长期多代饮奶近交BALB/C小鼠的骨代谢模型

背景:现有的研究结果大多是反映短期饮奶或单代饮奶对骨代谢的影响,而反映长期多代饮奶对骨代谢影响的研究较少.目的:观察长期多代饮奶对近交BALB/C小鼠骨代谢的影响.设计、时间及地点:完全随机设计,实验于2005-03/2006-03在郑州大学公共卫生学院实验室完成.材料:取4周龄近交BALB/C小鼠60只,雌雄各半,随机分为实验组和对照组,每组30只.红星牌全脂甜奶粉由黑龙江红星集团股份有限公司生产(批号20050412),每7.43 g加入13 mL烧开的去离子水,还原为浓缩4倍的牛奶.方法:实验组每日给予牛奶灌胃(0.083mL/g体质量),对照组每日给予相同剂量去离了水灌胃,连续灌胃6周.到小鼠发情期(约70 d左右)后,同组小鼠雌雄合笼交配,交配成功后将雌性小鼠分笼喂养,直到产下第2代.第2代小鼠到断奶期时(3周左右)断母乳,各组第2代继续分别用牛奶和去离子水灌胃,重复上述步骤得到第3代,断母乳后继续用牛奶和去离子水灌胃,第3代出生后17周左右实验结束.主要观察指标:每代在其子代出生后1个月,每组取20 只剪尾取血,采用全血干化学免疫浓缩法测定特异性骨碱性磷酸酶活性;3 d后再去眼球取血,离心取血清,采用邻甲酚肽络合酮比色法(终点法)测定血清钙浓度和血清碱性磷酸酶活性.采用磷钼酸比色法测定血清磷质量浓度.采用放射免疫分析法测定血清骨钙素质量浓度.结果:①血清钙、磷水平:实验组各代之间、对照组各代之间、各代中实验组和对照组之间,差异均无显著性意义(P>0.05).②血清碱性磷酸酶活性:第3代实验组碱性磷酸酶活性低于对照组(P<0.05).实验组第3代碱性磷酸酶活性低于前2代(P<0.05).③特异性骨碱性磷酸酶活性:第2代、第3代实验组特异性骨碱性磷酸酶活性低于对照组(P<0.05).实验组第3代的特异性骨碱性磷酸酶活性低于第1代(P<0.05).④血清骨钙素水平:在实验组3代之间有明显升高趋势,每两代之间差异均有显著性意义(P<0.05).第2代、第3代实验组骨钙素质量浓度高于对照组(P<0.05).结论:长期多代饮奶可增强BALB/C小鼠成骨细胞活性,促进骨骼生长发育.     

不同负荷游泳运动对老龄雄性小鼠骨代谢水平的影响

目的　探讨不同负荷游泳运动对老龄雄性小鼠骨代谢水平的影响。方法　以 12月龄 (老龄 )雄性小鼠为研究对象 ,分为 3 0min组、60min组、60min 负重组、实验对照组及安静对照组 ,观察增龄及不同负荷游泳运动对老龄雄性小鼠腰椎骨、股骨胶原含量 (HOP)、血清性激素 (T ,E2 )、骨钙素、碱性磷酸酶及钙含量的影响。结果　当实验进行 8周后 ,60min组、60min 负重组小鼠的血清睾酮 ( 5 7.82 6± 13 .999ng/dl ,5 8.985± 12 .3 0 1ng/dl)、雌二醇 ( 3 0 .81± 4.14pg/ml ,3 2 .62± 5 .85pg/ml)水平及股骨羟脯氨酸含量 ( 12 .5 4± 0 .89μg/mg ,13 .47± 0 .84μg/mg)均显著高于对照组 (T :43 .3 3 7± 13 .946ng/dl,E2 :2 2 .3 2± 4.2 1pg/ml ,HOP :11.92± 1.0 7μg/mg ,均P <0 .0 5 )。结论　适宜负荷的游泳运动可减缓伴随增龄而发生的性激素水平降低及骨胶原丢失 ;而且该作用在较大负荷的游泳运动中表现得尤为明显     

复方片仔癀肝宝对乙醇代谢的影响

目的：探讨复方片仔癀肝宝对乙醇代谢的影响。方法：SD雄性大鼠随机分为正常对照组、模型组、海王金樽组(阳性对照)和复方片仔癀肝宝高、中、低剂量组,每组8只。给药后0.5 h除了正常对照组,其余各组灌胃白酒。采用顶空气质联用法(HS-GC-MS)测定给酒后0.5、1、2、3、5 h大鼠血液中的乙醇浓度。结果：复方片仔癀肝宝组在不同时间点大鼠血液中的乙醇浓度均低于模型组(P<0.05)。结论：复方片仔癀肝宝促进乙醇代谢,达到解酒的目的。     

复方片仔癀肝宝对乙醇代谢的影响

目的:探讨复方片仔癀肝宝对乙醇代谢的影响。方法:SD雄性大鼠随机分为正常对照组、模型组、海王金樽组(阳性对照)和复方片仔癀肝宝高、中、低剂量组,每组8只。给药后0.5 h除了正常对照组,其余各组灌胃白酒。采用顶空气质联用法(HS-GC-MS)测定给酒后0.5、1、2、3、5 h大鼠血液中的乙醇浓度,运用ELISA法检测乙醇达到峰值时乙醇脱氢酶和乙醛脱氢酶的含量。结果:复方片仔癀肝宝组在不同时间点大鼠血液中的乙醇、乙醇脱氢酶和乙醛脱氢酶的浓度均低于模型组(P0.05)。结论:复方片仔癀肝宝促进乙醇代谢,达到解酒的目的。     

阿仑膦酸钠对大鼠松质骨和密质骨影响的比较

目的：比较阿仑膦酸钠(固邦，ALN)对去卵巢大鼠胫骨上段和腰椎质松骨及胫骨中段密质骨的影响。方法：3月龄雌性SD大鼠，ALN1mg／(kg&;#183;d)，灌胃给药90d。骨标本行不脱钙骨制片，骨组织形态计量法钡5量。结果：松质骨：OVX组胫骨上段(PTM)和腰椎(LV)质松骨的骨量减少(P&;lt;0．001)，骨结构变差；ALN组PTM，LV骨量增加(P&;lt;0．001)，完全对抗OVX大鼠的骨高转换。密质骨：OVX组胫骨中段(TX)骨量减少(P&;lt;0．05)，骨内膜骨形成和骨吸收增加。ALN组骨量增加(P&;lt;0．05)，骨内膜骨形成减少而骨吸收有减少的趋势。结论：ALN能有效预防OVX后大鼠的骨质疏松，但不同部位有不同的骨转换速度。     

松质骨,皮质骨对微孔涂层植入物生物学固定的影响

目的 比较微孔涂层植入物在松质骨、皮质骨内生物学固定界面剪切应力强度极限及界面疲劳损伤规律,探讨两种不同的骨组织对微孔涂层植入物生物学固定的影响。方法 将标准的钛合金微孔涂层金属试件植入犬股骨上段,试件上１／２端位于粗隆部的松质骨内,下１／２端位于股骨的皮质骨内。测定松质骨段、皮质骨段植入生物学固定界面剪切应力强度极限及用扫描电镜（ＫＥＭ）疲劳台观察疲劳损伤规律。结果 松质骨内植入物生物学固定界面     

运动负荷骤降对生长期大鼠长骨骨量和骨代谢生化指标的影响

目的观察运动负荷骤降对生长期大鼠长骨骨量(BMC)、骨密度(BMD)和骨代谢生化指标的影响。方法雄性3月龄SD大鼠48只,随机分成大强度运动组(T1)、大强度转低强度运动组(T2)、低强度运动组(T3)、对照组(Con),每组12只。前6周,T1、T2组进行大强度跑台运动,T3组进行低强度跑台运动。6周末,DEXA测定每组部分大鼠股骨BMC、BMD,酶标仪法测定血清碱性磷酸酶(ALP)、骨钙素(BGP)和抗酒石酸性磷酸酶(TRACP5b)。降低T2组运动负荷,与T3组一致,其余组运动强度不变,继续运动6周。同样方法测定上述指标。结果与运动负荷降低前比较,12周末T2组大鼠ALP、BGP降低(P<0.05),TRACP5b升高(P<0.05),股骨BMC、BMD无显著性差异(P>0.05)。结论运动负荷骤降使成长期大鼠长骨骨形成抑制,骨吸收增强。     

高脂饮食对小鼠脂代谢和矿物元素代谢的影响

目的:观察高脂饮食对小鼠脂代谢和肝脏矿物元素代谢的影响。方法:实验于2005-01/07在广东医学院生理教研室实验室完成。选择昆明种雄性小鼠66只,随机数字表法分为普通饲料组和高脂饲料组,各33只,分别喂养普通饲料和高脂饲料(3%胆固醇、10%猪油、87%基础饲料混合),各组动物分别在喂养16,32,64d时各抽取11只,禁食水12h眼眶取血后处死。总胆固醇测定采用CHOD-PAP终点比色法;剥离腹腔脂肪用万分之一天平称湿质量;取新鲜肝组织采用火焰原子吸收光谱法测定锌、铜、铁、钙、镁、锰含量。结果:纳入小鼠66只,均进入结果分析。①高脂饲料组在喂养16,32,64d时血清总胆固醇含量和腹腔脂肪质量都明显高于普通饲料组[喂养16d分别为(6.34±1.38),(3.61±0.65)mmol/L;(1.58±0.28),(1.12±0.28)g;喂养32d分别为(4.89±0.88),(3.16±0.63)mmol/L;(2.20±0.65),(1.52±0.30)g;喂养64d分别为(5.82±0.51),(4.56±1.28)mmol/L;(3.35±1.17),(1.99±0.79)g,P<0.01]。②喂养16d时高脂饲料组小鼠肝脏锌、铜、镁含量低于普通饲料组[分别为(32.95±8.80),(43.10±8.07)μg/g;(9.21±1.20),(10.59±1.63)μg/g;(244.24±27.32),(304.37±77.88)μg/g,P<0.05];喂养32d时高脂饲料组小鼠肝脏钙、铜、铁含量低于普通饲料组[分别为(299.51±24.74),(457.54±65.92)μg/g,P<0.01;(8.62±1.41),(10.19±1.08)μg/g,P<0.01;(30.07±9.14),(39.49±6.73)μg/g,P<0.05];喂养64d时高脂饲料组小鼠肝脏铜、铁、锌、钙、镁含量低于普通饲料组[分别为(8.61±1.66),(9.50±0.41)μg/g;(35.36±10.01),(50.80±11.27)μg/g,P<0.01;(37.24±6.89),(43.68±6.86)μg/g;(335.43±51.66),(381.68±50.94)μg/g;(209.33±41.66),(259.14±49.86)μg/g,P<0.05]。结论:高脂饮食引起脂代谢紊乱早期伴有轻度矿物元素代谢改变,持续高脂饮食,脂代谢紊乱进一步发展,并伴有显著的矿物元素代谢紊乱。     

长期摄入不同剂量乙醇对大鼠骨骼肌G11 α表达及胰岛素抵抗的影响

目的：观察G蛋白家族中G11α和Gqα mRNA在乙醇诱导下对大鼠骨骼肌胰岛素抵抗的作用.方法：①实验于2003-09/2005-03在山东省立医院中心实验室完成.选用雄性Wistar健康成年大鼠40只.随机将大鼠分为4组,对照组、大剂量饮酒组、中剂量饮酒组、小剂量饮酒组,每组10只.对照组：胃管灌注蒸馏水5.0 g/（kg&;#183;d）,1次/d;大、中、小剂量饮酒组：胃管灌注乙醇量5.0,2.5,0.5g/（kg&;#183;d）,1次/d,每组均喂养5个月.②采用强生血糖仪测定空腹血糖和糖负荷后2 h血糖.③采用液体闪烁计数仪分别测量基础状态下、胰岛素刺激后的组织非特异吸收的2-D-3H葡萄糖量.基础状态葡萄糖摄取=单位重量基础状态肌肉计数-单位重量煮沸变性肌肉计数;胰岛素刺激后葡萄糖摄取=单位重量胰岛素刺激后肌肉计数-单位重量基础状态肌肉计数.④采用反转录聚合酶链反应法测定G11α和Gqα mRNA水平.采用蛋白质印迹实验测定G11α和Gqα蛋白水平.⑤各组间比较采用单因素方差分析.结果：大鼠40只均进入结果分析.①各饮酒组大鼠空腹血糖和糖负荷后2 h血糖与对照组相近.②大、中剂量饮酒组大鼠基础状态骨骼肌糖摄取量与对照组比较,分别下降29%,72%（P＜0.05）;胰岛素刺激后,分别下降27%,61%（P＜0.05）;小剂量饮酒组大鼠无明显变化.③大、中、小剂量饮酒组大鼠骨骼肌G11α mRNA表达与对照组比较,分别下降57%,42%,38%（P＜0.05～0.01）;Gqα mRNA表达无明显变化.④大鼠长期摄入乙醇后骨骼肌G11α和Gqα蛋白水平变化与mRNA水平变化趋势一致.结论：①乙醇喂养5个月后,大鼠机体水平上没有表现出明显的糖代谢紊乱.②摄入乙醇剂量为5.0 g/（kg&;#183;d）和2.5 g/（kg&;#183;d）5个月后,大鼠骨骼肌产生明显的胰岛素抵抗.③长期摄入乙醇可影响大鼠骨骼肌G11α表达,并呈剂量依赖性.④各饮酒组大鼠骨骼肌Gq α mRNA表达及其蛋白水平变化不明显.     

Alterations of lipid metabolism in healthy volunteers during long-term ethanol intake

Nine young, healthy male volunteers were given ethanol (75 g/day) for 5 weeks. The ethanol was divided into five daily doses and taken so that blood ethanol levels never exceeded 0.04% (w/v). During the latter part of the ethanol intake period, there was a significant, transient increase of plasma triglyceride (TG) concentrations followed by reduction to normal levels. A three-fold increase of lipoprotein lipase activity (LLA) occurred in biopsy specimens of adipose tissue. An increase of alpha-lipoprotein concentrations, which correlated significantly with the decrease in plasma TG levels and the increase in adipose LLA, was also observed during the ethanol intake period. No changes were observed in plasma cholesterol and beta-lipoprotein levels. A transient, three-fold increase of TG concentrations occurred in liver biopsy specimens. Ultrastructural and cytochemical examinations of the biopsy specimens showed hyperplasia of the smooth endoplasmic reticulum, and increased canallicular activity of gamma-glutamyl transferase (gamma-GT) activity in most subjects towards the end of and after the ethanol intake period. Serum gamma-GT levels also increased significantly.     

阿仑膦酸钠对大鼠松质骨和密质骨影响的比较

目的:比较阿仑膦酸钠(固邦,ALN)对去卵巢大鼠胫骨上段和腰椎质松骨及胫骨中段密质骨的影响。方法:3月龄雌性SD大鼠,ALN1mg/(kg·d),灌胃给药90d。骨标本行不脱钙骨制片,骨组织形态计量法测量。结果:松质骨:OVX组胫骨上段(PTM)和腰椎(LV)质松骨的骨量减少(P<0.001),骨结构变差;ALN组PTM,LV骨量增加(P<0.001),完全对抗OVX大鼠的骨高转换。密质骨:OVX组胫骨中段(TX)骨量减少(P<0.05),骨内膜骨形成和骨吸收增加。ALN组骨量增加(P<0.05),骨内膜骨形成减少而骨吸收有减少的趋势。结论:ALN能有效预防OVX后大鼠的骨质疏松,但不同部位有不同的骨转换速度。     

长期吸入糖皮质激素的哮喘患者对骨密度和骨代谢的影响

目的探讨中国(主要是南京地区)成人哮喘患者吸入糖皮质激素(glucocorticoid,GC)后的骨代谢和骨密度变化,了解中国哮喘患者长期吸入GC是否有引起骨质丢失的可能以及其与吸入GC剂量的关系。方法采用双能X线骨密度仪(DXA)分别测定了20例每日坚持吸入GC大于等于5个月和20例与之配对的未使用GC的哮喘患者的脊椎骨(L2～4)、股骨颈、股骨粗隆、股骨三角及股骨总量的骨密度(BMD),同时用放免法等测定这些患者的血骨钙素(BGP)以及碱性磷酸酶(AKP)等指标,进行对比分析。结果两组患者的5处绝对BMD和相对BMD(与同年龄、性别相应正常值的百分比)、BGP、AKP等各指标之间比较无显著差异(r=1.70～0.21,P>0.05);吸入组每日吸入GC>400μg者与≤400μg者、与对照组之间的上述各指标比较无显著差异(r=-1.60～0.41,P>0.05);吸入组累积吸入GC>120000μg者与≤120000μg者、对照组之间的上述各指标比较除脊椎骨外余均无显著差异(r=2.24,P>0.05);吸入组与对照组中年龄≥45岁者的上述各指标之间的比较未显示差异。吸入组患者5处绝对BMD与其相应日均吸入GC量之间未呈现明显的相关性,P值均>0.05,但脊椎骨、股骨颈和股骨三角的BMD与GC累积量之间的r=-0.50、-0.52和-0.53,P值均<0.05。不过,吸入组5处BMD的相对百分比和T评分与其GC累积     

Effects of cadmium intake on bone metabolism of mothers during pregnancy and lactation

Cadmium (Cd) is a heavy metal that exists ubiquitously in the environment, and it interacts with essential elements such as zinc, copper, iron, and calcium (Ca). Particularly, Cd interferes with Ca and vitamin D metabolism in bone kidney and intestine. The interaction between Cd and Ca in bone, intestine, and kidney may result in the disorder of bone metabolism. On the other hand, pregnancy and lactation are also important physiological factors affecting bone metabolism in the mother. Ca absorption is decreased by competition with Cd in the intestine, and more Ca is released from maternal bone and transferred to neonate by lactation. In the intestine, Cd uptake competes with Ca uptake. Cd causes a marked decrease in bone density compared to the normal decrease in bone mineral density during lactation. Lactation is an important factor contributing to the decrease in bone mineral density and Cd has an additive effect of decreasing bone metabolism of mother animal, although the Cd intake level is relatively low (approximately 3-14 microgCd/kg/day). The relationship among maternal Cd intake, renal function and bone metabolism and the interaction between Cd and Ca during lactation are reviewed herein, together with additional data obtained recently in our laboratory.     

The effect of the steroid-sparing response to low-dose methotrexate on bone metabolism in glucocorticoid-dependent asthmatics

BACKGROUND: The skeletal effects of low-dose methotrexate (MTX), in glucocorticoid-dependent asthmatics (GCDA), are unknown. METHODS: We studied 9 patients from a total of 26 chronic GCDA who completed 28 weeks of MTX (15 mg weekly, intramuscularly). Prednisolone dose was not altered during the first 12 weeks, and was then reduced between 12 and 28 weeks. Mean (S.E.M.) age of the patients was 54 (4.0) years. They had normal bone mineral density (BMD), were not taking medication that affected bone metabolism (except prednisolone and inhaled corticosteroids) and all achieved at least 50% reduction in prednisolone dose at 28 weeks. Blood and urine samples were obtained at baseline, 12, 28 and 40 weeks for measurement of serum osteocalcin (OC) and bone alkaline phosphatase (Bone-ALP) as formation markers and urinary deoxypyridinoline (DPD) and N-terminal cross-linked telopeptide of type I collagen (NTX-I) as resorption markers. RESULTS: Concurrently with the changes in prednisolone dosage serum OC levels increased significantly at 28 weeks (p<0.008) (8.1+/-1.0 ng/ml) compared to baseline (4.7+/-0.6 ng/ml) and 12 weeks (5.1+/-0.6 ng/ml), but trended back by 40 weeks (6.6+/-0.6 ng/ml). No significant changes were observed for the other bone markers between baseline and the other time points. CONCLUSIONS: The beneficial effects of steroid reduction on bone metabolism do not appear to be impaired by concomitant MTX treatment at least over 12 weeks.     

钙干预对儿童生长性骨痛骨代谢和骨密度的影响

目的 通过对确诊为生长性骨痛的儿童进行钙干预,探讨其补充钙的效果.方法 将160例患儿随机分为补钙组、对照组,不同时点记录生长痛症状缓解情况,腰椎骨密度( L1～4 BMD)、骨代谢生化指标血bALP、尿Ca、血Ca的变化.结果 生长性骨痛的儿童钙干预后,1 a内骨痛症状有效缓解,而且无复发;补钙后其骨释放减少;自身L1～4 BMD提高;血钙值无统计学差异;补钙组尿钙排出量不变,对照组尿钙排出量减少且低予实验组.结论 生长性骨痛的儿童适当补充钙,对其症状的缓解和骨骼的发育有较好的作用.     

Effects of low-dose cyclosporine prophylaxis in nonobese diabetic mice

Among female nonobese diabetic mice, ketotic insulin-dependent diabetes mellitus (IDDM) develops spontaneously in 80% between 12 and 26 weeks of age. This condition resembles human type I diabetes. IDDM developed in 0 of 11 (0%) mice prophylactically treated with 10 mg of cyclosporine A (CyA) per kg s.c. every 4th day from 8 to 26 weeks of age; 8 of 10 (80%) of sex- and age-matched controls developed IDDM; 2 of 8 (25%) followed up to 5 months beyond the time of drug administration developed IDDM. The distribution of specific radioactivity ([3H]CyA) was used to calculate the concentrations of CyA in serum, blood cells and various organs. Serum values of CyA produced by radioimmunoassay were higher than those estimated by the [3H]CyA method. Pancreata of CyA-treated mice were histologically normal. Pancreata of control mice showed lymphocytic infiltration of the islets of Langerhans. Neither hepatotoxicity nor nephrotoxicity assessed by biochemical and histological data was detectable in CyA-treated mice. The insulin secretory capacity of trypan blue viable functional pancreatic islets isolated post-treatment; was significantly lower in controls than in CyA-treated mice; islet content of insulin was not statistically different between controls and CyA-treated mice. We conclude that low nontoxic doses of CyA abrogate completely the development of diabetes in the female nonobese diabetic mouse and abolish lymphocytic infiltration of the islets of Langerhans against which there is autoimmunity. The effect of CyA persists well past the duration of therapy.