维生素D3和华法令诱导的大鼠动脉钙化模型特点

目的：探讨维生素D3联合华法令对大鼠动脉钙化的作用，为心血管疾病的康复预防措施介入提供基础研究数据。方法：实验选用12只4周龄雄性SD大鼠，随机分为钙化组和正常组，每组6只。钙化组给予皮下注射维生素D3 3&;#215;10^5U／(kg&;#183;d)，持续3d，同时华法令15mg／(100g&;#183;12h)，持续4d，制备大鼠动脉钙化模型。取腹主动脉制成石蜡切片von Kossa染色观察动脉钙化情况，同时取胸主动脉按RT-PCR方法检测骨保护素的表达，另取右侧胫骨测量骨密度。结果：钙化组大鼠主动脉von Kossa染色见中膜有成片或局灶黑色深染区域，为主动脉的钙化部位。正常组主动脉壁骨保护素mRNA相对含量[(45．6&;#177;0．6)％]明显高于钙化组[(24．6&;#177;0．4)％](P&;lt;0．05)。正常组大鼠胫骨骨密度[(0．108&;#177;0．032)g／cm^2]高于钙化组[(0．082&;#177;0．038)g／cm^2]，但差异无显著性意义(P&;gt;0．05)。结论：华法令和维生素D3能诱导大鼠主动脉中膜钙化，钙化的主动脉局部骨保护素的表达水平降低。     

腹膜透析患者维生素D水平与血管钙化相关性研究

目的 了解持续不卧床腹膜透析(continuous ambulatory peritoneal dialysis,CAPD)患者血1,25(OH)2D3水平及血管钙化情况,探讨CAPD患者血管钙化的相关因素及血1,25(OH)2D3水平测定在腹主动脉钙化(abdominal aortic calcification, AAC)中的作用及意义。方法 选取河北医科大学第二医院行CAPD 3个月以上患者84例,收集其临床资料,侧位X线平片评估AAC情况,计算腹主动脉钙化积分(abdominal aortic calcification score,AACs)。酶联免疫吸附测定检测血清1,25(OH)2D3浓度。相关分析法分析1,25(OH)2D3与AACs关系,Logistic回归法和多元回归法进行血管钙化相关危险因素分析,受试者工作曲线（ROC）评价1,25(OH)2D3预测AAC的准确性。结果 84例CAPD患者中,AAC患者34例(42.5%),CAPD患者血清1,25(OH)2D3水平较低,与AAC呈负相关,口服骨化三醇可提高血清1,25(OH)2D3浓度。Logistic回归分析显示高龄、罹患糖尿病、服用骨化三醇、高胆固醇、高磷、高血尿酸、低1,25(OH)2D3为血管钙化发生的危险因素(P<0.05),多元回归分析结果显示去除混杂因素后,年龄、血磷、1, 25(OH)2D3是AAC进展的独立影响因素(P<0.05)。1,25(OH)2D3 ROC曲线下面积(AUC)为0.652（95%CI=0.442~0.696,P<0.05）, 提示1,25(OH)2D3预测AAC有一定准确性,取1,25(OH)2D3浓度为250.43 pg/ml作为截点时,其预测AAC的敏感性为55.9%,特异性为66%,约登指数为0.219。结论 CAPD患者血清1,25(OH)2D3水平与AAC程度呈负相关,低血清1,25(OH)2D3水平是AAC的独立危险因素之一。口服骨化三醇可改善CAPD患者1,25(OH)2D3水平,但口服骨化三醇可增加血管钙化的风险,监测1,25(OH)2D3水平可预测血管钙化的风险。     

冠状动脉旁路移植伴升主动脉钙化斑块21例分析

冠状动脉旁路移植伴有升主动脉严重钙化斑块,术前大多数常规检查难以发现,只有通过术中扪摸发现.对主动脉插管、上阻断钳,做近端吻合有很大的困难和风险,易导致钙化组织脱落,引起脑部并发症.对我院2000-06～2005-11收治的升主动脉严重钙化斑块21例分析如下.     

8个家族性特发性基底节钙化家系的临床特点及遗传规律研究

【目的】探讨8个家族性特发性基底节钙化(FIBGC)家系的临床特点及遗传规律。【方法】收集8个 FIBGC 家系,根据临床表现分为运动受损组和精神症状组,绘制家系图,分析先证者及家系其他患者的发病年龄、临床表现、基底节区钙化的体积,总结遗传规律。【结果】8个家系均呈常染色体显性遗传,先证者的性别比：男/女=4/4;患者的性别比：男/女=18/17,两组先证者人数构成比：运动受损/精神症状=4/4,运动受损组与精神症状组性别比(男/女)无显著性差异[(3/1)vs (1/3),P >0.05]。两组先证者的发病年龄[(43.00±3.16)岁 vs(29.50±6.95)岁]和基底节区钙化的体积[(1.526±0.679)cm3 vs(0.233±0.114)cm3]比较差异具有统计学意义(P <0.05)。临床特点：患者均表现为一个系统损害的症状,运动系统受损或者精神症状。以运动受损的4个家系其他成员发病的症状也以运动受损为特点,精神症状为主的4个家系仅5人有精神症状,其他成员均没有临床症状。【结论】FIBGC 临床表现具有明显的异质性,以运动受损的患者其病情严重程度与基底节区钙化病灶的大小相关,且发病年龄较晚,家系成员临床症状具有遗传性;以精神症状为主的患者其基底节区钙化病灶小,发病年龄早,家系成员临床症状遗传性不明显。     

16层螺旋CT冠状动脉钙化积分的临床价值

冠心病是一种常见病、多发病,常导致严重后果.随着发病率的不断提高,对无症状冠心病的检出提出了更高的要求.冠状动脉钙化（CAC）与冠状动脉粥样硬化之间关系密切.但临床对CAC进行准确定量评价较为困难.我院自16层螺旋CT投入使用以来,结合心电门控技术进行冠状动脉钙化积分分析,进而评估冠心病发生的风险,现报告如下.     

维生素D3对糖尿病大鼠肾脏的保护作用

目的 探讨维生素 D3对糖尿病大鼠肾脏的保护作用及其机制. 方法实验选用 3月龄雌性 SD大鼠(清洁级) 30只.按随机数字表法分为 3组,分别为正常对照组,糖尿病模型组,维生素 D3治疗组,每组 10只.检测各组第 4,8周时血糖、糖化血红蛋白、血肌酐、尿素氮、尿白蛋白、血胆固醇、三酰甘油,转化生长因子-β 1 (transforming growth factor-beta 1,TGF β 1)水平等指标的变化,用 RT-PCR方法检测各组大鼠肾皮质 TGF β 1表达水平的变化,免疫组化法检测纤维连接蛋白 (fibronectin,FN)和层黏连蛋白 (liminin, LN)表达水平的变化. 结果实验 4周时维生素 D3治疗组尿白蛋白排泄率 [(10.28± 1.09)μ g/24 h]较糖尿病模型组 [(12.62± 0.51)μ g/24 h]减少 (t=3.987,P< 0.05),8周时也明显减少( t=4.475, P< 0.01).实验 8周时维生素 D3治疗组血 TGF β 1水平较糖尿病模型组明显下降( t=2.704, P< 0.05).实验 4, 8周时维生素 D3治疗组肾皮质 TGF β 1表达水平较糖尿病模型组明显下降 (t=7.697,P< 0.01;t=3.068,P< 0.05).免疫组化显示糖尿病大鼠肾小球 FN和 LN沉积增多,维生素 D3治疗组 FN和 LN表达低于糖尿病模型组( t=- 3.228,- 1.432, P< 0.01). 结论 维生素 D3对于糖尿病肾脏病变具有部分保护作用,其机制可能为通过下调糖尿病大鼠 TGF β 1的表达,抑制血中 TGF β 1水平,从而减少细胞外基质的沉积.     

维生素D致肥胖大鼠模型的实验研究

目的：提供一种简易、经济、快速、便捷地诱发肥胖模型的方法。方法：将雄性SD大鼠30只随机分为实验组和对照组，每组15只。实验组一次性腹腔注射维生素D300U／g，对照组同时注射等量生理盐水。存活30d后测Lee’s指数、脂肪系数、600倍光镜每视野脂肪细胞个数及血清瘦素水平。结果：实验组Lee’s指数及脂肪系数(分别为313．7&;#177;6．9，0．26&;#177;0．05)明显高于对照组(分别为302．6&;#177;4．2，0．13&;#177;0．03)(t=5.352，9．455．P&;lt;0．05)；实验组每视野脂肪细胞个数、血清瘦素水平[实验组：(31．2&;#177;17.6)μg／L．对照组：(7．5&;#177;6．3)μg／L]明显低于对照组(t=5.481，4．912，P&;lt;0．05)。结论：一次性腹腔大剂量注射维生素D能方便快捷地诱发肥胖。     

骨髓间质干细胞移植对骨桥蛋白表达水平和血管钙化发生的干预作用

目的:研究骨髓间质干细胞对于大鼠血管尤其是大血管钙化的修复作用。方法:实验于2004-01-15/30在武警部队心血管疾病研究所完成。选用8周龄健康Wistar鼠32只。采用尼古丁与维生素D3制作大鼠血管钙化模型,造模后随机将模型组动物分为骨髓间质干细胞干预组(n=12)及单纯造模组(n=12);空白对照组(n=8)采用生理盐水灌胃并注射。14d后处死动物检测不同组别动物组织钙含量、组织中钙容积分数及参与动脉壁钙化的骨桥蛋白的表达水平。结果:最终进入结果分析大鼠32只。①单纯造模组和骨髓间质干细胞干预组大鼠主动脉组织钙含量明显高于空白对照组犤(29.90±1.85),(13.80±1.28),(2.61±0.45)mg/g,F=644.996,P<0.01犦。②骨髓间质细胞干预组大鼠动脉钙含量明显低于单纯造模组(q=9.361,P<0.01)。组织中钙容积分数明显低于单纯造模组。③单纯造模组动脉壁中可见大量黑色大颗粒物质的沉积,而骨髓间质干细胞干预组的动物切片染色后在动脉内膜部分可见散在的黑色颗粒状物质,并没有聚集成片。④空白对照组骨桥蛋白基本不表达,单纯造模组动物主动脉中骨桥蛋白表达明显增加,骨髓间质干细胞干预组骨桥蛋白虽有表达,但水平明显低于单纯造模组,介于对照组与单纯造模组之间,采用光密度扫描分析同样证实此结果。结论:骨髓间质干细胞移植治疗可以改变血管中钙含量,降低大鼠血管壁中骨桥蛋白表达水平,减少钙在血管组织局部的沉积,从而有效地防止血管钙化的发生。     

维生素D致肥胖大鼠模型的实验研究

目的提供一种简易、经济、快速、便捷地诱发肥胖模型的方法. 方法将雄性 SD大鼠 30只随机分为实验组和对照组,每组 15只.实验组一次性腹腔注射维生素 D300 U/g,对照组同时注射等量生理盐水.存活 30 d后测 Lee's指数、脂肪系数、 600倍光镜每视野脂肪细胞个数及血清瘦素水平. 结果实验组 Lee's指数及脂肪系数 (分别为 313.7± 6.9, 0.26± 0.05)明显高于对照组 (分别为 302.6± 4.2, 0.13± 0.03)(t=5.352,9.455,P< 0.05);实验组每视野脂肪细胞个数、血清瘦素水平 [实验组(31.2± 17.6)μ g/L, 对照组 (7.5± 6.3) μ g/L〗明显低于对照组 (t=5.481,4.912,P< 0.05). 结论一次性腹腔大剂量注射维生素 D能方便快捷地诱发肥胖.     

Long-term warfarin treatment may induce arterial calcification in humans: case report

PURPOSE: To report a case of arterial calcification in a person who has had long-term treatment with warfarin. Although the anticoagulant has been shown to induce arterial calcification in laboratory animals, there have been no previous reports implicating warfarin as a clinical factor. CLINICAL FEATURES: On routine annual examination, the coronary arteries of a healthy man with no symptoms who has had long-term warfarin treatment were found to be highly calcified. CONCLUSION: It would be prudent to further evaluate experimentally the relationship of warfarin and arterial calcification. We suggest that physicians prescribing long-term warfarin treatment consider arterial calcification as one of its potential consequences.     

Role of vitamin D in arterial hypertension

Vitamin D deficiency is highly prevalent and may contribute to arterial hypertension. The antihypertensive effects of vitamin D include suppression of renin and parathyroid hormone levels and renoprotective, anti-inflammatory and vasculoprotective properties. Low 25-hydroxyvitamin D levels, which are used to classify the vitamin D status, are an independent risk factor for incident arterial hypertension. Meta-analyses of randomized controlled trials showed that vitamin D supplementation reduces systolic blood pressure by 2–6 mmHg. However, further studies are needed before drawing a final conclusion on the effect of vitamin D therapy on blood pressure and cardiovascular risk. In our current clinical practice we should take into account the high prevalence of vitamin D deficiency, the easy, cheap and safe way by which it can be supplemented and the promising clinical data suggesting that vitamin D might be useful for the treatment of arterial hypertension as well as other chronic diseases. Therefore, we recommend that testing for and treating vitamin D deficiency in patients with arterial hypertension should be seriously considered.     

Role of vitamin D in arterial hypertension

Vitamin D deficiency is highly prevalent and may contribute to arterial hypertension. The antihypertensive effects of vitamin D include suppression of renin and parathyroid hormone levels and renoprotective, anti-inflammatory and vasculoprotective properties. Low 25-hydroxyvitamin D levels, which are used to classify the vitamin D status, are an independent risk factor for incident arterial hypertension. Meta-analyses of randomized controlled trials showed that vitamin D supplementation reduces systolic blood pressure by 2-6 mmHg. However, further studies are needed before drawing a final conclusion on the effect of vitamin D therapy on blood pressure and cardiovascular risk. In our current clinical practice we should take into account the high prevalence of vitamin D deficiency, the easy, cheap and safe way by which it can be supplemented and the promising clinical data suggesting that vitamin D might be useful for the treatment of arterial hypertension as well as other chronic diseases. Therefore, we recommend that testing for and treating vitamin D deficiency in patients with arterial hypertension should be seriously considered.     

6-羟基多巴胺制备帕金森病大鼠模型的神经行为学特点

目的:采用在大鼠脑右侧黑质注射6-羟基多巴胺制备帕金森病模型,观察帕金森病模型大鼠神经行为学的特点。方法:实验于2001-03/12在上海中医药大学病理学实验室完成。将62只Wistar大鼠随机分为3组。模型组:采用6-羟基多巴胺(溶于含0.2g/L抗坏血酸的生理盐水中,浓度为2g/L,以1.0mm/min速度缓慢进针,3μL/孔,注射速度为1μL/min,注射完毕后留针5min,然后以1.0mm/min速度缓慢退针)。注射于大鼠脑右侧黑质造成偏侧帕金森病模型。假手术组:注射含0.2g/L抗坏血酸的等量生理盐水,其余条件与模型组相同。正常对照组:不进行任何处理。在模型制备后第10天,以腹腔注射阿朴吗啡0.5mg/kg诱发大鼠向一侧旋转,记录开始旋转至30min内的旋转圈数,以旋转圈数平均每分钟超过7次者为合格的帕金森病模型。并观察各组大鼠在第45天的旋转行为。结果:62只大鼠中有23只大鼠造模不成功,39只大鼠进入结果分析。①正常对照组、假手术组无旋转行为。模型组在腹腔注射阿朴吗啡后0.5～4min,均开始出现旋转行为,即以左侧后肢为支点原地旋转,头尾相接,身体成环状,同时还伴有觅食、嗅探动作。②42只模型组大鼠中,造模成功19只,成功率为45%(19/42)。向左旋转的大鼠显著多于向右旋转及向左一圈,右一圈旋转的大鼠[14只,4只,1只,(P<0.05)]。③模型组在第45天的旋转圈数与第10天时接近[(526.10±173.96),(538.52±187.88)圈/h,(t=1.448,P>0.05)]。结论:①模型大鼠具有典型的神经行为学特点,主要表现为以健侧后肢为支点原地旋转。②该模型不能自行恢复,是研究帕金森病的稳定、可靠模型。     

6-羟基多巴胺制备帕金森病大鼠模型的神经行为学特点

目的：采用在大鼠脑右侧黑质注射6-羟基多巴胺制备帕金森病模型，观察帕金森病模型大鼠神经行为学的特点。方法：实验于2001—03／12在上海中医药大学病理学实验室完成。将62只Wistar大鼠随机分为3组。模型组：采用6-羟基多巴胺（溶于含0．2g／L抗坏血酸的生理盐水中，浓度为2叽。以1．0mm／min速度缓慢进针。3μL／孔，注射速度为1μL／min。注射完毕后留针5min，然后以1．0mm／min速度缓慢退针）。注射于大鼠脑右侧黑质造成偏侧帕金森病模型。假手术组：注射含0．2g／L抗坏血酸的等量生理盐水，其余条件与模型组相同。正常对照组：不进行任何处理。在模型制备后第10天，以腹腔注射阿朴吗啡0．5mg/kg诱发大鼠向一侧旋转，记录开始旋转至30min内的旋转圈数。以旋转圈数平均每分钟超过7次者为合格的帕金森病模型。并观察各组大鼠在第45天的旋转行为。结果：62只大鼠中有23只大鼠造模不成功，39只大鼠进入结果分析。①正常对照组、假手术组无旋转行为。模型组在腹腔注射阿朴吗啡后0．5-4min，均开始出现旋转行为，即以左侧后肢为支点原地旋转，头尾相接，身体成环状，同时还伴有觅食、嗅探动作。②42只模型组大鼠中，造模成功19只，成功率为45％（19／42）。向左旋转的大鼠显著多于向右旋转及向左一圈，右一圈旋转的大鼠[14只，4只，1只，（P〈0．05）]。③模型组在第45天的旋转圈数与第10天时接近[（526．10&;#177;173．96），（538．52&;#177;187．88）圈／h。（t=1．448，P〉0．05）1。结论：①模型大鼠具有典型的神经行为学特点。主要表现为以健侧后肢为支点原地旋转。②该模型不能自行恢复，是研究帕金森病的稳定、可靠模型。     

The impact of vitamin K-dependent factor depletion by warfarin on platelet-rich thrombosis after deep arterial injury.

Although the central role of thrombin in arterial thrombosis is well established, the efficacy of vitamin K-dependent factor depletion by warfarin at preventing this process has not been established. To assess the efficacy of warfarin in the prevention of arterial thrombosis, two intensities of anticoagulation were compared in a well-characterized porcine model of carotid angioplasty. For 10 days prior to angioplasty, pigs received either high-dose warfarin (n = 9), low-dose warfarin plus aspirin (n = 9), or control tablets (n = 10). Injured arteries were assessed for (111)In-platelet ( x 10(6) cm(-2)) and (125)I-fibrin(ogen) (molecules x 10(12) cm(-2)) deposition and the incidence of macroscopic thrombus. Platelet (30 +/- 7 vs. 332 +/- 137; P = 0.001) and fibrinogen (156 +/- 17 vs. 365 +/- 90; P < 0.05) deposition were significantly reduced in animals receiving high-intensity warfarin whereas low-intensity warfarin/ASA (520 +/- 240 and 1193 +/- 638) was similar to control (P =NS). At the time of angioplasty, the PT-INR and vitamin K-dependent factors varied over a broad range. The greatest reduction of platelet and fibrinogen deposition occurred as the PT-INR increased from 1.0 to 2.2. Increasing the PT-INR beyond 3.0 resulted in little, if any, incremental reduction of either platelet or fibrinogen deposition. Macroscopic thrombus was abolished at PT-INR > 2.2. Despite a broad range of vitamin K factor activities, no single factor was predictive of either platelet or fibrinogen deposition. Warfarin at PT-INR > 2.2 effectively eliminates thrombosis following deep arterial injury. Arterial thrombosis correlates poorly with any single vitamin K-dependent factor but rather appears to be a function of the entire extrinsic coagulation pathway as measured by the PT-INR.