白藜芦醇对糖尿病模型大鼠骨折愈合的影响研究

Influence of Resveratrol on the Process of Fracture Healing in Diabetic Model Rats

目的:研究白藜芦醇对糖尿病(DM)模型大鼠骨折愈合的影响。方法:尾静脉注射链脲佐菌素(60mg/kg)以复制大鼠DM模型,无菌操作下切开大鼠左侧腿部皮肤,显露左胫骨上段,线据横行锯断胫骨(胫骨平台下约0.8cm处),复位、缝合、夹板外固定,以复制大鼠DM骨折模型。实验分为4组,即正常对照(等容生理盐水)、DM骨折模型(等容生理盐水)、氟化钠(20mg/kg)与白藜芦醇(20mg/kg)组,灌胃给药,每天1次,连续8周。测定给药2、8周后的血糖、血钙、血磷、碱性磷酸酶(ALP);显微镜观察给药2、4、8周后的病理形态学变化;免疫组化法测定给药2、4、8周后的骨形态发生蛋白(BMP)-2和骨保护素(OPG)的表达;Westernblot法测定给药8周后的BMP-2和OPG蛋白的表达。结果:与DM骨折模型组比较,白藜芦醇组给药2、8周后的血糖含量显著降低,给药8周后血钙、血磷含量显著升高(P<0.01或P<0.05);给药2、4、8周后白藜芦醇组病理形态学显著改善;给药8周后,白藜芦醇组BMP-2表达显著增强,给药4、8周后OPG表达显著增强(P<0.01或P<0.05);给药8周后,白藜芦醇组BMP-2、OPG蛋白表达显著增强。结论:白藜芦醇可使DM骨折模型大鼠BMP-2、OPG的表达增强,这为白藜芦醇应用于DM骨折愈合的治疗提供了理论依据。

OBJECTIVE： To study the effects of resveratrol on the process of fracture healing in diabetic model rats. METH- ODS： Diabetic rat model was induced by streptozotocin via tail vein（60 mg/kg）. Left leg of rats was incised under sterilized condition to expose the upper part of left tibia; tibia was sawed off with wire saw （about 0.8 cm below tibial plateau）, reset, sutured and fixed with splint to induce DM cataclais model prats. Model rats were divided into 4 groups, i.e. control group （constant volume of normal saline）, DM cataclasis model group （constant volume of normal saline）, sodium fluoride group （20 mg/kg） and res- veratrol group （20 mg/kg）. They were given relevant medicine intragastrically once a day for 8 weeks. Blood glucose, calcium, phosphorus, alkaline phosphatase （ALP） after 2 and 8 weeks of treatment; pathomorphology was observed after 2, 4 and 8 weeks of treatment, and protein-2 （BMP-2） and osteoprotegerin （OPG） expression were detected by immunohistochemical method; BMP-2 and OPG expression were detected by Western blot after 8 weeks of treatment. RESULTS： Compared with DM cataclasis model group, blood glucose of resveratrol group decreased significantly after 2 and 8 weeks of treatment, blood calcium and phos- phate increased significantly after 8 weeks of treatment （P〈0.01 or P〈0.05） ; pathomorphology of resveratrol group improved significantly after 2, 4 and 8 weeks of treatment; BMP-2 expression of resveratrol group increased after 8 weeks of treatment,OPG expression of resveratrol group increased alier 2 and 8 weeks of treatment; protein of BMP-2 and OPG expression of resveratrol group increased after 8 weeks of treatment.CONCLUSION： Resveratrol can enhance the expression of BMP-2 and OPG in increase diabetes fracture rats, which larovide experimental basis for resveratrol applied in the treatment of diabetes fracture healing.