糖代谢与骨代谢相互作用的研究进展

临床上糖尿病患者骨折风险明显升高,同时骨代谢异常的患者也往往伴随葡萄糖不耐受和胰岛素抵抗,近年来多方研究表明糖代谢与骨代谢之间存在复杂的相互作用,本文综述了二者之间相互作用的研究现状及相关进展.     

The investigation of glucose metabolism and insulin secretion in subjects of chronic hepatitis B with cirrhosis

Aims: To investigate the situations of abnormal glucose metabolism and dysfunction of pancreatic islet beta cells in subjects of chronic hepatitis B (CHB) with cirrhosis. Methods: 106 hepatitis B virus (HBV) positive subjects with liver cirrhosis as well as with different grade of Child-Pugh and 37 healthy subjects were included in this study. The oral glucose tolerance test (OGTT), C-peptide and insulin release test were detected. Plasma glucose and insulin levels were analyzed periodically for 2 h after oral glucose loading. Results: There was no significant difference in the level of fasting plasma glucose and C-peptide between cirrhosis group and control group (P>0.05). The levels of OGTT 2 h glucose, insulin and C peptide were significantly higher in cirrhosis group than control group (P<0.01). Peak plasma glucose levels were obtained at 60 min in normal group and cirrhosis group. The peak insulin and C-peptide response occurred at 60 min in normal group, whereas it was delayed to 120 min in cirrhosis group. There was a significant difference between two groups in the pattern of plasma glucose levels at corresponding time points (P<0.05). The OGTT 2 h glucose and insulin levels were positively correlated with Child-Pugh Score (r1 = 0.389, r2 = 0.508, P<0.01). Conclusion: These findings implied that there was a certain degree of insulin resistance and abnormal glucose metabolism in the patients with liver cirrhosis.     

Evaluation of the osseointegration of dental implants coated with calcium carbonate:an animal study

In an attempt to overcome the limitations of titanium in dental and orthopaedic clinical applications, a new method has been developed to prepare calcium carbonate coatings on sandblasted and acid-etched (SA) titanium implants. The purpose of this study was to investigate the effect of calcium carbonate-SA (CC-SA) implants on osseointegration in vivo. The surfaces of SA and CC-SA implants were characterised for surface morphology and surface chemistry. Subsequently, these two kinds of implants were implanted in the femoral condyles of rabbits. The implants were retrieved and prepared for histological and histomorphometric evaluation 1, 2, 4, 8 and 12 weeks after implantation. Significantly higher values of bone-to-implant contact of the entire implant except the gap area (BIC_ALL) and the bone-to-implant contact of the gap area (BIC_GAP) were found in animals with the CC-SA implants than in those with the SA implants at 4 weeks. Higher values of total gap bone were found in those with the CC-SA implants than in those with the SA implants at 1, 2 and 4 weeks. In conclusion, the current findings demonstrate that the calcium carbonate coating can improve and accelerate the early ingrowth of bone and osseointegration at the early healing phase. This may reduce clinical healing times and thus improve implant success rates.     

经玻璃紫外线照射对大鼠25-羟维生素D水平及骨代谢的影响

目的：目前研究发现B型紫外线照射与血清25-羟维生素D［25-hydroxy vitamin D, 25-（OH）D］水平有剂量-效应关系,并且维生素D与骨代谢相关。该研究探讨经玻璃紫外线照射对大鼠25-（OH）D及骨代谢的影响。方法：选用30只Wistar大鼠建立不同紫外线暴露方式的动物模型,饲以缺乏维生素D饮料,随机分为避光组,紫外线直接照射160 min组,简称直射组,紫外线经单层玻璃照射160 min组,简称经玻组。每组各10例。21 d实验结束时,测定各组大鼠血清25-(OH) D、甲状旁腺激素(parathyroid hormone, PTH)、骨碱性磷酸酶(bone alkaline phosphatase, BALP)、骨钙素(osteocalcin, OC)和骨Ⅰ型胶原羧基末端肽(carboxyterminal cross-linked telopeptide of type I collagen, ICTP)的浓度及骨密度(bone mieral density, BMD)。结果：经玻组骨密度（BMD）为0.036±0.002 g/cm2,显著高于避光组(P<0.01); ICTP浓度0.181±0.067 μg/L,显著低于避光组(P<0.01);PTH、25-（OH）D、BALP及OC浓度分别为3.72±0.38 pg/mL、28.67±1.35 nmol/L、25.03±4.65 μg/mL和0.559±0.067 ng/mL,与避光组差异无显著性（P>0.05）。 经玻组BALP和ICTP水平及BMD与直射组差异无显著性(P>0.05);OC和PTH浓度显著高于直射组(P<0.05);25-（OH）D水平显著低于直射组（P<0.01）。结论：经单层玻璃的紫外线照射不能显著提高血浆25-（OH）D水平,但可降低维生素D缺乏造成的骨转化率升高并提高骨密度,与直接紫外线照射达到相似效果。［中国当代儿科杂志,2009,11（2）：138-141］     

哮喘患儿吸入糖皮质激素对骨代谢影响

目的　探讨哮喘患儿吸入糖皮质激素 (IGs)对骨代谢影响。方法　对 5 0例 5～ 12岁连续吸入IGs 2年哮喘患儿 ,于吸入前 ,0 .5、1、1.5、2年分次进行血清钙、磷、骨源性碱性磷酸酶 (BALP)、骨钙素 (OC)水平监测 ,并进行身高生长速度测定。其中观察I组 2 7例 ,平均吸入丙酸倍氯米松 2 5 0 μg/d ;观察Ⅱ组 2 3例 ,平均吸入丙酸氟替卡松 15 0 μg/d ;正常对照组 2 2例。 结果　观察Ⅰ、Ⅱ组、对照组间分次检测的血钙、磷、BALP、OC水平均无显著差异 (P均 >0 .0 5 ) ;且各组间q检验无显著差异 (P均 >0 .0 5 )。观察Ⅰ、Ⅱ组身高生长速度分别于对照组比较 ,均无显著差异 (P均 >0 .0 5 )。结论　每日小剂量较长时间IGs对儿童骨生长发育无明显影响。     

肥胖男童骨密度变化与骨代谢指标及胰岛素抵抗的关系探讨

目的 探讨单纯性肥胖男童骨密度变化与骨代谢生化指标及胰岛素抵抗之间的关系,以了解肥胖男童骨代谢异常可能的发病机制.方法 应用定量骨密度超声仪测定70例7～14岁小同体质指数(BMI≥23)的肥胖男童及20例年龄、性别匹配的健康男童的桡骨远端的超声传播速度(SOS),对其骨骼矿物质密度(BMD)进行评价.并对其空腹血钙(Ca)、磷(P)、碱性磷酸酶(ALP)、血糖(FBG)、胰岛素(FINS)、骨钙素(OC)、甲状旁腺素(PTH)进行监测.用稳态模式(HOMA)计算胰岛素抵抗指数(IR=FBG×FINS/22.5)、胰岛β细胞分泌指数[IS=20×FINs/(FBG-3.5)1.结果 BMI≥25的肥胖男童BMD、OC明显低于正常对照组(P<0.01),而FBG、FINS、HOMA-IR、DTH、ALP均显著高于正常对照组(P<0.01);经双变量相关分析,BMD分别与BMI、FINS及HOMA-IR呈负相关(r=-0.50,r5=-0.58、-0.60,P均<0.01),与OC呈正相关(r=0.63,P<0.01).结论 严重肥胖男童存在明显的骨代谢异常,且与肥胖程度、高胰岛素血症和胰岛素抵抗密切相关.     

Intracellular localization of the Menkes and Wilson's disease proteins and their role in intracellular copper transport

Copper is a heavy metal ion essential for the activity of a variety of enzymes in the body. In excess, copper is a very toxic ion and therefore efficient regulation of its metabolism is required. This is dramatically illustrated by the genetic disorders X-linked Menkes disease and autosomal recessive Wilson's disease. In 1993, both the Menkes and Wilson's genes were isolated and it was found that these genes encode homologous cation copper transporting P-type ATPase proteins. The Menkes protein (ATP7A) is expressed in most tissues, except liver. In contrast, the Wilson's protein (ATP7B) is abundantly expressed in liver. Intracellular localization of those proteins was investigated. Both ATP7A and ATP7B are localized in the trans-Golgi network and post-Golgi vesicular compartment (PGVC) in the cell. This intracellular localization was altered by the copper content present in the cell. This result may support the hypothesis that ATP7A and ATP7B are involved in cellular copper transport and those proteins could be suitable models for elucidating intracellular copper metabolism.     

尼莫地平对法洛四联症患儿心肌细胞内钙运转及心功能的影响

目的　研究尼莫地平对法洛四联症（ＴＯＦ）患儿心肌细胞钙转运和心功能的影响。方法　２７ 例ＴＯＦ分为对照组（１２例）和治疗组〔１５ 例,尼莫地平１．０～１．５ｍ ｇ／（ｋｇ·ｄ）×１４ｄ〕。测定治疗前后心肌细胞内外钙浓度和心功能。结果　用尼莫地平后治疗组红细胞游离钙和总钙浓度明显降低,钠泵活性升高,而钙泵活性无变化;心肌细胞游离钙（２０４±３３ｎｍ ｏｌ／Ｌ）较对照组（３４７±８５ｎｍ ｏｌ／Ｌ）明显降低（Ｐ＜ ０．０１）;心肌细胞线粒体和内质网肿胀明显减轻或消失,线粒体密度升高;心脏指数和左右心室充盈功能明显改善。结论　尼莫地平可明显减轻ＴＯＦ患儿心肌细胞内外的钙超载,同时亦可改善心功能     

含丹参磷酸钙骨水泥的制备和表征

目的探索含中药的磷酸钙骨水泥(CPC)的制备方法,并表征其理化性能.方法采用两种方法制备含中药的CPC,第一种通过在液相中加入中药香丹注射液(主要成分为丹参),第二种用喷雾干燥的方法制备含中药丹参的磷酸氢钙粉末作为CPC的主要成分之一,通过固相加入中药.采用万能材料试验机测试其力学性能,采用微量热分析仪、红外光谱仪、X射线衍射仪表征含丹参CPC的基本理化性能.结果通过喷雾干燥的方法加入丹参不仅比通过液相加入更有效,而且加入丹参后,其理化性能变化甚微.结论可用喷雾干燥法制备含中药的磷酸氢钙粉末,作为起始原料制备含丹参的CPC.     

Human immunodeficiency virus type 1 Tat protein induces an intracellular calcium increase in human monocytes that requires DHP receptors: involvement in TNF-alpha production

HIV-1 Tat protein, acting at the cell membrane, stimulates the production by human monocytes of TNF-α, a cytokine implicated in both HIV-1 replication and pathogenesis. Here, we analyze, in primary human monocytes, the mechanisms involved in Tat-stimulated calcium mobilization and its relationship with TNF-α production. We show that the Tat protein induces a calcium signal by mobilizing calcium from extracellular stores. This calcium signal is totally blocked when cells are stimulated in the presence of DHP receptor inhibitors such as nimodipine or calcicludine, thus suggesting the implication of this L-type calcium channel. By using RT-PCR amplification, Western blot with antibodies directed against the α1D subunit, binding assays with specific agonists or antagonists, and inhibition with specific antisense oligonucleotides, we show that DHP receptors are expressed and functional in primary human monocytes. Interestingly, we demonstrate that Tat-induced calcium mobilization is tightly linked to TNF-α production, thus indicating that Tat-induced mobilization and TNF-α production are entirely mediated by DHP receptors, as shown by their total inhibition by nimodipine, calcicludine, or anti-α1D antisense oligonucleotides.