骨关节炎动物模型的生化及磁共振成像研究

目的动态观察豚鼠关节软骨降解的生化及形态学改变，探讨骨关节炎早期病变机制：研究磁共振成像（MRI）检测早期软骨退变的可能性及其表现。方法选用Harfley雌性豚鼠30只，分为出生后1、3、6个月龄，每组各10只。观察豚鼠膝关节软骨降解情况，测定其血清蛋白多糖和雌二醇水平，取胫骨平台软骨测定羟脯氨酸、糖醛酸含量及含水率。取关节软骨组织作蛋白多糖含量测定和组织病理学检查，同时行双侧膝关节矢状面T1WI、PDW和T2WI成像检查。结果3个月组关节软骨即有降解。豚鼠的雌二醇水平和软骨含水率随年龄的增长而升高，而血清蛋白多糖和软骨糖醛酸含量随年龄的增长而下降，各组间差异有统计学意义（P〈0．05）。软骨羟脯氨酸含量各时间段差异无统计学意义，3个月组关节软骨明显变薄，磁共振（MR）信号强度明显降低。6个月组更加明显，与出生后1个月相比，两者差异均有统计学意义（P〈0．05），关节软骨明湿变薄，MR信号强度明显降低；与对照1个月组比较，两者差异均有统计学意义（P〈0．05）。结论原发性骨关节炎血清及软骨生化指标随年龄增高改变明显。雌激素代谢盯能与原发性骨关节炎的发病机制有关。关节软骨的MR信号强度与蛋白多糖含量具有相关性．蛋白多糖的降解在MRI上表现为软骨厚度的变薄和MRI信号强度的降低。这表明通过MRI检查，有可能发现早期的软骨退变。     

高脱乙酰度羧甲基壳聚糖对兔膝骨关节炎软骨诱导型一氧化氮合酶表达的影响

目的观察高脱乙酰度羧甲基壳聚糖(HD-CMC)经关节腔注射后对兔膝骨关节炎(OA)软骨诱导型一氧化氮合酶(iNOS)的mRNA和蛋白表达的影响,探讨其用于OA防治的机制及可能性。方法36只日本大耳白兔,行右侧膝关节前交叉韧带切断术(ACLT),术后随机分为2组,实验组于术后当天开始关节腔内注射2%HD-CMC 0．15mg/kg,每2周给药1次,对照组同一时间点关节腔内注射0．9%生理盐水0．15mg/kg。实验组与对照组于第6周分别随机处死大白兔各9只,剩余大白兔于第12周处死,对比两组大白兔股骨髁关节软骨的大体改变,用反转录聚合酶链反应(RT-PCR)及免疫组织化学的方法检测iNOS在软骨中的mRNA和蛋白的表达。结果实验组退变软骨的大体评分轻于对照组,NOS的mRNA和蛋白表达水平均低于对照组。结论HD-CMC能够降低OA退变软骨iNOS的表达,并延缓软骨的退行性变,对OA退变软骨具有修复保护作用。     

盘状结构域受体2与软骨破坏程度的相关研究

目的 观察盘状结构域受体(DDR)2和基质金属蛋白酶(MMP)-13在膝骨关节炎(OA)大鼠不同时期软骨及滑膜中的表达,探讨DDR2与关节软骨破坏之间的关系.方法 采用改良膝关节腔内注射木瓜蛋白酶法制作OA大鼠模型,从蛋白水平检测造模后不同病理阶段关节软骨及滑膜中DDR2和MMP-13的表达规律和分布特点.结果 DDR2在各模型组关节软骨及滑膜中的表达较健康组增高(P＜0.01),并且各组中软骨表达高于相应滑膜,MMP-13表达呈现与DDR2相同的特点,二者相关系数r=0.93(P＜0.01).结论 初步证明"DDR2-MMP-13-软骨破坏"途径在OA病理过程中起重要作用.软骨和滑膜DDR2的表达升高共同促进软骨退变.     

壳聚糖膝关节腔内注射疗法对兔骨关节炎关节软骨的影响

目的观察关节内注射羧甲基壳聚糖(CMCTS)对兔骨关节炎(OA)关节软骨退变及软骨基质金属蛋白酶(MMP)-1,-3mRNA表达的影响。方法24只大耳白兔行单侧膝关节前交叉韧带切断术,术后5周将动物随机分为3组,A组关节内注射2%CMCTS0.3ml,每2周1次;B组关节内注射1%透明质酸钠(HA)0.3ml,每周1次;C组关节内不注射药物。术后11周处死动物,观察各组股骨内髁关节软骨的大体变化,采用反转录-聚合酶链反应(RT-PCR)方法检测股骨内髁退变软骨中MMP-1和MMP-3的mRNA表达。结果CMCTS和HA注射组软骨退变程度较不用药组明显减轻,CMCTS注射组软骨MMP-1、MMP-3的mRNA表达明显低于HA注射组和不用药组。HA注射组软骨MMP-1和MMP-3的mRNA表达与不用药组比较,差异没有显著性意义。结论CMCTS能够明显抑制OA软骨MMP-1和MMP-3的mRNA表达,明显减轻软骨退变的程度,CMCTS对早期OA软骨有修复保护作用。     

褪黑激素对大鼠膝骨关节炎的治疗作用

目的 通过观察褪黑激素（MLT）对大鼠膝骨关节炎（OA）软骨的影响，探讨OA的发病机制及MLT不同给药方式对OA的治疗作用。方法 40只Wistar大鼠随机分为四组：正常对照组（A组），模型对照组（B组），MLT膝关节腔注射组（C组），MLT腹腔注射组（D组）。4％木瓜蛋白酶在1、4、7d于双侧膝关节腔各注射0．15ml建立OA模型，第8天开始D组腹腔注射MLT1次／d，C组关节腔每3d注射MLT1次，给药7周后处死，切取胫骨平台关节软骨大体观察，HE及甲苯胺蓝染色，Mankin评分，检测血清、关节液及滑膜中超氧化物歧化酶（SOD）、丙二醛（MDA）、一氧化氮（NO）。结果 模型组关节软骨磨损，退变，软骨性骨赘形成。光镜下关节软骨表面磨损不规则，裂隙深及钙化层，部分软骨缺失，软骨细胞坏死，潮线紊乱，Mankin评分高。与B组比较，C组关节软骨形态学上明显改善，血清及关节液中SOD明显升高（P〈0．01），NO、MDA均明显降低（P〈0．01），而D组则未见明显改善。结论 MLT能有效防治实验性OA；关节腔注射MLT治疗0A的疗效明显优于腹腔注射。     

羧甲基化几丁质降低兔实验性骨关节炎软骨基质金属蛋白酶-1表达的实验研究

目的 观察羧甲基化几丁质(CMC)经关节内注射后对兔前交叉韧带切断(ACLT)骨关节炎模型中软骨退变及软骨基质金属蛋白酶-1(MMP-1)表达及分布的影响。方法 20只大白兔行单侧ACLT，随机选取10只作实验组，于术后第1、3、5周分别给予0.3ml 2% CMC关节内注射，另10只于同一时间点给予0．3m1生理盐水关节内注射作对照组。术后第6周处死大白兔，对比两组大白兔股骨髁关节软骨的大体改变和光镜下的病理改变，并用反转录-聚合酶链反应（RT-PCR)及免疫组织化学的方法检测MMP—1在软骨中的mRNA和蛋白表达。结果 实验组软骨退变的大体评分和光镜下Mankin‘s评分都显著低于对照组，RT—PCR亦显示MMP-1在实验组中的表达明显低于其在对照组中的表达。免疫组织化学显示MMP-1主要表达于软骨表层及中上层，实验组MMP-1表达量亦明显低于对照组．结论 CMC能明显降低骨关节炎(OA)软骨中MMP-1的mRNA和生白表达水平，并明显降低软骨退变的程度，有可能成为防治OA的良好药物。     

透明质酸钠对兔骨关节炎软骨诱导型NO合酶基因表达的影响

目的观察透明质酸钠(Na—HA)关节腔注射对骨关节炎(OA)模型关节软骨中诱导型NO合酶(iNOS) mRNA表达水平的影响。方法16只大耳白兔行单侧前交叉韧带切断术，术后5周将动物随机分为实验组和对照组，实验组关节腔注射1％Na—HA 0.3ml，每周1次，连续5周，对照组则注射等量生理盐水。术后10周处死动物，观察两组股骨内髁关节软骨的大体形态学和组织学病理改变，采用反转录一聚合酶链反应(RT—PCR)方法检测软骨iNOS mRNA的表达。结果实验组软骨退变程度较对照组明显减轻，实验组软骨中iNOS mRNA的表达水平与对照组比较差异无统计学意义。结论Na—HA能有效地减轻早期OA关节软骨的退变程度，Na—HA对早期OA软骨中的iNOS的表达没有下调作用。     

内质网跨膜蛋白肌醇需求酶1α介导的凋亡通路在兔骨关节炎发病中的作用及机制

目的探讨内质网跨膜蛋白肌醇需求酶(IRE)1α介导的凋亡通路在骨关节炎(OA)发病中的作用及机制。方法新西兰兔膝关节注射木瓜蛋白酶模拟OA模型,HE染色检测OA关节软骨以及关节滑膜的形态,ELISA法检测OA关节滑膜中炎性因子白细胞介素(IL)-6的含量。检测闭合性松解术关节软骨的组织形态以及IL-6的含量。Western印迹检测IRE1α介导的凋亡通路在OA滑膜中的表达水平。结果 HE染色结果显示木瓜蛋白酶诱导的OA模型中,关节软骨细胞发生明显坏死,纤维组织变性、机化以及纤维蛋白坏死物沉积,ELISA结果显示关节滑膜中的IL-6水平明显升高,闭合性松解术后的OA关节软骨细胞凋亡减少,且关节滑膜中IL-6水平也明显降低。蛋白水平显示OA膝关节滑膜中IRE1α的磷酸化水平以及Caspase3的表达水平明显升高,介导关节软骨细胞的凋亡,而闭合性松解术后Caspase3的表达水平降低。结论闭合性松解术可缓解OA的症状,抑制IRE1α-Caspase3信号通路介导的凋亡作用。     

兔骨关节炎关节软骨含水率随时间变化的实验研究

骨关节炎 (ｏｓｔｅｏａｒｔｈｒｉｔｉｓ,ＯＡ)的主要病理改变在关节软骨 ,关节软骨中水占湿重的 80 % ,在关节软骨的生化组成中所占比例最大 ,水与蛋白多糖及胶原相结合共同提供了软骨细胞生物学功能的内环境。在ＯＡ时 ,关节软骨内的各个生化组成部分都在发生“退变” ,本实验观察了兔骨关节炎不同时间点内关节软骨的含水率 ,旨在研究伴随软骨退变程度的加重 ,关节软骨含水率的动态变化情况。1　材料与方法1 1　实验动物48只新西兰大白兔 ,6个月龄 ,雌性 ,体重 (2 5 0± 0 10 )ｋｇ ,由上海中医药大学实验动物中心提供。随机分为模型组…     

实验性肝细胞癌铁铜含量与MR成象的关系

目的初步阐明在MRI常规SE序列,铁、铜元素对肝细胞癌TIWI信号的影响.方法20g/LDEN灌喂Wistar大鼠(n=80),诱癌成功后行常规SE序列T1WI,T2WI扫描,对照组(n=20)不灌喂DEN.扫描后处死动物取肝组织与肝癌组织作HE、普鲁士蓝染色,并测定组织内水、铁、铜含量.结果肝癌与癌周组织含水量无显著差异,肝癌内铁含量低于癌周肝组织,肝癌内的铜含量高于癌周肝组织,在呈低信号的肝癌组织内含铁血黄素明显高于其他信号强度类型,在呈高信号的肝癌组织内明显高于其他信号强度类型的肝癌组织.结论水的含量不是影响肝癌MR表现的主要因素,肝癌内含铁血黄素在SE T1WI呈低信号起作用,肝癌内铜的蓄积对SET1WI呈高信号起作用.     

Cartilage signal intensity on T1-weighted MRI: association with risk factors and measures of knee osteoarthritis

This study aims to assess mean signal intensity of cartilage on T1-weighted magnetic resonance imaging (MRI) images, and then examine whether mean signal intensity is associated with risk factors and measures of osteoarthritis in younger and older adults. A total of 50 younger adult subjects (mean age 41, range 29–57; 64 % female; baseline only) and 168 older adult subjects (mean age 63, range 52–78; 46 % female; baseline and 2.9 year followup) were randomly selected from the community. T1-weighted fat-supressed gradient recall echo MRI scans of right knees were performed. Image segmentation was performed semi-automatically, and measures of mean signal intensity and cartilage thickness for regions of cartilage were obtained. Urinary levels of C-terminal crosslinking telopeptide of type II collagen (U-CTX-II) were measured in younger adults. Cartilage defects were scored using a 5-point scale in both groups. In multivariable analyses, higher cartilage defects and BMI were significantly associated with lower same-region mean signal intensity in younger and older adults. CTX-II was negatively and significantly associated with mean signal intensity of cartilage in the lateral femoral and patellar sites. Joint space narrowing and osteophytes analysed in older adults were significantly associated with reduced mean signal intensity at various sites. Over 2.9 years, lower mean signal intensity at femoral and patellar sites and in whole knee was associated with decreases in cartilage thickness. Reduced mean signal intensity of cartilage on T1-weighted gradient recall echo MRI is associated with osteoarthritis risk factors and predicts cartilage loss suggesting low cartilage signal intensity may reflect early osteoarthritic changes.     

磁共振成像在类风湿关节炎患者膝关节病变研究中的意义

目的　初步探讨磁共振成像 (MRI)技术在类风湿关节炎 (RA)患者膝关节病变临床诊断中的应用价值。方法　对 2 0例RA患者的 34个膝关节进行多种序列成像并分析其MRI表现。结果　MRI可清晰显示RA膝关节的滑膜增生及血管翳形成、关节软骨破坏、骨质受侵、关节囊积液、半月板及韧带异常、窝囊肿形成以及皮下结节等改变 ,并能通过血管翳的信号和强化程度判断疾病是否处于活动期。结论　与X线相比 ,MRI对RA的骨质侵蚀破坏更为敏感 (P <0 0 1)。MRI能直接显示RA患者膝关节不同时期的各种改变 ,有助于疾病的早期诊断和临床分期     

颅内出血的磁共振成像

MRI的常规序列T1加权成像、T2加权成像和液体衰减反转恢复(FLAIR)序列均可敏感地检出亚急性期和慢性期颅内出血;梯度回波成像可检出各期颅内出血,但血肿信号强度与血肿存在的时间无相关性。弥散加权成像和表观弥散系数能提供更多有关血肿中心区、周围区和梗死后出血的信息。     

New imaging techniques in the evaluation of joint cartilage

Magnetic resonance (MR) imaging provides an excellent spatial resolution to visualize cartilage and define its main properties. Both 1.5 and especially 3 Tesla equipments have become very efficient in showing the whole articular cartilage and classifying the degenerative damage by analyzing morphological, structural and physical properties. MR evaluation of articular cartilage is of great clinical importance due to the prevalence of degenerative lesions and the development of new drugs and surgery-based treatments. In this work we explain the advances in the MR quantitation of the articular cartilage properties, particularly focusing on T2 and T1 relaxation times, the distribution of first-pass contrast agent (pharmacokinetic study) and late enhancement percentage. By using specific sequences and adequate measuring techniques, MR allows the evaluation of important parameters such as cartilage surface, thickness and volume; signal intensity and the physical properties related to collagen integrity and edema; cartilage perfusion and endothelial permeability related to neovascularization; and the presence of late enhancement areas, related to proteoglycan concentrations. This information will aid early diagnosis, establishment of the degree of degeneration, assessment of prognosis, definition of therapeutic options and evaluation of treatment effectiveness. The study of the cartilage structural and functional alterations by MR imaging is an excellent biomarker of tissue degeneration.     

Magnetic resonance imaging in osteoarthritis of the knee: correlation with radiographic and scintigraphic findings.

Twelve knees with a range of severity of knee osteoarthritis were assessed by magnetic resonance imaging (MRI) and technetium-99m labelled hydroxymethylene diphosphonate scintigraphy. Five magnetic resonance pulse sequences were evaluated. Proton density (TR = 1000, TE = 26 ms) and STIR (TR = 1500, TI = 100, TE = 30 ms) were chosen for further use. Abnormalities shown by MRI included joint effusions, meniscal disruption, hyaline cartilage thinning, subchondral signal changes, pseudocysts, and heterogeneity of signal from osteophytes. Certain MRI and scintigraphic appearances correlated: (a) 'hyperintense osteophytosis' and ipsilateral 'tramline' scintigraphic uptake, suggesting increased fat content in 'active' osteophytes; (b) subchondral signal change and 'extended' pattern, possibly reflecting inflammation, synovial leak, or fibrovascular repair; (c) patellofemoral joint signal changes and patellar isotope uptake.     

Diagnostic significance of gadolinium-DTPA (diethylenetriamine penta-acetic acid) enhanced magnetic resonance imaging in thrombolytic treatment for acute myocardial infarction: its potential in assessing reperfusion

The diagnostic value of gadolinium-DTPA (diethylenetriamine penta-acetic acid) enhanced magnetic resonance imaging in patients treated by thrombolysis for acute myocardial infarction was assessed in 27 consecutive patients who had a first acute myocardial infarction (14 anterior, 13 inferior) and who underwent thrombolytic treatment and coronary arteriography within 4 hours of the onset of symptoms. Magnetic resonance imaging was performed 93 hours (range 15-241) after the onset of symptoms. A Philips Gyroscan (0.5 T) was used, and spin echo measurements (echo time 30 ms) were made before and 20 minutes after intravenous injection of 0.1 mmol/kg gadolinium-DTPA. In all patients contrast enhancement of the infarcted areas was seen after Gd-DTPA. The signal intensities of the infarcted and normal values were used to calculate the intensity ratios. Mean (SD) intensity ratios after Gd-DTPA were significantly increased (1.15 (0.17) v 1.52 (0.29). Intensity ratios were higher in the 17 patients who underwent magnetic resonance imaging more than 72 hours after the onset of symptoms than in the 10 who underwent magnetic resonance imaging earlier, the difference being significantly greater after administration of Gd-DTPA (1.38 (0.12) v 1.61 (0.34). When patients were classified according to the site and size of the infarcted areas, or to reperfusion (n = 19) versus non-reperfusion (n = 8), the intensity ratios both before and after Gd-DTPA did not show significant differences. Magnetic resonance imaging with Gd-DTPA improved the identification of acutely infarcted areas, but with current techniques did not identify patients in whom thrombolytic treatment was successful.     

STIR-EPI序列在良恶性肺结节鉴别诊断中应用分析

目的探讨磁共振快速反转恢复-平面回波成像(STIR-EPI)序列在良恶性肺结节鉴别诊断中的应用价值。方法在我院就诊的肺结节患者中选取120例,所有患者均行MRI检查以及病理检测。测定肺结节信号强度评分、ADC值、SNR值。结果 120例肺结节患者中,良性结节41例,恶性结节79例。良性与恶性肺结节信号强度评分、ADC值、SNR值之间均有显著差异(P0.05)。结论 STIR-EPI序列可作为肺结节定性诊断的重要参考指标之一。     

Diagnostic significance of gadolinium-DTPA (diethylenetriamine penta-acetic acid) enhanced magnetic resonance imaging in thrombolytic treatment for acute myocardial infarction: its potential in assessing reperfusion.

The diagnostic value of gadolinium-DTPA (diethylenetriamine penta-acetic acid) enhanced magnetic resonance imaging in patients treated by thrombolysis for acute myocardial infarction was assessed in 27 consecutive patients who had a first acute myocardial infarction (14 anterior, 13 inferior) and who underwent thrombolytic treatment and coronary arteriography within 4 hours of the onset of symptoms. Magnetic resonance imaging was performed 93 hours (range 15-241) after the onset of symptoms. A Philips Gyroscan (0.5 T) was used, and spin echo measurements (echo time 30 ms) were made before and 20 minutes after intravenous injection of 0.1 mmol/kg gadolinium-DTPA. In all patients contrast enhancement of the infarcted areas was seen after Gd-DTPA. The signal intensities of the infarcted and normal values were used to calculate the intensity ratios. Mean (SD) intensity ratios after Gd-DTPA were significantly increased (1.15 (0.17) v 1.52 (0.29). Intensity ratios were higher in the 17 patients who underwent magnetic resonance imaging more than 72 hours after the onset of symptoms than in the 10 who underwent magnetic resonance imaging earlier, the difference being significantly greater after administration of Gd-DTPA (1.38 (0.12) v 1.61 (0.34). When patients were classified according to the site and size of the infarcted areas, or to reperfusion (n = 19) versus non-reperfusion (n = 8), the intensity ratios both before and after Gd-DTPA did not show significant differences. Magnetic resonance imaging with Gd-DTPA improved the identification of acutely infarcted areas, but with current techniques did not identify patients in whom thrombolytic treatment was successful.     

Serial imaging of canine myocardial infarction by in vivo nuclear magnetic resonance

Anterior infarction was produced in eight dogs to characterize serial changes in nuclear magnetic resonance signal intensity within the infarct zone. Magnetic resonance imaging was done on the day of infarction, on day 4, 5 or 6, on day 13 and day 20 using a 0.15 tesla (6.25 MHz) resistive imager. Electrocardiographically triggered spin echo (30, 45 and 60 ms echo times) and inversion recovery (400 to 500 ms inversion time) pulse sequences were employed to obtain single slice images. On day 20, the excised hearts were sectioned and examined to determine infarct location and extent. In the spin echo images, signal intensity within the ischemic zone was visibly increased in seven of the eight dogs on the day of infarction, and in all dogs by days 4 to 6. Signal intensity remained elevated in all but two dogs at day 20. With inversion recovery imaging, changes in the infarct zone were highly variable; both ill defined increases and decreases in signal intensity were noted. With a 30 ms echo time, signal intensity in the infarct zone was increased on average 29.8 +/- 24.1% above that in normal myocardium on the day of infarction. The relative signal intensity increased to 62.4 +/- 23.5% during the first 2 weeks after infarction (p less than 0.05), then decreased to 12.0 +/- 18.5% by day 20 (p less than 0.05). Similar changes were detected in the images using the 45 and 60 ms echo times. Nuclear magnetic resonance imaging therefore is able to detect regions of myocardial infarction and follow evolutionary changes in signal intensity within the infarct zone with healing.