骨关节炎动物模型中^99Tc^m-枸橼酸的生物分布特征及其代谢研究

目的：利用骨关节炎动物模型观察^99Tc^m-枸橼酸的生物分布和在骨关节炎症区域的代谢特点。方法：在制作骨关节炎动物模型的基础上，经在体显像及其感兴趣区技术计算器官和炎症关节的放射性活度的变化，同时也利用动物模型离体的测量器官或组织的百分注射量，分析^99Tc^m-枸橼酸在各器官和骨关节炎症区域的代谢特点。结果：^99Tc^m-枸橼酸的蛋白结合率为(17．01&;#177;0．75)％，骨关节炎症区域对^99Tc^m-枸橼酸有较高的摄取，骨关节炎的患／健比值出现在注射示踪剂后的30min到1h之间：在体显像患／健比值分别为4．120&;#177;0．552和3．150&;#177;0．587；百分注射量靶／非靶比值分别为3．279&;#177;0．463和3．899&;#177;0．125。^99Tc^m-枸橼酸主要经泌尿系统捧出。但也有少量是经肝脏一肠道系统捧出。结论：^99Tc^m-枸橼酸有较低的蛋白结合率，是急性骨关节炎良好的显像剂，其最佳显像时间为注射^99Tc^m-枸橼酸后的1h。     

家兔膝关节骨关节炎动物模型的建立

【目的】建立一个与人膝关节软骨损伤伴半月板损伤相似的骨关节炎的动物模型。【方法】通过在家兔后腿膝关节的股骨内髁关节面部位用骨钻造成其关节软骨的损伤,同时切除半月板。以后按一定时间取出其股骨髁,用内眼、光镜及电镜观察破损部软骨修复情况。【结果】家兔后腿膝关节股骨内髁关节面的关节软骨损伤后,有纤维软骨修复,但无透明软骨出现。与人膝关节软骨损伤后的修复情况相似。【结论】实验性兔关节面软骨损伤的病理变化机制,可作为研究人膝关节损伤致骨关节炎的动物模型。     

兔膝骨关节炎合并骨质疏松症动物模型的建立

背景：临床发现同时患有骨质疏松症和骨关节炎患者占相当大的比例,而且目前对骨质疏松与骨关节炎相互关系的认识不一致。目的：建立骨关节炎合并骨质疏松症的动物模型。方法：将14只新西兰大白兔随机等分为模型组和正常组。模型组新西兰大白兔行双侧卵巢切除,正常组新西兰大白兔不作任何处理。结果与结论：去除卵巢10周后,模型组大白兔关节软骨出现明显的退变,血清雌二醇、股骨骨密度水平较正常组显著下降（P〈0.01）,而关节软骨Mankin评分比正常组显著增高（P〈0.01）;且软骨Mankin评分与骨密度和血清雌二醇呈负相关,而骨密度与血清雌二醇水平呈正相关,表明实验成功建立了兔膝骨关节炎合并骨质疏松症动物模型。     

兔膝骨关节炎合并骨质疏松症动物模型的建立

背景:临床发现同时患有骨质疏松症和骨关节炎患者占相当大的比例,而且目前对骨质疏松与骨关节炎相互关系的认识不一致。目的:建立骨关节炎合并骨质疏松症的动物模型。方法:将14只新西兰大白兔随机等分为模型组和正常组。模型组新西兰大白兔行双侧卵巢切除,正常组新西兰大白兔不作任何处理。结果与结论:去除卵巢10周后,模型组大白兔关节软骨出现明显的退变,血清雌二醇、股骨骨密度水平较正常组显著下降(P<0.01),而关节软骨Mankin评分比正常组显著增高(P<0.01);且软骨Mankin评分与骨密度和血清雌二醇呈负相关,而骨密度与血清雌二醇水平呈正相关,表明实验成功建立了兔膝骨关节炎合并骨质疏松症动物模型。     

Ⅱ型胶原预防和治疗骨关节炎的动物实验

目的:采用H ulth法对新西兰兔建立膝骨关节炎动物模型,以透明质酸钠及注射用生理盐水为对照,观察Ⅱ型胶原注射治疗兔膝关节炎的愈合效果。方法:实验于2002-02/2003-07在暨南大学医学院附属第四医院完成。取36只新西兰兔制备Hulth膝骨关节炎动物模型,随机等分为3组:实验组术前及术后每两周关节内注射1m L1%Ⅱ型胶原至12周。关节内注射透明质酸钠组和关节内注射生理盐水组分别于术前及术后每两周关节内注射1%透明质酸钠1m L,生理盐水1m L,以上各组于术后4,8,12周各处死动物4只,作标本手术显微镜观察和组织学检测。结果:①实验组与透明质酸钠组骨关节炎改变较生理盐水对照组明显减轻。②术后4周时,实验组软骨膜光滑,软骨细胞排列整齐,可见双核软骨细胞;关节内注射透明质酸钠组软骨膜也光滑,软骨细胞排列整齐;关节内注射生理盐水组软骨膜细胞增生,有裂隙,软骨层变薄,细胞排列不规则。术后8周时,实验组软骨膜细胞增生,有裂隙,软骨细胞层次减少,但排列尚规则;关节内注射透明质酸钠组的光镜改变基本与实验组相似;关节内注射生理盐水组出现软骨表面缺损及纤维化,软骨细胞层薄排列不规则。术后12周时,实验组、关节内注射透明质酸钠组的光镜改变与实验组术后8周时相似;关节内注射生理盐水组在其术后8周时光镜改变基础上有更广泛的软骨缺损,部分切片可见软骨下骨质暴露。结论:①Ⅱ型胶原与透明质酸钠匀能有效抑制骨关节炎。②外源性Ⅱ型胶原可以替代透明质酸钠应用于骨关节炎的防治。     

中药熏药护理方案对骨关节炎大鼠模型的影响

骨关节炎是一种常见的中老年疾病。西医治疗主要以服用镇痛药物和非甾体消炎药对症、缓解疼痛为主,虽然能短时间缓解疼痛,但是副反应较多、作用不持久。我院中医科多年来采用骨痹方熏蒸治疗骨关节病,疗效确切,受到广大病人欢迎。但在熏蒸过程中由于护理操作尚无统一标准,随意性强,使其作用效     

以关节不稳建立的大鼠骨关节炎模型

背景：骨性关节炎是一种复杂的多病因退变性关节疾病。早期进行骨性关节炎的防治尤其重要。但获取足量的适合研究的早期骨性关节炎的人类骨标本十分困难。目的：观察关节不稳方法建立骨关节炎模型大鼠的关节软骨组织学变化。方法：10周龄雄性SD大鼠随机分为2组：实验组切除右膝内侧半月板及内侧副韧带,对照组仅切开关节囊。于术后1,2,4,6,8周取右膝关节标本,行病理组织学检查分析大鼠骨关节炎病程的变化情况。结果与结论：①术后2,4,6,8周,实验组关节软骨退变程度呈现轻度糜烂、溃疡磨损、严重磨损、骨赘形成等病理变化。②术后1,2,4,6,8周,实验组关节软骨评分均明显高于对照组（P〈0．05）。结果显示该实验采用内侧副韧带切断＋内侧半月板切除方法成功建立了大鼠膝关节骨关节炎模型,且造模后4周内的病理、形态学改变类似于人类早期膝关节骨关节炎表现,是研究早期骨关节炎的理想模型。     

外用伤骨科Ⅱ号治疗骨关节炎的实验研究

为研制的外用伤骨科Ⅱ号临床治疗骨关节炎提供动物实验资料，并为开发外用伤骨科Ⅱ号应用于骨科临床病人提供理论依据，以实施以下动物研究实验。报告如下。     

动脉血栓靶向超声显像的体内实验研究

目的探讨白蛋白血栓靶向超声造影剂体内增强动脉血栓超声显像的效果.方法采用FeCl3溶液诱发30只健康新西兰大白兔腹主动脉非梗阻性新鲜血栓形成;经耳缘静脉团注0.04 ml/kg的白蛋白超声造影剂进行超声造影,分为靶向组(20只)和非靶向组(10只);采用视觉观察评价血栓显像增强效果.结果 29只(29/30)兔模型建立成功;造影后视觉观察,靶向组18例达到2级增强效果,1例为1级增强效果,1例死亡;非靶向组仅2例达到1级增强效果,两组比较差异显著(P<0.01).结论白蛋白血栓靶向超声造影剂可显著增强兔腹主动脉内新鲜血栓超声显像效果.     

一种新的肾脏功能显象剂^99mTc—Bz—MAG3药盒的制备和动物实验

本文报道~(99m)T_C—B_Z—MAG_3药盒的制备方法和动物实验。制备药盒时,以10ml生理盐水溶解200mg葡萄糖酸钙,用0.25N的HCl调节pH5.5,依次加入B_Z—MAG_3 10mg和SnCl_2·2H_2 O200μg,G_4细菌漏斗过滤,分装成1ml/瓶,置-30℃储存或冷冻干燥后放4℃冰箱保存。本药盒加入~(99m)T_C O_4 -0.5～3ml,液态和冻干品药盒的标记率均>95％。该药盒具有肾浓聚快、排泄迅速以及无毒性、无热源、无细菌等特点,使用是非常安全的。     

Methionine metabolism in an animal model of sepsis

BACKGROUND: Sepsis is a disease with high incidence and lethality and is accompanied by profound metabolic disturbances. In mammalian methionine metabolism, S-adenosylmethionine (SAM) is produced, which is important in the synthesis of neurotransmitters and glutathione and as an anti-inflammatory agent. The degradation product and antagonist of SAM is S-adenosylhomocysteine (SAH). In this study, we investigated changes in methionine metabolism in a rodent model of sepsis. METHODS: Sepsis was induced in male Wistar rats (n=21) by intraperitoneal injection of bacterial lipopolysaccharide (10 mg/kg). Controls (n=18) received vehicle only. Blood was collected by cardiac puncture 24 h later. Puncture of the suboccipital fossa was performed to collect cerebrospinal fluid (CSF). Methionine metabolites were measured using stable isotope dilution tandem mass spectrometry. Plasma total homocysteine and cysteine were measured by HPLC using fluorescence detection. Glutathione was assayed using a modified enzymatic microtiter plate assay. RESULTS: We observed significantly higher plasma levels of SAM (p<0.001) and SAM/SAH ratio (p=0.004) in septic animals. In CSF, there was also a trend for higher levels of SAM in septic animals (p=0.067). Oxidative stress was reflected by an increase in the ratio of oxidized/reduced glutathione in septic animals (p=0.001). CONCLUSIONS: Sepsis is associated with an increase in SAM/SAH ratio in plasma and CSF in rodents. This indicates an altered methylation potential during sepsis, which may be relevant for sepsis-associated impairment of transmethylation reactions, circulation and defense against oxidative stress. If verified in humans, such findings could lead to novel strategies for supportive treatment of sepsis, as methionine metabolism can easily be manipulated by dietary strategies.     

An animal model for measuring the effect of common NICU procedures on ATP metabolism

Neonates exposed to common neonatal intensive care unit (NICU) procedures show alterations in heart rate, blood pressure, and oxygen saturation. However, it is unclear if these physiologic changes increase adenosine triphosphate (ATP) utilization, thus potentially increasing the risk for tissue hypoxia in medically fragile neonates. Plasma uric acid is a commonly used marker of increased ATP utilization because uric acid levels increase when ATP consumption is enhanced. To examine the effect of a common NICU procedure on plasma uric acid concentration, we developed a model that allows for acute monitoring of this biochemical marker in plasma in 7- to 9-day-old rabbits. In our pilot study, we exposed neonatal rabbits to a single heel lance 2.5 hr after catheter placement. We measured uric acid concentration before and 30 min after the heel lance and compared findings to levels in control animals not exposed to the heel lance. Our pilot data shows a significant difference in uric acid concentration over time between the control and heel lance groups (46.2 ± 7.1 μM vs. 54.7 ± 5.8 μM, respectively, p = .027). Calculation of percentage change from baseline showed uric acid concentration increasing in rabbits exposed to heel lance and decreasing in control rabbits (1.5 ± 4.7% vs. -16.1 ± 4.2%, respectively, p = .03). These data suggest that this animal model can be successfully used to examine the biochemical effect of common NICU procedures, such as heel lance, on markers of ATP breakdown and purine metabolism.     

Brain tissue oxygen pressure and cerebral metabolism in an animal model of cardiac arrest and cardiopulmonary resuscitation

OBJECTIVE: Direct measurement of brain tissue oxygenation (PbtO2) is established during spontaneous circulation, but values of PbtO2 during and after cardiopulmonary resuscitation (CPR) are unknown. The purpose of this study was to investigate: (1) the time-course of PbtO2 in an established model of CPR, and (2) the changes of cerebral venous lactate and S-100B. METHODS: In 12 pigs (12-16 weeks, 35-45 kg), ventricular fibrillation (VF) was induced electrically during general anaesthesia. After 4 min of untreated VF, all animals were subjected to CPR (chest compression rate 100/min, FiO2 1.0) with vasopressor therapy after 7, 12, and 17 min (vasopressin 0.4, 0.4, and 0.8 U/kg, respectively). Defibrillation was performed after 22 min of cardiac arrest. After return of spontaneous circulation (ROSC), the pigs were observed for 1h. RESULTS: After initiation of VF, PbtO2 decreased compared to baseline (mean +/- SEM; 22 +/- 6 versus 2 +/- 1 mmHg after 4 min of VF; P < 0.05). During CPR, PbtO2 increased, and reached maximum values 8 min after start of CPR (25 +/- 7 mmHg; P < 0.05 versus no-flow). No further changes were seen until ROSC. Lactate, and S-100B increased during CPR compared to baseline (16 +/- 2 versus 85 +/- 8 mg/dl, and 0.46 +/- 0.05 versus 2.12 +/- 0.40 microg/l after 13 min of CPR, respectively; P < 0.001); lactate remained elevated, while S-100B returned to baseline after ROSC. CONCLUSIONS: Though PbtO2 returned to pre-arrest values during CPR, PbtO2 and cerebral lactate were lower than during post-arrest reperfusion with 100% oxygen, which reflected the cerebral low-flow state during CPR. The transient increase of S-100B may indicate a disturbance of the blood-brain-barrier.     

生长抑素受体显像剂99mTc-HYNIC-TOCA和99mTc-P829在肿瘤模型中的对比研究

目的:研究99mTc标记的生长抑素类似物(somatostatin analogues,SSA)99mTc-6-肼基烟酰基-[Tyr3[-Octreotate(99mTc-HYNIC-TOCA)在肿瘤动物模型体内的生物学特性,并与99mTc-P829对比,探讨其用于肿瘤诊断的可行性。方法:以HYNIC为双功能螯合剂(bifunctional chelator,BFC),乙二胺-N?熏N’-二乙酸(EDDA)和三(羟甲基)甲基甘氨酸(Tricine)为协同配体进行TOCA的99mTc标记;以99mTc-HYNIC-TOCA和99mTc-P829为显像剂,对荷人类小细胞肺癌裸鼠进行显像,通过感兴趣区(ROI)技术进行半定量分析,计算并比较两种显像剂的靶/非靶(T/NT)比值;在昆明鼠体内进行动态生物学分布实验,测定并比较不同时点两种显像剂在各脏器的克组织百分摄取率(%ID/g)。结果:99mTc-HYNIC-TOCA的放化纯可达94.2%,室温放置6h后放化纯仍为93.5%;荷瘤小鼠体内,99mTc-HYNIC-TOCA和99mTc-P829主要浓聚于肾脏和肿瘤部位。早期显像中,99mTc-HYNIC-TOCA组肿瘤与对侧比值(T/C)均高于99mTc-P829组;4h时平面显像中T/C达到最高,分别为7.45±0.40和5.71±0.69。昆明鼠体内,两种显像剂在肾脏的摄取率最高,血液半清除时间均小于60min;肝脏对99mTc-P829的最大摄取率明显高于99mTc-HYNIC-TOCA(t=2.17,P<0.05)。结论:99mTc-HYNIC-TOCA和99mTc-P829均具有肿瘤摄取高和血液清除快的良好生物学特性,在高表达SSTR肿瘤的定位诊断中有良好的应用前景。     

抑郁症动物模型研究进展

抑郁症临床上可单发或继发于脑卒中等疾病之后,由于其发病机制至今尚未完全清楚,给抑郁症动物模型的研制带来很大的困难。应激动物模型,神经生化功能改变模型及孤养和分养模型等是目前常用的动物模型,但只表现出抑郁症的某些方面症状。转基因动物模型是一类很有希望的动物模型,能够比较全面地表现出抑郁症症状,逐渐成为抑郁症动物模型研究的热点。     

宫内感染致早产鼠脑瘫动物模型制备及其鉴定的实验研究

目的：探索宫内感染致早产鼠脑性瘫痪动物模型的制备方法，并对脑瘫动物模型进行鉴定。方法：脑瘫动物模型的制备：给予16只孕16、17天的实验组大鼠脂多糖每次350μg/kg，连续2天腹腔注射，8只对照组孕鼠腹腔注射同剂量的生理盐水。观察两组孕鼠的分娩时间及新生仔鼠出生体重。孕22天前分娩的仔鼠为早产鼠。将实验组中提前分娩的母鼠和对照组母鼠处死后，取子宫和胎盘HE染色观察。模型鉴定：①神经行为学检测：30日龄早产鼠16只，足月产鼠30只，分别进行随意运动障碍、姿势异常、肌张力异常、不自主动作、情感行为能力及倾斜板试验，记录各项评分并进行统计学处理；②病理学检测：30日龄早产鼠16只，足月产鼠16只，断头取脑，光镜与电镜下观察脑组织变化。结果：①实验组有6只大鼠提前分娩，共获活早产仔鼠26只；对照组均为足月分娩，产仔鼠74只、早产仔鼠出生后颜色青紫、活动少、体重低；②子宫及胎盘病理检测可见提前分娩母鼠子宫壁及胎盘内血管充血、水肿，并见大量中性粒细胞浸润；③16只30日龄早产鼠中，10只经鉴定为脑瘫鼠。④脑瘫大鼠随意运动障碍，姿势、肌张力异常，病理结果显示脑损伤部位在白质，系胶质细胞、髓鞘的损伤。结论：①孕鼠腹腔注射LPS可诱发早产；②LPS致宫内感染可成功制备早产鼠脑瘫动物模型；③脑瘫鼠具有冲经行为学异常；④脑瘫鼠动物模型的病理改变以白质损伤为主。     

利用免疫缺陷动物构建骨肉瘤动物模型研究进展

骨肉瘤是骨组织最常见的原发性恶性肿瘤,恶性程度很高且青少年多发,目前其机制尚不明确,故构建一个生物学行为和药物动力学接近人骨肉瘤的动物模型是深入研究该疾病发病机制、寻找靶向性和特异性更高的新治疗手段的重要途径。免疫缺陷动物是先天性遗传突变或人工方法造成的一种多系统免疫功能缺陷动物,裸鼠因其无胸腺和T细胞缺如的免疫缺陷特点,使移植性肿瘤仍能保留其原有的生物学特性,成为直接研究人类骨肉瘤生物学特性及其发病机制的重要研究手段。现就近年免疫缺陷动物的骨肉瘤动物模型建立作一综述。     

A finite element model of the shoulder: application to the comparison of normal and osteoarthritic joints

Objective. The objective of the present study was to develop a numerical model of the shoulder able to quantify the influence of the shape of the humeral head on the stress distribution in the scapula. The subsequent objective was to apply the model to the comparison of the biomechanics of a normal shoulder (free of pathologies) and an osteoarthritic shoulder presenting primary degenerative disease that changes its bone shape.

Design. Since the stability of the glenohumeral joint is mainly provided by soft tissues, the model includes the major rotator cuff muscles in addition to the bones.

Background. No existing numerical model of the shoulder is able to determine the modification of the stress distribution in the scapula due to a change of the shape of the humeral head or to a modification of the glenoid contact shape and orientation.

Methods. The finite element method was used. The model includes the three-dimensional computed tomography-reconstructed bone geometry and three-dimensional rotator cuff muscles. Large sliding contacts between the reconstructed muscles and the bone surfaces, which provide the joint stability, were considered. A non-homogenous constitutive law was used for the bone as well as non-linear hyperelastic laws for the muscles and for the cartilage. Muscles were considered as passive structures. Internal and external rotations of the shoulders were achieved by a displacement of the muscle active during the specific rotation (subscapularis for internal and infrapinatus for external rotation).

Results. The numerical model proposed is able to describe the biomechanics of the shoulder during rotations. The comparison of normal vs. osteoarthritic joints showed a posterior subluxation of the humeral head during external rotation for the osteoarthritic shoulder but no subluxation for the normal shoulder. This leads to important von Mises stress in the posterior part of the glenoid region of the pathologic shoulder while the stress distribution in the normal shoulder is fairly homogeneous.

Conclusion. This study shows that the posterior subluxation observed in clinical situations for osteoarthritic shoulders may also be cause by the altered geometry of the pathological shoulder and not only by a rigidification of the subscapularis muscle as often postulated. This result is only possible with a model including the soft tissues provided stability of the shoulder.

Relevance One possible cause of the glenoid loosening is the eccentric loading of the glenoid component due to the translation of the humeral head. The proposed model would be a useful tool for designing new shapes for a humeral head prosthesis that optimizes the glenoid loading, the bone stress around the implant, and the bone/implant micromotions in a way that limits the risks of loosening.     

Small animal PET for the evaluation of an animal model of genital infection

Background: [¹⁸F]‐FDG is a widely used tracer for the non‐invasive evaluation of hypermetabolic processes like cancer and inflammation. However, [¹⁸F]‐FDG is considered inaccurate for the diagnosis of urinary tract and genital infections because of its urinary excretion. Since the 1970s, Gallium scintigraphy is a well established test that has been used for the evaluation of inflammation and infection in human patients. Aim: The aim of this study was to assess the feasibility of ⁶⁸Ga‐Chloride small animal PET for the analysis of an animal model of genital infection, induced after the vaginal inoculum of Chlamydia muridarum. Material and methods: Thirty mice were infected by placing 15 μl of sucrose phosphate glutamic acid (SPG) 10⁷ inclusion forming units of C. muridarum into the vaginal vault. As controls of inflammation, three animals were challenged with 15 μl of SPG and one healthy animal was used to assess the tracer biodistribution. Four animals died during the experiment. Eleven animals were evaluated with ⁶⁸Ga‐Chloride small animal PET (GE, eXplore Vista) 3–5, 10–12, 17–19 days after infection, as well as three controls of inflammation and one healthy animal. Infection was monitored by obtaining cervical‐vaginal swabs from all the animals on the day of each PET procedure. Moreover, five groups of three animals each were killed at 6, 13, 20, 27 and 34 days after infection were studied. Results: ⁶⁸Ga‐PET turned out positive in all the infected animals, concordantly to data obtained by the cervical swabs and by the ex vivo analysis. The tumour‐to‐background ratio (TBR) decreased over time as the inflammation tended to naturally extinguish. The controls showed a slightly increased uptake of tracer due to the aseptic inflammation caused by SPG and frequent cervical swabs. The healthy control did not show any pelvic uptake. Conclusion: ⁶⁸Ga‐Chloride is a promising tracer for the assessment of genital infection in a mouse animal model.