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脂肪因子Chemerin與骨質(zhì)疏松、骨折相關(guān)性

發(fā)布時(shí)間:2018-06-04 11:26

  本文選題:Chemerin + 骨質(zhì)疏松。 參考:《長江大學(xué)》2016年碩士論文


【摘要】:背景:隨著國內(nèi)經(jīng)濟(jì)建設(shè)的快速發(fā)展,物質(zhì)生活水平的快速提高和交通運(yùn)輸?shù)陌l(fā)達(dá),人口老齡化問題越來越嚴(yán)重,相應(yīng)的骨質(zhì)疏松和骨折以及由骨質(zhì)疏松引起的骨折越來越多,在骨科臨床上成為常見病和多發(fā)病;颊叱霈F(xiàn)骨質(zhì)疏松,以及由于骨質(zhì)疏松引起的骨折等,病程時(shí)間長,臨床癥狀明顯,給患者及其家庭帶來沉重的經(jīng)濟(jì)負(fù)擔(dān),給社會帶來嚴(yán)重的壓力。骨質(zhì)疏松是一種代謝性骨病,發(fā)生骨質(zhì)疏松的病因比較復(fù)雜,目前并沒有確定其明確的病因?qū)W發(fā)病機(jī)制。目前主要有以下幾個(gè)方面的研究:一是遺傳的因素。VDR(Vitamin D receptor)基因與骨密度相關(guān),維生素D對骨代謝具有重要的調(diào)節(jié)作用。生長因子β(TGF-β)基因,有研究證明,TGF-β基因變異者,骨密度顯著降低。二是營養(yǎng)及運(yùn)動因素。老年人消化功能減弱,多有蛋白質(zhì)、鈣、微量元素等攝入不足。此外,老年人運(yùn)動減少也是發(fā)生骨質(zhì)疏松的重要因素。三是內(nèi)分泌因素。包括性激素,降鈣素以及脂肪因子等。雌激素受體(estrogen receptor, ER)在人成骨細(xì)胞和破骨細(xì)胞的存在已被證實(shí),其基因與骨密度有一定關(guān)系。雌激素和成骨細(xì)胞和破骨細(xì)胞上的受體結(jié)合,阻止骨的再吸收。破骨細(xì)胞上有降鈣素的受體,降鈣素與其結(jié)合后能夠抑制其細(xì)胞活性。近年研究表明,脂肪組織具有內(nèi)分泌調(diào)節(jié)功能,可分泌多種細(xì)胞因子,稱為脂肪因子,包括趨化素(chemerin)、瘦素(leptin)、脂聯(lián)素(adiponectin)、抵抗素(resistin)等。脂肪因子不僅參與體內(nèi)能量代謝、糖脂代謝,還參與炎癥和免疫反應(yīng),對維持骨代謝的平衡起著重要的作用。各種原因?qū)е碌墓橇繙p少常伴有骨髓中脂肪組織含量的增加。骨髓中脂肪組織在骨的形成和造血中發(fā)揮重要作用。從脂肪因子chemerin受體及chemerin的先后被發(fā)現(xiàn),其在骨代謝中的作用,及在骨質(zhì)疏松中的作用逐漸被受到重視。本實(shí)驗(yàn)?zāi)康氖墙⒋笫蠊琴|(zhì)疏松模型和股骨骨折模型,初步分析血清中脂肪因子Chemerin與骨質(zhì)疏松、骨折的相關(guān)性,以期為進(jìn)一步的動物實(shí)驗(yàn)及臨床研究提供實(shí)驗(yàn)基礎(chǔ)。目的:本實(shí)驗(yàn)通過建立大鼠骨質(zhì)疏松模型及股骨骨折模型,為進(jìn)一步研究脂肪因子Chemerin與骨質(zhì)疏松、骨折的提供實(shí)驗(yàn)基礎(chǔ)。通過分組對照,在不同時(shí)間段測定大鼠血清中Chemerin的濃度,來了解Chemerin與骨質(zhì)疏松、骨折的相關(guān)性。如果證明Chemerin對骨質(zhì)疏松的發(fā)病機(jī)制及骨折的恢復(fù)有調(diào)控作用,可為進(jìn)一步研究其具體調(diào)控機(jī)制和治療骨質(zhì)疏松及促進(jìn)骨折愈合方面開辟新的途徑和治療方法。方法:選用30只雌性Wistar大鼠,體重120-170g。大鼠按照完全隨機(jī)原則分為五組,每組6只。A組為假手術(shù)(SHAM)組,B組為單純?nèi)ヂ殉步M(Ovariectomy, OVX), C組為單純?nèi)ヂ殉泊萍に刂委熃M(OVX+E2), D組為單純?nèi)ヂ殉膊⒐晒枪钦劢M(OVX+FF), E組為單純股骨骨折組(Femoral fractures, FF)。骨質(zhì)疏松模型的建立采用切除卵巢方法。3月后確定骨質(zhì)疏松模型建立成功后,測A組和B組血清中Chemmerin的濃度,D組和E組行股骨骨折模型的建立。股骨骨折模型的建立采用閉合骨折模型方法。建立股骨骨折模型后,分別在以后的1周、2周、4周對A、B、D、E四組大鼠血清中Chemmerin的濃度進(jìn)行檢測比較。確定C組骨質(zhì)疏松模型建立后,給予雌激素每天5ug,連續(xù)6周,測骨密度和血清Chemerin濃度,并與B組比較。血清Chemerin濃度檢測方法為酶聯(lián)免疫吸附法(ELISA)。結(jié)果:卵巢切除致骨質(zhì)疏松雌激素治療組(C組)經(jīng)雌激素治療6周后與單純?nèi)ヂ殉矊?dǎo)致骨質(zhì)疏松組(B組)血Chemerin濃度比較,血Chemerin濃度在兩組之間無顯著意義(P0.05);卵巢切除致骨質(zhì)疏松雌激素治療組(C組)經(jīng)雌激素治療6周后,與單純?nèi)ヂ殉矊?dǎo)致骨質(zhì)疏松組(B組)腰椎BMD比較,C組較B組腰椎骨密度增加,差異具有顯著性(P0.05);術(shù)后12周確定骨質(zhì)疏松模型建立后,單純?nèi)ヂ殉步M(B組)與假手術(shù)(SHAM)組(A組)血Chemerin濃度比較,B組較A組血清Chemerin濃度增高,差異具有顯著性(P0.05);單純股骨骨折組(E組)與假手術(shù)(SHAM)組(A組)血Chemerin濃度比較,E組較A組血清Chemerin濃度增高,差異具有顯著性(P0.05),單純?nèi)ヂ殉膊⒐晒枪钦劢M(D組)與單純?nèi)ヂ殉步M(B組)血Chemerin比較,D組較B組血清Chemerin濃度增高,差異具有顯著性(P0.05)。結(jié)論:雌激素對血清Chemerin濃度水平無顯著性影響;雌激參與了骨質(zhì)疏松的病理生理過程;Chemerin參與了骨質(zhì)疏松的病理生理過程;Chemerin參與了骨折的修復(fù)過程。
[Abstract]:Background: with the rapid development of domestic economic construction, the rapid improvement of the material living standard and the developed transportation, the problem of population aging is becoming more and more serious. The corresponding osteoporosis and fracture, as well as more and more fractures caused by osteoporosis, are common diseases and frequently occurring diseases in the Department of orthopedics. And the fracture caused by osteoporosis, which has a long course and obvious clinical symptoms, brings heavy economic burden to the patients and their families and brings serious pressure to the society. Osteoporosis is a metabolic bone disease, and the cause of osteoporosis is complicated. At present, the pathogenesis of the etiology is not definite. There are several studies in the following aspects: one is that the genetic factor.VDR (Vitamin D receptor) is associated with bone mineral density, and vitamin D has an important regulatory effect on bone metabolism. The gene of growth factor beta (TGF- beta) has proved that the bone density of the TGF- beta gene mutation is significantly lower. Two is the nutritional and sports factors. The digestive function of the elderly is weakened, More protein, calcium, and trace elements are insufficient. In addition, the decrease of exercise in the elderly is also an important factor in osteoporosis. Three is endocrine factors, including sex hormones, calcitonin, and adipose factors. The presence of estrogen receptor (ER) in human osteoblasts and osteoclasts has been confirmed, and its gene and bone mineral density There is certain relationship. Estrogen is combined with osteoblasts and osteoclasts to prevent the reabsorption of bone. There are calcitonin receptors on osteoclasts. Calcitonin and its binding can inhibit cell activity. In recent years, studies have shown that adipose tissue has endocrine regulatory functions, which can secrete a variety of cytokines, called adipose factors, including fat factors. Chemokine (Chemerin), leptin (leptin), adiponectin (adiponectin), resistin (resistin) and so on. Adipose factors not only participate in energy metabolism, glycolipid metabolism, but also participate in inflammation and immune response, which play an important role in maintaining the balance of bone metabolism. Intramedullary adipose tissue plays an important role in bone formation and hematopoiesis. The role of the fat factor Chemerin receptor and Chemerin has been found, and its role in bone metabolism and its role in osteoporosis is gradually paid attention. The aim of this experiment was to establish a rat model of osteoporosis and fracture of the femur, and to preliminarily analyze the serum lipids. In order to provide experimental basis for further animal experiment and clinical research, the correlation of fat factor Chemerin with osteoporosis and fracture is expected to provide experimental basis for further animal experiment and clinical study. Determine the concentration of Chemerin in rat serum at different time to understand the correlation between Chemerin and osteoporosis and fracture. If it is proved that Chemerin has a regulatory effect on the pathogenesis of osteoporosis and the recovery of fracture, it can open up a new way to further study its specific regulation mechanism and the treatment of osteoporosis and promote fracture healing. Methods and methods. Methods: 30 female Wistar rats were selected and the body weight 120-170g. rats were divided into five groups according to the complete random principle, 6.A groups in each group were sham operation (SHAM) group, B group was pure ovariectomized group (Ovariectomy, OVX), C group was simple ovariectomized estrogen treatment group (OVX+E2), D group was simple ovariectomized and femur fracture group (OVX+FF), E group, E group For the simple femoral fracture group (Femoral fractures, FF). The establishment of the osteoporosis model was established by the method of ovariectomy and the establishment of the osteoporosis model after.3 months. The concentration of Chemmerin in the serum of A and B groups was measured. The model of femur fracture was established in group D and E. The model of femur fracture was established by closed fracture model method. After the bone fracture model, the concentrations of Chemmerin in the serum of A, B, D, E four rats were compared at the next 1 weeks, 2 weeks and 4 weeks. After the establishment of the osteoporosis model in group C, estrogen was given 5ug every day for 6 weeks, bone density and serum Chemerin concentration were measured and compared with the B group. The serum Chemerin concentration detection method was enzyme linked immunosorbent assay. Method (ELISA). Results: after 6 weeks of estrogen therapy, ovariectomized osteoporosis estrogen therapy group (group C) was compared with the blood Chemerin concentration in the group of osteoporosis group (group B) with simple ovariectomy. The concentration of Chemerin in the blood was not significant between the two groups (P0.05); the ovariectomized osteoporosis estrogen therapy group (group C) was treated with estrogen for 6 weeks after estrogen treatment, Compared with BMD in the osteoporotic group (group B), the BMD of the lumbar spine in the group C was higher than that in the B group, and the difference was significant (P0.05). After the establishment of the osteoporosis model at 12 weeks after the operation, the serum Chemerin concentration of the simple ovariectomized group (B group) and the sham operation group (A group) was compared, and the B group was higher than the A group, and the difference was significant. Compared with the blood Chemerin concentration in group E and group SHAM (group A), the concentration of serum Chemerin in group E was higher than that in group A (group SHAM), and the difference was significant (P0.05). Compared with the simple ovariectomized group (D group) and the simple ovariectomized group (B group), the concentration of serum Chemerin was higher than that in the group of A. P0.05. Conclusion: estrogen has no significant effect on the level of serum Chemerin concentration; estrogen is involved in the pathophysiological process of osteoporosis; Chemerin is involved in the pathophysiological process of osteoporosis, and Chemerin is involved in the process of fracture repair.
【學(xué)位授予單位】:長江大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2016
【分類號】:R580;R683

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10 吳穹;DKK1合成多肽對治療骨質(zhì)疏松癥和成骨作用的研究[D];南京大學(xué);2011年

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10 王姍姍;磷酸化南極磷蝦肽增加骨質(zhì)疏松癥大鼠的骨密度及其作用機(jī)制研究[D];中國海洋大學(xué);2015年

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