铁过载对骨代谢的影响

发布时间：2018-05-09 08:12

本文选题：重型β-地中海贫血 + 骨质疏松　；参考：《广西医科大学》2015年硕士论文

【摘要】：第一部分铁过载沙鼠的骨代谢目的：探讨铁过载沙鼠骨组织的改变及骨代谢指标的变化。方法：20只雌性蒙古沙鼠随机分配为铁过载(iron overload,10)组和生理盐水(normal saline,NC)组。10组采用腹腔注射右旋糖酐铁200mg/kg/周法建立铁过载沙鼠模型。NC组沙鼠腹腔注射等量生理盐水。18周后处死沙鼠取静脉血检测铁蛋白,取骨组织行HE染色、普鲁士蓝染色、免疫组织化学染色观察各组沙鼠骨组织及碱性磷酸酶(alkaline phosphatase,ALP)、骨钙素(osteacalcin,OC)及核因子K B受体活化因子配体(receptor activator of nuclear factor kappa B ligand, RANKL)的表达。结果：铁过载组ALP、OC、RANKL的表达均高于生理盐水组,差异有统计学意义(P0.05)。结论：1.铁过载沙鼠骨骼有明显的铁沉积。2.铁过载可使骨吸收和骨形成作用都增强。第二部分骨代谢指标在广西重型β地中海贫血患者中的变化及其与铁过载的关系目的：1.调查广西β重型地贫患者铁过载发病率及严重程度。2.探讨骨代谢指标在广西重型地中海贫血患者中的变化及其与铁过载的关系。方法：2010年1月至2012年12月共收集广西多家医院血液内科250例重型β-地中海贫血患者(男160,女90,3~25岁,中位年龄8岁)和97例健康对照组(男61,女15,3~15岁,中位年龄10岁)。通过回顾性输血及排铁问卷调查收集患者年龄、性别、起始输血时间、输血量等情况,测量身高,体重,计算BMI。所有受试者检测甲状旁腺激素(parathyroid hormone, PTH), ALP, OC,血清钙,血清磷,睾酮(男性),雌二醇(女性)等生化指标。接受心铁和25(OH)D检查的患者分别为165人和192人。结果：(1)250例重型地贫患者中有246例(98.4%)患者存在铁过载,最小出现心铁沉积的患者为6岁。(2)与正常对照组比较,地贫患者血钙、25(OH)D明显下降,血磷、ALP、OC、PTH明显升高(P0.05)。(3)63(25.2%)例患者发现有低血钙症(血钙2.2mmol/L)。131(52.4%)例患者发现有高磷血症(血磷1.8mmol/L)。14(5.6%)例患者有低磷血症(P1.45mmol/L),高磷血症的患者明显较低磷血症的患者年轻(8.60±4.04vs11.57±4.57,P0.05)。26(10.4%)例患者PTH高于正常上限,14(5.6%)例患者PTH低于正常下限。≤10岁的患者PTH与年龄呈正相关(R=0.174, P0.05),10岁的患者PTH与年龄则无明显相关性(R=-0.127,P0.05)。(4)≤10岁的患者PTH与心铁值呈负相关(R=-0.212,P0.05)。(5)地贫患者的雌二醇、睾酮水平均明显降低,但与铁过载未见明显相关性。结论：1.广西重型地贫患者存在严重的铁过载。2.广西重型地贫患者血钙、25(OH)D明显降低,ALP、OC、PTH、血磷明显升高。3.未发现广西重型地贫患者血钙、25(OH)D、ALP、OC、PTH、血磷与铁过载存在直接相关性。第三部分广西重型β地中海贫血患者骨疾病发病情况及其影响因素目的：通过调查广西重型β地中海贫血患者的骨疾病发生率,并对引起骨量下降的因素与其他各国研究进行对比,提出更适合广西患者的治疗和预防方案。方法：我们研究了81例重型β-地中海贫血患者(男48,女33,4-20岁,中位年龄10岁)及101例健康年龄匹配的对照组(男61,女40,3-20岁,中位年龄10岁),详细记录病史,测量身高、体重,计算BMI。所有受试者均接受双能X线骨密度仪测定腰椎和股骨近端的骨密度(bone mass density,BMD),计算Z值(z-score=(x-mean)/SD,其中x为测量的BMD,mean为同年龄同性别正常组平均骨密度)。地贫患者还另外抽血进行下列检测：A)血清铁蛋白,心脏铁；B)甲状旁腺激素(PTH);C)骨形成指标：碱性磷酸酶(ALP),骨钙素(0C)；D)血清钙,血清磷；E)男性睾酮,女性雌二醇等检查。结果：34(41.98%)例患者有身材矮小,25(30.86%)例患者低体重,74(91.36%)例患者低体重指数(BMI18.5)。地贫患者骨疾病发病相当普遍。在81例患者中,8(9.76%)例患者骨质疏松,23(28.4%)例患者骨量减少。地贫患者骨质疏松最早发生在5岁,骨量减少最早发生在4岁。未发现铁蛋白、T2*值与骨密度及Z值有直接相关性(P0.05)。证实了患者BMD与年龄呈正性相关,Z值与年龄呈负相关(P0.05),但不同年龄分组骨疾病的发病率并未见明显差异(P0.05)。相对于正常骨量患者,骨质疏松患者血钙明显降低,ALP、PTH明显升高(P0.05)。睾酮、雌激素与骨量或Z值存在正相关性(P0.05)。结论：重型地贫患者建议从4岁开始早期规律检测骨密度,注意电解质的变化,早期补充钙剂或维生素D,补充性激素,提高成年后生存质量,防治骨质疏松造成的痛苦及残疾。
[Abstract]:The first part of the iron overload gerbil bone metabolism Objective: To explore the changes of bone tissue and the changes of bone metabolism index in iron overload gerbils. Methods: 20 female Mongolia gerbil were randomly assigned to iron overload (iron overload, 10) and normal saline (normal saline, NC) group.10 group by abdominal cavity injection of dextran 200mg/kg/ week method to establish iron overload The gerbil group.NC group of gerbil was injected with the same amount of normal saline for.18 weeks to detect the ferritin, the bone tissue was stained with HE, Prussian blue staining, and immunohistochemical staining was used to observe the bone tissue and alkaline phosphatase (alkaline phosphatase, ALP), osteocalcin (osteacalcin, OC) and the activation cause of K B receptor of nuclear factor in each group. The expression of the sub ligand (receptor activator of nuclear factor kappa B ligand, RANKL). Results: the expression of ALP, OC, RANKL were higher than that of the normal saline group, and the difference was statistically significant. Conclusion: the iron overload of 1. iron overload gerbils has an obvious iron deposition. The iron overload can enhance the bone absorption and bone formation. The second part of the iron overload can enhance the bone absorption and bone formation. Changes in bone metabolism and the relationship with iron overload in patients with severe beta thalassemia in Guangxi: 1. investigate the incidence and severity of iron overload in patients with severe poverty in Guangxi beta.2. to explore the changes in bone metabolism index in patients with severe thalassemia in Guangxi and the relationship with iron overload. Methods: from January 2010 to 2012 1 In February, 250 patients with severe beta thalassemia (160 men, 90,3~25 years old, middle age 8 years old) and 97 healthy control groups were collected in the Department of Hematology in Guangxi, and 97 healthy controls (male 61, female 15,3~15 years old and 10 years old). The age, sex, starting time of blood transfusion, blood transfusion and so on were collected and measured by a retrospective blood transfusion and iron drainage questionnaire survey. Weight, all BMI. subjects were calculated to detect parathyroid hormone (parathyroid hormone, PTH), ALP, OC, serum calcium, serum phosphorus, testosterone (male), estradiol (female) and other biochemical indexes. The patients receiving heart iron and 25 (OH) D examination were 165 and 192. Results: (1) 250 cases of severe poor patients (98.4%) had iron overload. The patients with minimal cardiac iron deposition were 6 years old. (2) compared with the normal control group, blood calcium, 25 (OH) D decreased significantly, blood phosphorus, ALP, OC, PTH significantly increased (P0.05). (3) 63 (25.2%) patients found hypocalcemia (blood calcium 2.2mmol/L).131 (52.4%) patients found to have hyperphosphatemia (blood phosphorus 1.8mmol/L).14 (5.6%) patients with hypophosphoremia (P1) (P1) .45mmol/L), patients with hyperphosphatemia were significantly younger (8.60 + 4.04vs11.57 + 4.57, P0.05).26 (10.4%).26 (10.4%) patients higher than normal upper limit, 14 (5.6%) patients with PTH lower than normal lower limit. PTH in patients younger than 10 years was positively correlated with age (R=0.174, P0.05), 10 year old patients had no significant correlation with age (R=-0.127, P0.05). (4) there was a negative correlation between PTH and the value of heart iron (R=-0.212, P0.05). (5) the levels of estradiol and testosterone in the poor patients were significantly decreased, but no significant correlation was found between iron overload and iron overload. Conclusion: 1. severe iron overload in Guangxi severe poor patients with severe iron overload in Guangxi severe poor patients with blood calcium, 25 (OH) D, ALP, OC, PTH, blood phosphorus obviously rise High.3. was not found in Guangxi severe poor patients with blood calcium, 25 (OH) D, ALP, OC, PTH, and there was a direct correlation between blood phosphorus and iron overload. Third the incidence of bone disease and its influencing factors in patients with severe beta thalassemia in Guangxi were investigated by investigating the incidence of bone disease in patients with severe beta thalassemia in Guangxi and the decrease of bone mass. The factors were compared with other countries to propose a more suitable treatment and prevention scheme for Guangxi patients. Methods: We studied 81 patients with severe beta thalassemia (male 48, female 33,4-20 years, middle age 10 years old) and 101 healthy age matched control groups (male 61, female 40,3-20 years, middle age 10 years old), and recorded the history of the disease in detail and measured the body. High, weight, and calculated BMI. all subjects received the dual energy X-ray bone densitometer to determine the bone mineral density (bone mass density, BMD) of the lumbar and proximal femur (BMD), and calculated the Z value (z-score= (x-mean) /SD, X was BMD, mean was the average bone density in the same age group of same sex). White, heart iron; B) parathyroid hormone (PTH); C) bone formation indicators: alkaline phosphatase (ALP), osteocalcin (0C); D) serum calcium, serum phosphorus; E) male testosterone, female estradiol and other tests. Results: 34 (41.98%) patients had short stature, 25 (30.86%) patients with low weight, 74 (91.36%) patients with low body mass index (BMI18.5). Bone disease of the poor patients. Among 81 patients, 8 (9.76%) patients had osteoporosis and 23 (28.4%) patients had reduced bone mass. The first occurrence of osteoporosis in the poor patients was 5 years old, and the earliest osteopenia occurred at 4 years. No ferritin was found. The T2* value had a direct correlation with bone density and Z value (P0.05). It was confirmed that the patient BMD was positively related to age, Z value and Age was negatively correlated (P0.05), but there was no significant difference in the incidence of bone disease in different age groups (P0.05). Compared with normal bone mass, blood calcium decreased significantly in osteoporotic patients, ALP, PTH increased significantly (P0.05). Testosterone, estrogen and bone mass or Z were positively correlated (P0.05). Conclusion: severe poor patients are recommended to begin early from 4 years of age. Regular detection of bone density, attention to the changes in electrolytes, early supplement of calcium or vitamin D, supplemental sex hormones, improve the quality of life after adult, the prevention and treatment of osteoporosis caused by pain and disability.

【学位授予单位】：广西医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R556.61;R580

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