【摘要】：目的:β-arrestin2是一種轉(zhuǎn)接器蛋白,與G蛋白偶聯(lián)受體結(jié)合,參與發(fā)揮多種生物學(xué)效應(yīng)。本研究的目的是探討β-arrestin2缺失對(duì)小鼠骨量的影響及其可能發(fā)生機(jī)理。方法:采用16,26,30周齡β-arrestin2敲除雌鼠和野生型雌鼠。小鼠通過腹腔注射1%戊巴比妥進(jìn)行麻醉,利用雙能X線吸收儀(Dual-energy-X-ray-absorptiometry,DXA)檢測(cè)敲除和野生型鼠全身骨密度,微型計(jì)算機(jī)斷層掃描技術(shù)(Micro-computed tomography,u CT)檢測(cè)股骨微結(jié)構(gòu),RT-PCR檢測(cè)脛骨骨形成、骨吸收相關(guān)因子和G蛋白偶聯(lián)雌激素受體1(GPER1)的m RNA表達(dá)。結(jié)果:β-Arrestin2敲除雌鼠在16周齡開始出現(xiàn)全身骨密度降低,分別于16、26、30周降低了8.10%、7.53%、8.56%。u CT骨微結(jié)構(gòu)檢測(cè)顯示上述三個(gè)周齡鼠骨體積分?jǐn)?shù),和骨小梁數(shù)量均較野生型鼠減少(骨體積分?jǐn)?shù):分別下降53.3%、49.4%和55.7%;骨小梁數(shù)量:分別下降53.2%、52.1%和49.3%),與各自的對(duì)照組野生型小鼠相比,差異均具有統(tǒng)計(jì)學(xué)顯著性(all P0.05)。同時(shí),隨著周齡的增長(zhǎng),敲除雌鼠骨小梁模式因子、間距、結(jié)構(gòu)模型指數(shù)差異逐漸增大,至30周時(shí)與對(duì)照野生小鼠相比達(dá)到統(tǒng)計(jì)學(xué)顯著差異(分別增加了32.0%、54.3%、23.7%)(all P0.05)。脛骨組織RT-PCR檢測(cè)顯示護(hù)骨素(OPG),破骨細(xì)胞分化因子(RANKL)和GPER1m RNA表達(dá)均降低,與對(duì)照組有明顯差異(P0.05)。結(jié)論:β-Arrestin2缺失導(dǎo)致小鼠骨重塑、骨量下降,該改變與GPER1表達(dá)下降相關(guān),提示β-arrestin2缺失對(duì)小鼠骨代謝的影響可能通過G蛋白偶聯(lián)雌激素受體信號(hào)通路。
[Abstract]:Aim: 尾-arrestin2 is a type of protein that binds to G protein and plays a variety of biological effects. The aim of this study was to investigate the effect of 尾-arrestin2 deletion on bone mass in mice and its possible mechanism. Methods: 尾-arrestin2 knockout female and wild type female were used. Mice were anesthetized by intraperitoneal injection of 1% pentobarbital. Bone mineral density (BMD) of knockout and wild-type mice was measured by dual energy X-ray absorptiometry (Dual-energy-X-ray-absorptiometry,DXA) and Micro-computed tomography,. Microstructures of femur were detected by u CT), bone formation of tibia, bone resorption related factor and m RNA expression of G protein-coupled estrogen receptor 1 (GPER1) were detected by RT-PCR. Results: the bone mineral density of 尾-Arrestin2 knockout female rats began to decrease at the age of 16 weeks, and the bone mass fraction of the three week old rats was decreased by 8.10% 7.53 and 8.56% at 162630 weeks, respectively. The results showed that the bone volume fraction of the three weeks old rats mentioned above was lower than that of the control group. The number of trabeculae and bone trabeculae were decreased (bone volume fraction: 53.3%, 49.4% and 55.7%, respectively); The number of trabeculae decreased by 53.1% and 49.3%, respectively, compared with the control group, the difference was statistically significant (all P0.05). At the same time, with the increase of age, the differences of trabecular model factors, spacing and structural model index increased gradually, and at 30 weeks the difference was statistically significant compared with the control wild mice (increased 32.0% and 54.3%, respectively). 23.7%) (all (P0.05). The expression of osteoclast differentiation factor (RANKL) and osteoclast differentiation factor (GPER1m RNA) in osteoclast of osteoprotegerin (OPG),) was significantly lower than that in the control group (P0.05). Conclusion: 尾-Arrestin2 deficiency can induce bone remodeling and decrease of bone mass in mice. This change is related to the decrease of GPER1 expression, suggesting that the effect of 尾-arrestin2 deletion on bone metabolism may be mediated by G protein-coupled estrogen receptor signaling pathway.
【學(xué)位授予單位】：上海交通大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：R580

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本文編號(hào)：2387683