摘要
目的研究吡格列酮对去卵巢大鼠骨质疏松症的影响及机制。方法将SD大鼠随机分为假手术组、模型组、实验组和阳性对照组,每组15只。通过完整摘除两侧卵巢构建绝经后骨质疏松(PMOP)大鼠模型,假手术组仅摘除卵巢周围脂肪组织。实验组大鼠灌服10 mg·kg^-1吡格列酮,阳性对照组皮下注射苯甲酸雌二醇200μg·kg^-1,模型组、假手术组均灌胃等量0. 9%Na Cl,各组均连续灌服8周。用酶联免疫吸附实验(ELISA)测定大鼠血清骨保护素(OPG)、碱性磷酸酶(ALP)、Ⅰ型原胶原分子N端前肽(PINP)、抗酒石酸酸性磷酸酶(TRAP)指标水平;用Micro-CT及双能X线骨密度仪检测大鼠骨密度(BMD)。以实时荧光定量-聚合酶链式反应(q PCR)检测成骨分化相关基因表达水平。结果假手术组、模型组、实验组和阳性对照组大鼠血清OPG分别为(1. 52±0. 26),(1. 19±0. 21),(1. 06±0. 22),(1. 45±0. 33)μg·L^-1,ALP分别为(39. 24±3. 22),(22. 51±2. 24),(20. 43±1. 35),(35. 25±2. 32) U·L^-1,PINP分别为(12. 54±3. 06),(17. 58±2. 69),(19. 62±1. 52),(14. 22±3. 06)μg·L^-1,TRAP分别为(12. 42±2. 38),(16. 54±1. 54),(18. 33±2. 04),(14. 35±2. 15) U·L^-1;大鼠总BMD分别为(0. 19±0. 01),(0. 16±0. 01),(0. 15±0. 01),(0. 17±0. 01) g·cm^-1,椎骨BMD分别为(0. 17±0. 01),(0. 14±0. 01),(0. 13±0. 01),(0. 15±0. 01) g·cm^-1,股骨BMD分别为(0. 15±0. 01),(0. 13±0. 01),(0. 12±0. 01),(0. 14±0. 01) g·cm^-1,RUNX2mRNA相关表达量分别为1. 00±0. 10,1. 36±0. 10,1. 03±0. 26,1. 24±0. 03,CTSK mRNA相关表达量分别为1. 00±0. 06,1. 52±0. 14,1. 68±0. 14,0. 54±0. 12,差异均有统计学意义(均P <0. 05)。结论吡格列酮能降低PMOP大鼠骨密度,提高骨质疏松骨折发生的风险,与抑制成骨形成相关基因表达,促进破骨形成相关基因表达有关。
Objective To investigate the effect and mechanism of pioglitazone on osteoporosis in ovariectomized rats. Methods SD rats were randomly divided into sham operation group,model group,test group and positive control group with 15 rats in each group,postmenopausal osteoporosis ( PMOP) rat model was established by complete removal of bilateral ovaries. In the sham operation group,only adipose tissue around ovaries was removed. Rats in the test group were given orally pioglitazone for 10 mg·kg - 1 . which in the positive control group was subcutaneous injection of estradiol benzoate 200 μg·kg^-1,which in the model group and sham operation group were given orally the same amount of 0. 9% NaCl for 8 weeks. The serum levels of osteoprotegerin ( OPG),alkaline phosphatase ( ALP),procollagen type Ⅰ N - terminal propeptide ( PINP),tartrate - resistant acid phosphatase ( TRAP) were measured by enzyme - linked immunosorbent assay ( ELISA),and bone mineral density ( BMD) was measured by micro - CT and dual - energy X - ray absorptiometry. The expression of osteoblast differentiation related genes mRNA were detected by real - time fluorescence quantification - polymerase chain reaction ( qPCR). Results The serum OPG of sham operation group,model group,test group and positive control group were ( 1. 52 ± 0. 26),( 1. 19 ± 0. 21),( 1. 06 ± 0. 22),( 1. 45 ± 0. 33)μg·L^-1 respectively,the ALP were ( 39. 24 ± 3. 22),( 22. 51 ± 2. 24),( 20. 43 ± 1. 35),( 35. 25 ± 2. 32) U·L^-1, the PINP were ( 12. 54 ± 3. 06),( 17. 58 ± 2. 69),( 19. 62 ± 1. 52),( 14. 22 ± 3. 06)μg·L^-1,the TRAP were ( 12. 42 ± 2. 38),( 16. 54 ± 1. 54),( 18. 33 ± 2. 04),( 14. 35 ± 2. 15) U·L^-1;the total BMD were ( 0. 19 ± 0. 01),( 0. 16 ± 0. 01),( 0. 15 ± 0. 01),( 0. 17 ± 0. 01) g·cm - 1,vertebra BMD were ( 0. 17 ± 0. 01),( 0. 14 ± 0. 01),( 0. 13 ± 0. 01),( 0. 15 ± 0. 01) g·cm^-1,femoral BMD were ( 0. 15 ± 0. 01),( 0. 13 ± 0. 01),( 0. 12 ± 0. 01),( 0. 14 ± 0. 01) g·cm^-1,the relative expression of RUNX2 mRNA were 1. 00 ± 0. 10,1. 36 ± 0. 10,1. 03 ± 0. 26, 1. 24 ± 0. 03,the relative expression of CTSK mRNA were 1. 00 ± 0. 06,1. 52 ± 0. 14,1. 68 ± 0. 14,0. 54 ± 0. 12,the difference was statistically significant( P < 0. 05). Conclusion Pioglitazone can reduce bone mineral density and increase the risk of osteoporosis fracture in PMOP rats,which is related to inhibiting gene expression related to osteogenesis and promoting gene expression related to osteoclast formation.
作者
沈健
陈秋晴
曹兰兰
胡颖
熊国平
SHEN Jian;CHEN Qiu-qing;CAO Lan-lan;HU Ying;XIONG Guo-ping(Department of Obstetrics and Gynecology, Wuhan Central Hospital, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province,China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2019年第13期1359-1362,共4页
The Chinese Journal of Clinical Pharmacology
关键词
绝经后骨质疏松
吡格列酮
骨密度
骨代谢
postmenopausal osteoporosis
pioglitazone
bone mineral density
bone metabolism
