伊贝沙坦对糖尿病大鼠骨质疏松影响的实验研究

Experiment study on the effect of Irbesartan on the diabetic osteoporosis rats

目的探讨伊贝沙坦对糖尿病大鼠骨质疏松的干预作用及其机制。方法雄性SD大鼠按体重随机分为正常对照组(C组)、糖尿病组(D组)、伊贝沙坦治疗组(I组)。糖尿病大鼠模型经单剂量腹腔注射链脲佐菌素(STZ)制成。所有大鼠均给以普通饲料喂养,I组大鼠每天以伊贝沙坦15mg·kg-1·d-1灌胃,C组和D组大鼠每天予等量生理盐水灌胃,第12周末,测体重及血糖,处死大鼠后取骨,应用显微镜观察骨组织显微结构和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)测定大鼠股骨骨密度(BMD),采用逆转录-聚合酶链反应(RT-PCR)检测各组骨组织OPG mRNA及RANKL mRNA的表达。结果12周末,D组和I组大鼠骨组织光镜下均出现骨质疏松表现,I组骨质疏松程度比D组轻。骨组织定量分析显示,MTPT在D组及I组均显著低于C组(P<0.01),MTPS在D组及I组均显著高于C组(P<0.01)。I组与D组大鼠骨组织相比,MTPT显著增加及MTPS显著降低(P<0.01)。骨密度的测定结果发现,与C组大鼠比较,D组和I组大鼠骨组织BMD值显著降低(P<0.01);而I组大鼠骨组织BMD值又较D组显著增加(P<0.01)。骨组织RT-PCR结果显示,与C组相比,D组和I组大鼠骨组织中OPG mRNA表达水平明显降低(P<0.01),RANKL mRNA表达水平明显升高(P<0.01);I组大鼠骨组织中OPG mRNA的表达则明显高于D组(P<0.01),而RANKL mRNA在I组和D组间差异不显著。结论伊贝沙坦可使糖尿病大鼠骨组织降低的OPG mRNA表达水平得以部分恢复,上调OPG/RANKL比值,这可能与伊贝沙坦的改善糖尿病大鼠骨质疏松的效应有关。

Objective To study the effect of Irbesartan on preventing the osteoporosis in the diabetic rats. Methods 36 male Sprague-Dawley（SD） rats were randomly divided into normal control group （C） ,diabetic group without treatment（ D）, and Irbesartan treatment group（ I）, a single dose of streptozotocin were abdominally injected to establish the diabetic rat models. All the rats were fed daily with ordinary food. Each animal in Irbesartan treated group was additionally fed daily with Irbesartan of 15 mg·kg^-1· d^-1 per day for 12 weeks, while the remaining group （C and D）were given normal water only for equal time. After 12 weeks of treatment, Blood glucose and Body weight were measured. The bone histomorphometry and the bone mineral density were analyzed, Dual energy X-ray absorption（ DEXA）was used to determine the bone mineral density（BMD） of lumbar spines. Reverse transcription-pelymerase reaction （RT-PCR） was performed to detect the expression of OPG mRNA and RANKL mRNA in the tissue samples bone. Results After 12 weeks, histomorphometry and the bone mineral density analysis showed that：osteoperosis was found both in D group and I group, but I group was lighter than D group： Compared with the C group, MTPT significantly decreased（ P 〈 0.01 ） and MTPS was significantly elevated（ P 〈 0.01 ） both in D group and I group; While compared with the D group, MTPF obviously increased（ P 〈 0.01 ）and MTPS obviously decreased （P 〈 0.01 ）in I group. BDM result showed that： Compared with the C group, BDM in D group and I group significantly decreased（ P 〈 0.01 ）; While compared with the D group, BDM in I group significantly increased （ P 〈 0.01 ）. RT-PCR result： compared with the C group, the OPG mRNA expression significantly decreased（ P 〈 0.01 ）and the RANKL mRNA expression obviously elevated（ P 〈 0.01 ）both in D group and I group; the expressions of OPG mRNA in I group tended to be stronger than that in D group（ P 〈 0.01 ） ,but the expression of RANKL mRNA in I group had no significant change compared with that of in D group （ P 〈 0.01 ）. Conclusions Irbesartan may improve diabetic osteoporosis by upregulating the OPG mRNA expression and OPG/RANKL ratio.