DAla2GIP对淀粉样前体蛋白/早老素1转基因小鼠膝关节软骨损伤保护效应的研究  

Experimental study on the therapeutic effect of DAIa2GIP on knee articular cartilage injury in amyloid precursor protein/presenilin 1 mice

作　　者：吴松[1] 石俊俊[1] 卫定禄 李盛春[1] 王宇泽[1] 

机构地区：[1]山西医科大学第二医院骨科骨与软组织损伤修复山西省重点实验室,太原030001

出　　处：《中华实验外科杂志》2017年第11期1861-1864,共4页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金（31200728、31300802）;山西医科大学第二医院博士启动基金（20120408、20120407）

摘　　要：目的探讨葡萄糖依赖性肠促胰岛素多肽（GIP）类似物DAla2GIP对淀粉样前体蛋白/早老素1（APP/PS1）转基因小鼠膝关节软骨损伤的保护效应及潜在机制。方法雄性APP/PS1小鼠及同窝出生野生型小鼠随机分为4组（6只/组）进行实验研究。结果免疫组织化学、免疫荧光和酶联免疫吸附试验（ELISA）结果显示，与野生型对照组比较，转基因组小鼠膝关节软骨肿瘤坏死因子-α（TNF-α，0.11±0.02，P＝0.001）和基质金属蛋白酶（MMP）-13（0.20±0.04，P＝0.001）表达量，脑组织及血浆中TNF-α[（331.60±39.06） pg/ml，P＝0.018]和MMP-9[（98.56±3.08） pg/ml，P＝0.001]及脑组织胶质纤维酸性蛋白（GFAP，0.74±0.12，P＝0.001）含量显著增高，而Ⅱ型胶原（ColⅡ，0.05±0.01）表达量显著下降（P＝0.002）；而经DAla2GIP治疗后，基本逆转转基因对照组的改变。结论APP/PS1转基因小鼠可能是通过促进TNF-α、MMP-9和MMP-13等炎症因子的分泌而诱发骨性关节炎的发生；而DAla2GIP可以通过抑制炎性因子对软骨细胞的损伤来发挥保护效应。Objective To observe the protective effects and potential mechanism of glucose - de- pendent- insulinotropic polypeptide （GIP） analogue DAla2GIP on knee cartilage damage of amyloid pre- cursor protein/presenilin 1 （APP/PS1） mice. Methods Male APP/PS1 mice and the littermate wild - type mice were randomly divided into four groups （6/group） to experiment. Results The immunohisto- chemistry, immunofluorescence and enzyme linked immunosorhent assay （ELISA） revealed： Compared with the WT -PBS group, the level of tumor necrosis factor （TNF） -α （0. 11± 0. 02 ） and matrix metal- loproteinase （MMP） - 13 （0. 20 ± 0. 04 ） in articular cartilage of APP/PS1 group were significantly higher （P=0.001）, whereas, the expression of type Ⅱ collagen （Col Ⅱ, 0.05±0.01） was lower （P= 0.002）, the values of TNF - ct （331.6 ± 39. 06） pg/ml, P= 0.018], MMP - 9 [（98.56 ± 3.08） pg/ml, P =0. 001] and glial fibrillary acidic protein （ GFAP,0. 74 ± 0. 12, P = 0. 001 ） in brain tissue and plasma of APP/PS1 group were significantly higher. But treatment with DAla2GIP reversed the changing in transgenic mice. Conclusion The increased secretion of inflammatory eytokines may lead to the injury of articular cartilage in APP/PS1 transgenic mice. DAla2GIP may protect the articular cartilage damage by reduce the secretion of inflammatory cytokines and increase the expression of Col Ⅱ , which may open up new ways for clinical treatment of osteoarthritis.

关 键 词：淀粉样前体蛋白/早老素1转基因小鼠 骨性关节炎 葡萄糖依赖性肠促胰岛素多肽类似物 炎性因子 

分 类 号：R684.3[医药卫生—骨科学] R749.16[医药卫生—外科学]