舒洛地特对糖尿病大鼠骨质疏松症的影响

目的：评价低分子肝素类抗凝药物舒洛地特（Sulo-dexide）对糖尿病大鼠骨质疏松症的影响．方法：将SD大鼠随机分为3组：正常对照组（C组）、糖尿病模型组（D组）、舒洛地特治疗组（S组）．D组给予腹腔注射单剂量链脲佐菌素（STZ）诱导；S组每日给予舒洛地特10mg／（kg·d）灌胃；C，D组大鼠每日给予等量生理盐水灌胃，观察12wk后各组大鼠体质量及血糖变化．应用显微镜观察大鼠骨组织显微结构并进行骨组织形态密度计量学分析，用双能X线骨密度测量仪（DEXA）测定股骨骨密度（BMD）．采用逆转录-聚合酶链反应（RT-PCR）检测骨组织骨保护素（OPG）mRNA，核因子-KB受体活化因子配体（RANKL）mRNA的表达．结果：12wk末光镜下均可见D，S组骨组织骨质疏松表现，且2组骨质疏松程度相似．D，S组平均骨小梁厚度（MTPT）均显著低于C组（P〈0．01）；平均骨小梁间距或弥散度（MTPS）均显著高于C组（P〈0．01）；S组与D组骨组织相比较，MTPT及MTPS无显著性差异．与C组相比较，D，S组骨组织BMD值显著降低（P〈0．01）；S组骨组织BMD值与D组无显著性差异．D，S组骨组织OPGmRNA明显低于C组（P〈0．05），但RANKLmRNA表达均高于C组（P〈0．05）．D组与S组相比较，OPG mRNA及RANKL mRNA的表达无显著性差异．结论：糖尿病大鼠存在明显骨量减少和骨质疏松，舒洛地特对糖尿病大鼠骨质疏松症的骨质改变无明显影响．

Effects of sulodexide on osteoporosis in experimental diabetic rats

AIM： To study the effects of sulodexide on osteoporosis in experimental diabetic rats. METHODS： Sprague-Dawley （SD） rats were randomly divided into normal control group （ C）, diabetic group without treatment （D） and sulodexide treatment group（S）, and a single dose of streptozotocin was abdominally injected to establish the diabetic rat models. Each animal in sulodexide treated group was additionally fed daily with sulodexide of 10 mg/（ kg ·d） per day for 12 weeks, while the animals in the C and D groups were given only normal water during the same period. After 12 weeks of treatment, blood glucose and body weight were measured. Bone histomorphometry and bone mineral density were analyzed, and bone mineral density（BMD） of lumbar spines was determined by dual energy X-ray absorption （DEXA）. Reverse transeripfion-polymerase reaction （RT-PCR） was performed to detect the expression of OPG mRNA and RANKL mRNA in the sample bones. RESULTS： After 12 weeks, histomorphometry and the bone mineral density analysis showed that： osteoporosis was found in both D group and S group, and osteoporosis in S group was similar to that in D group. Compared with those in C group, mean trabecular plate thickness （MTPT） significantly decreased （P 〈 0. 01 ） and mean trabecular plate separation （MTPS） significantly elevated（ P 〈0.01 ） in both D group and S group. Compared with those in D group, MTT and MTPS had no obviously changes in S group. BDM results showed that： Compared with that in C group, BDM in D group and S group significantly decreased（P 〈0. 01）. BDM in S group had no significant changes compared with those in D group. RT-PCR showed that： OPG mRNA level deereased in D group and S group（P 〈0.05）. RANKL mRNA level increased in both D group and S group （ P 〈 0.05 ）. No significant difference was found in OPG mRNA and RANKL mRNA levels between D group and S group. CONCLUSION： Diabetic rats suffer from osteopnia and osteoporosis but sulodexide has