本文選題：二甲雙胍　切入點：絕經(jīng)后骨質(zhì)疏松癥　出處：《山西醫(yī)科大學》2017年碩士論文　論文類型：學位論文

【摘要】：目的:探討不同濃度二甲雙胍對去勢大鼠脛骨的骨密度(Bone mineral density,BMD)和骨生物力學的影響,探討通過應用二甲雙胍干預雙側(cè)卵巢摘除大鼠,檢測血清中晚期糖基化終產(chǎn)物變化從而確定其調(diào)控骨代謝的可行性,從而為骨質(zhì)疏松癥的臨床藥物防治提供依據(jù)。方法:使用SD雌鼠通過行假手術(shù)或雙側(cè)卵巢摘除術(shù)建立對照組模型(Sham組)及停經(jīng)后骨質(zhì)疏松癥模型(OVX組),分為4組,分別是Sham組,OVX組,OVX+50 mg/kg/day二甲雙胍組,OVX+100 mg/kg/day二甲雙胍組。3月后給予不同劑量二甲雙胍灌胃,Sham組、OVX組給予相應劑量0.9%生理鹽水,OVX+50mg/kg/day二甲雙胍組、OVX+100 mg/kg/day二甲雙胍組分別按50 mg/kg/day、100 mg/kg/day灌胃二甲雙胍。3月后處死大鼠,取血清、脛骨標本,應用雙能X線、生物力學、組織學方法檢測不同組別大鼠骨質(zhì)差異,應用酶聯(lián)免疫吸附試驗(ELISA)檢測并比較各組大鼠血清中晚期糖基化終產(chǎn)物(AGEs)表達水平及差異。結(jié)果:與Sham組相比,OVX組大鼠的脛骨骨質(zhì)呈現(xiàn)明顯的疏松多孔樣,骨密度明顯降低(P0.05),彈性模量和最大載荷也顯著下降(P0.05),血清中AGEs含量明顯升高(P0.05),灌胃二甲雙胍后,脛骨質(zhì)量有所改善,骨小梁分布較OVX組密集,骨密度升高(P0.05),彈性模量和最大載荷也增加(P0.05),同時血清中AGEs含量較OVX組顯著降低(P0.05),但均尚未達到Sham組水平(P0.05)。OVX+50 mg/kg/day二甲雙胍組與OVX+100 mg/kg/day二甲雙胍組實驗結(jié)果比較發(fā)現(xiàn):兩組大鼠血清中AGEs含量接近(P0.05),骨質(zhì)量、骨密度無明顯差異(P0.05),但彈性模量和最大載荷表現(xiàn)出劑量相關(guān)性(P0.05)。結(jié)論:1、二甲雙胍可提高去勢大鼠骨密度及骨生物力學參數(shù),具有改善停經(jīng)后骨質(zhì)疏松性骨折的作用。2、二甲雙胍可能通過降低絕經(jīng)后骨質(zhì)疏松大鼠血清中的AGEs含量進而改善骨代謝。
[Abstract]:Objective: to investigate the effects of metformin at different concentrations on bone mineral density (BMD) and bone biomechanics in ovariectomized rats, and to explore the effect of metformin on bilateral ovariectomized rats. To determine the feasibility of regulating bone metabolism by detecting the changes of advanced glycation end products in serum. Methods: SD female rats were used to establish control group by sham-operation or bilateral ovariectomies) and postmenopausal osteoporosis model OVX group were divided into 4 groups. OVX 50 mg / kg / kg / day metformin group OVX 100 mg/kg/day metformin group respectively. After March, different doses of metformin were given intragastrically to the 0.9% normal saline group with 50 mg / kg mg/kg/day / kg metformin group, and the OVX 100 mg/kg/day metformin group were given OVX 100 mg/kg/day metformin group respectively, after March, the OVX group received 50 mg / kg of normal saline and 50 mg / kg 路kg / day metformin group respectively, and the OVX 100 mg/kg/day metformin group was given OVX100 mg/kg/day metformin group respectively after March. The rats were given metformin at 50 mg / kg / kg / 100 mg/kg/day. After March, the rats were killed. Serum and tibia samples were collected and bone difference of different groups of rats was detected by dual-energy X-ray, biomechanics and histology. Enzyme linked immunosorbent assay (Elisa) was used to detect and compare the expression of advanced glycation end products (ages) in the serum of rats in each group. Results: compared with Sham group, the tibial bone of rats in OVX group was obviously porous and porous. The bone mineral density (BMD) decreased significantly (P 0.05), the modulus of elasticity and the maximum load also decreased significantly (P 0.05). The content of AGEs in serum increased significantly (P 0.05). After intragastric administration of metformin, the tibia quality was improved, and the distribution of bone trabeculae was denser than that in the OVX group. The content of AGEs in serum was significantly lower than that in OVX group, but it was still not up to the level of Sham group. OVX 50 mg/kg/day metformin group and OVX 100 mg/kg/day metformin group were compared with OVX 100 mg/kg/day metformin group. The content of AGEs in serum of the two groups was close to that of P0. 05, and the bone mass of the two groups was higher than that of the control group. There was no significant difference in bone mineral density (BMD), but there was a dose-dependent correlation between the modulus of elasticity and the maximum load. Conclusion the bone mineral density and bone biomechanical parameters of ovariectomized rats can be increased by 1: 1 and metformin. Metformin may improve bone metabolism by reducing serum AGEs content in postmenopausal osteoporosis rats.
【學位授予單位】：山西醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R580

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