in Ovx group and 10 in Sham group. And the 40 rats are subdivided randomly into the following groups： the Con group （distilled water 2 mL/d） , the Lactoferrin （ 100 mg/kg· d） group （ LF1 ） , the Lactoferrin （1 g/kg · d） group （LF2）, and the Laetoferrin （2.0 g/kg· d） group （LF3）. Each group has 10 rats. Give them 6 months of interventional treatment, employ real-time PCR to measure the levels of insulin-like growth factor binding protein 2 （IGFBP-2）, the insulin-like growth factor binding protein 4 （IGFBP-4）, the insulin-like growth factor-1 receptor （IGF-1R） mRNA. Results HE Staining shows that the trabecular bone has dense arrangement with a large amount of cells in Sham group, while in the Con group, it decreases in amount with dimination and breakage, and widens in space with few and scattered cells, which leads to a relatively large empty area in its structure. Trabecular bone of group LF is between group Sham and group Con. In condition of interventions of different lactoferrins, compared with group Con, the trabecular bone in group LF increases in its dense arrangement and thickness but decreases its space. Compared with the sham-operated group, the relative expression of IGFBP-2, IGFBP-4 mRNA in the Con group significantly increases while the expression of IGF-1R mRNA significantly decreases （All P 〈 0. 01 ）. Compared with the Con group, in group LF1, LF2, and LF3, the relative expression of IGFBP-2 significantly decrease to 0. 085 ± 0. 01, 0. 013± JP ｜ 0. 00, 0. 012 ±0. 00, IGFBP-4 mRNA decrease to 0. 329±0.07, 0. 040 ±0. 01, 0. 032 ±0.01, which are positively correlated to the concentration of the lactoferrin （All P 〈 0. 01 ）. While the expression of IGF-1R mRNA significantly increase to 1. 977 ±0. 55, 3. 139 ±0. 53, 3. 600 ± 2.46 and elevates in a dose-dependent manner. Conclusion Lactoferrin can promote the expression of IGF-1R mRNA but possibly inhibit the expression of IGFBP-2 and IGFBP-4.