脂肪因子Chemerin与骨质疏松、骨折相关性

发布时间：2018-06-04 11:26

本文选题：Chemerin + 骨质疏松　；参考：《长江大学》2016年硕士论文

【摘要】：背景：随着国内经济建设的快速发展,物质生活水平的快速提高和交通运输的发达,人口老龄化问题越来越严重,相应的骨质疏松和骨折以及由骨质疏松引起的骨折越来越多,在骨科临床上成为常见病和多发病。患者出现骨质疏松,以及由于骨质疏松引起的骨折等,病程时间长,临床症状明显,给患者及其家庭带来沉重的经济负担,给社会带来严重的压力。骨质疏松是一种代谢性骨病,发生骨质疏松的病因比较复杂,目前并没有确定其明确的病因学发病机制。目前主要有以下几个方面的研究：一是遗传的因素。VDR(Vitamin D receptor)基因与骨密度相关,维生素D对骨代谢具有重要的调节作用。生长因子β(TGF-β)基因,有研究证明,TGF-β基因变异者,骨密度显著降低。二是营养及运动因素。老年人消化功能减弱,多有蛋白质、钙、微量元素等摄入不足。此外,老年人运动减少也是发生骨质疏松的重要因素。三是内分泌因素。包括性激素,降钙素以及脂肪因子等。雌激素受体(estrogen receptor, ER)在人成骨细胞和破骨细胞的存在已被证实,其基因与骨密度有一定关系。雌激素和成骨细胞和破骨细胞上的受体结合,阻止骨的再吸收。破骨细胞上有降钙素的受体,降钙素与其结合后能够抑制其细胞活性。近年研究表明,脂肪组织具有内分泌调节功能,可分泌多种细胞因子,称为脂肪因子,包括趋化素(chemerin)、瘦素(leptin)、脂联素(adiponectin)、抵抗素(resistin)等。脂肪因子不仅参与体内能量代谢、糖脂代谢,还参与炎症和免疫反应,对维持骨代谢的平衡起着重要的作用。各种原因导致的骨量减少常伴有骨髓中脂肪组织含量的增加。骨髓中脂肪组织在骨的形成和造血中发挥重要作用。从脂肪因子chemerin受体及chemerin的先后被发现,其在骨代谢中的作用,及在骨质疏松中的作用逐渐被受到重视。本实验目的是建立大鼠骨质疏松模型和股骨骨折模型,初步分析血清中脂肪因子Chemerin与骨质疏松、骨折的相关性,以期为进一步的动物实验及临床研究提供实验基础。目的：本实验通过建立大鼠骨质疏松模型及股骨骨折模型,为进一步研究脂肪因子Chemerin与骨质疏松、骨折的提供实验基础。通过分组对照,在不同时间段测定大鼠血清中Chemerin的浓度,来了解Chemerin与骨质疏松、骨折的相关性。如果证明Chemerin对骨质疏松的发病机制及骨折的恢复有调控作用,可为进一步研究其具体调控机制和治疗骨质疏松及促进骨折愈合方面开辟新的途径和治疗方法。方法：选用30只雌性Wistar大鼠,体重120-170g。大鼠按照完全随机原则分为五组,每组6只。A组为假手术(SHAM)组,B组为单纯去卵巢组(Ovariectomy, OVX), C组为单纯去卵巢雌激素治疗组(OVX+E2), D组为单纯去卵巢并股骨骨折组(OVX+FF), E组为单纯股骨骨折组(Femoral fractures, FF)。骨质疏松模型的建立采用切除卵巢方法。3月后确定骨质疏松模型建立成功后,测A组和B组血清中Chemmerin的浓度,D组和E组行股骨骨折模型的建立。股骨骨折模型的建立采用闭合骨折模型方法。建立股骨骨折模型后,分别在以后的1周、2周、4周对A、B、D、E四组大鼠血清中Chemmerin的浓度进行检测比较。确定C组骨质疏松模型建立后,给予雌激素每天5ug,连续6周,测骨密度和血清Chemerin浓度,并与B组比较。血清Chemerin浓度检测方法为酶联免疫吸附法(ELISA)。结果：卵巢切除致骨质疏松雌激素治疗组(C组)经雌激素治疗6周后与单纯去卵巢导致骨质疏松组(B组)血Chemerin浓度比较,血Chemerin浓度在两组之间无显著意义(P0.05)；卵巢切除致骨质疏松雌激素治疗组(C组)经雌激素治疗6周后,与单纯去卵巢导致骨质疏松组(B组)腰椎BMD比较,C组较B组腰椎骨密度增加,差异具有显著性(P0.05)；术后12周确定骨质疏松模型建立后,单纯去卵巢组(B组)与假手术(SHAM)组(A组)血Chemerin浓度比较,B组较A组血清Chemerin浓度增高,差异具有显著性(P0.05)；单纯股骨骨折组(E组)与假手术(SHAM)组(A组)血Chemerin浓度比较,E组较A组血清Chemerin浓度增高,差异具有显著性(P0.05),单纯去卵巢并股骨骨折组(D组)与单纯去卵巢组(B组)血Chemerin比较,D组较B组血清Chemerin浓度增高,差异具有显著性(P0.05)。结论：雌激素对血清Chemerin浓度水平无显著性影响；雌激参与了骨质疏松的病理生理过程；Chemerin参与了骨质疏松的病理生理过程；Chemerin参与了骨折的修复过程。
[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.
【学位授予单位】：长江大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R580;R683

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