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高骨橋蛋白水平對(duì)雙足直立鼠脊柱側(cè)凸發(fā)生率和嚴(yán)重程度的影響及動(dòng)物模型建立相關(guān)研究

發(fā)布時(shí)間:2018-05-21 02:45

  本文選題:青少年特發(fā)性脊柱側(cè)凸 + 骨橋蛋白 ; 參考:《第二軍醫(yī)大學(xué)》2017年碩士論文


【摘要】:一、研究目的青少年特發(fā)性脊柱側(cè)凸(adolescent idiopathic scoliosis,AIS)是一種定義為十歲左右起病,并且沒(méi)有潛在的致病原因支持其發(fā)生及進(jìn)展的一類(lèi)脊柱三維畸形,女性較男性多發(fā)。目前AIS的病因和發(fā)病機(jī)制仍然缺乏足夠的認(rèn)識(shí),盡管提出大量的假設(shè),但尚未得到明確的論證。近年來(lái)相關(guān)研究揭示骨橋蛋白(osteopontin,OPN)可能導(dǎo)致特發(fā)性脊柱側(cè)凸發(fā)生發(fā)展。因此,本課題擬建立高OPN水平雙足直立小鼠,觀察評(píng)估高濃度OPN小鼠和對(duì)照組之間脊柱側(cè)凸發(fā)生率及嚴(yán)重程度的差異,并收集小鼠血清測(cè)量OPN濃度,驗(yàn)證單純高OPN濃度是否能夠直接誘發(fā)脊柱側(cè)凸發(fā)生。此外,我們還建立了高濃度骨橋蛋白水平誘導(dǎo)的雌性雙足直立小鼠,并評(píng)估其側(cè)凸發(fā)生率及嚴(yán)重程度,論證其是否能作為新型藥物干預(yù)類(lèi)AIS動(dòng)物模型平臺(tái)。二、研究方法(一)選取體重相近的同周齡C3Heej雄性小鼠120只,隨機(jī)均分為3個(gè)組,其中2組于3周齡時(shí)行上肢及鼠尾切除術(shù),并分別腹腔注射高濃度OPN及生理鹽水,3組均通過(guò)特殊鼠籠誘導(dǎo)小鼠直立體態(tài)形成3個(gè)月,拍攝X線觀察比較各組小鼠脊柱側(cè)凸發(fā)生率及嚴(yán)重程度,同時(shí)收集小鼠血清,使用ELISA方法測(cè)定各組小鼠血清OPN濃度差異。(二)選取體重相近的同周齡C3Heej雄性及雌性小鼠共80只,分為高OPN雌性組、高OPN雄性組、對(duì)照組雄性組及對(duì)照組雌性組4個(gè)組,每組各20只,同法誘導(dǎo)小鼠脊柱直立體態(tài)3個(gè)月,拍攝X線觀察比較各組小鼠脊柱側(cè)凸發(fā)生率及嚴(yán)重程度。三、研究結(jié)果(一)3個(gè)月后高OPN雙足鼠組、對(duì)照雙足鼠組、對(duì)照四足鼠組血清OPN濃度分別為207.3±85.1 ng/ml、74.6±20.1 ng/ml、83.7±32.2 ng/ml,高濃度OPN組外周血內(nèi)OPN含量明顯升高。小鼠體長(zhǎng)分別為(13.6±1.0)cm、(13.9±0.9)cm、(13.6±0.9)cm。平均Cobb角角度分別為(29.8±6.1)°、(20.1±4.4)°、(16.6±2.9)°,側(cè)凸發(fā)生率分別為92.5%、52.1%、12.5%。各組小鼠體長(zhǎng)未見(jiàn)明顯差異,高OPN雙足鼠組側(cè)凸發(fā)生率及嚴(yán)重程度較對(duì)照組明顯加重,差異有統(tǒng)計(jì)學(xué)意義。(二)高OPN雌性雙足鼠組、高OPN雄性雙足鼠組、對(duì)照組雌性組、對(duì)照組雄性組Cobb角分別為(25.8±6.7)°、(20.9±6.8)°、(15.6±3.1)°、(17.1±4.5)°,側(cè)凸發(fā)生率分別為90%、80%、40%、45%。高OPN雌性組、高OPN雄性組相比對(duì)照組之間,側(cè)凸發(fā)生率及嚴(yán)重程度差異有顯著性,高OPN雌性組較OPN雄性組脊柱側(cè)凸嚴(yán)重程度更重,差異有統(tǒng)計(jì)學(xué)意義。四、結(jié)論本研究結(jié)果在動(dòng)物模型上證實(shí)了高OPN水平可能在青少年特發(fā)性脊柱側(cè)凸的發(fā)病機(jī)制中發(fā)揮重要作用:其不僅提高了在雙足直立小鼠發(fā)生脊柱側(cè)凸的風(fēng)險(xiǎn),而且也與側(cè)凸曲度的進(jìn)展密切相關(guān),實(shí)驗(yàn)結(jié)果證實(shí)高OPN是導(dǎo)致AIS發(fā)病及進(jìn)展的重要因素;高濃度OPN水平誘導(dǎo)的雌性雙足直立小鼠其側(cè)凸發(fā)生率更高,側(cè)凸嚴(yán)重程度較重,其更貼近于人類(lèi)特發(fā)性脊柱側(cè)凸女性高發(fā)的實(shí)際情況,可作為新型藥物干預(yù)類(lèi)特發(fā)性脊柱側(cè)凸良好的動(dòng)物模型平臺(tái)。
[Abstract]:First, adolescent idiopathic scoliosis (AIS) is a class of spinal three-dimensional deformities defined as the onset of the onset of ten years old and without potential cause for disease. Women are more likely than men. At present, the cause and pathogenesis of AIS are still lacking enough understanding, though A large number of hypotheses have not yet been demonstrated. In recent years, relevant studies have revealed that osteopontin (OPN) may lead to the development of idiopathic scoliosis. Therefore, a high OPN level bipedal erect mouse is proposed to assess the incidence of scoliosis and the severity of scoliosis between high concentration OPN mice and control groups. In addition, the concentration of OPN in the serum of mice was collected to verify whether the pure high OPN concentration could induce scoliosis directly. In addition, we also established a high concentration osteopontin level induced female bipedal erect mouse, and evaluated the incidence and severity of scoliosis, and demonstrated whether it could be used as a new drug intervention AIS animal model. Platform. Two. Study method (1) 120 C3Heej male mice with similar weight of the same week age were selected and divided into 3 groups randomly, of which 2 groups were treated with upper limb and tail excision at 3 weeks of age, and high concentration of OPN and saline were injected into the abdominal cavity respectively. The 3 groups were induced by special squirrel cage to form the erect state for 3 months. The incidence of scoliosis and the severity of scoliosis in mice were collected and the serum levels of OPN were collected by ELISA method. (two) a total of 80 C3Heej male and female mice of the same body weight were selected to be divided into high OPN female group, high OPN male group, the control group male group and the control group of 4 groups, with 20 rats in each group. The incidence of scoliosis and severity of scoliosis in mice were compared for 3 months. Three, the results of the study were (1) high OPN bipedal rats after 3 months. The serum OPN concentration of the control quadruped rat group was 207.3 + 85.1 ng/ml, 74.6 + 20.1 ng/ml, 83.7 + 32.2 ng/ml, and high concentration OPN group peripheral blood. The content of internal OPN increased significantly. The body length of the mice was (13.6 + 1) cm, (13.9 + 0.9) cm and (13.6 + 0.9) cm., respectively (29.8 + 6.1), (20.1 + 4.4) degrees, (16.6 + 2.9) degrees, and the incidence of scoliosis was 92.5%, 52.1%, and 12.5%., respectively. The incidence and severity of scoliosis in the high OPN bipedal rats were more than that of the control group. The difference was statistically significant. (two) high OPN female bipedal rats, high OPN male bipedal rats, control group female group, and control group male group Cobb angle respectively (25.8 + 6.7) degrees, (20.9 + 6.8) degrees, (15.6 + 3.1) degrees, (17.1 + 4.5) degrees, the incidence of scoliosis was 90%, 80%, 40%, high OPN female group, high OPN male group compared to the control group, to the side of the control group, to the side of the control group, to the side, to the side, to the side, to the side, to the side, to the side, to the side, to the side, to the side, to the side, to the side, to the side, to the side, to the side, to the side, to the side, to the side, to the side, to the side, to the side, to the side, to the side, to the side, to the side, to the side, to the side, to the side, to the side, to the side, to the side, to the side, to the side, to the side, to the side, to the side, to the side, to the side, to the side, to the side, to the side, to the side, to the side, to the side, to the side, to the side, to the side of the control group. There is a significant difference in the incidence and severity of convexity. The high OPN female group is more serious than the OPN male scoliosis, and the difference is statistically significant. Four. Conclusion the results of this study suggest that high OPN level in the animal model may play an important role in the pathogenesis of adolescent idiopathic scoliosis: it not only improves the double foot in the bipedal system. The risk of scoliosis in erect mice is related to the risk of scoliosis and is closely related to the progression of scoliosis. Experimental results confirm that high OPN is an important factor leading to the onset and progression of AIS. High concentration of OPN level induced female double foot erect mice have higher incidence of scoliosis and severe scoliosis, which is more close to human idiopathic scoliosis. The practical situation of high incidence can be used as a good animal model platform for new drugs to intervene in idiopathic scoliosis.
【學(xué)位授予單位】:第二軍醫(yī)大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2017
【分類(lèi)號(hào)】:R726.8

【參考文獻(xiàn)】

相關(guān)期刊論文 前7條

1 李倫超;劉湘;朱青安;黃志平;任海龍;鄭帥;李廣軍;楊德鴻;王吉興;;單側(cè)橫突拉簧加壓建立兔脊柱側(cè)凸模型[J];南方醫(yī)科大學(xué)學(xué)報(bào);2015年04期

2 張漢慶;戴q,

本文編號(hào):1917411


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