高分子绷带结合塑料杆建立的兔膝骨关节炎模型

BACKGROUND: Various methods have been developed for establishing a rabbit osteoarthritis model worldwide. However, most of modeling methods are cumbersome, and the original gypsum braking method has some defects.     

去势兔骨质疏松模型建立的初探

选用兔作模型进行探索，以期证明兔原发性骨质疏松动物模型建立的可行性。通过切除双侧卵巢的方法诱发兔骨质疏松动物模型的建立，术后５－８个月内观察其骨密度，体重，毛色及生长状况，处死后取骨作生物力不测定，病理组织学检查，烧灰测灰重及灰的钙，磷含量，观察其子宫重。     

沙浴治疗兔膝骨关节炎的实验研究

目的：研究沙浴对兔膝关节骨性关节炎(osteoarthritis OA)关节周围血流、膝关节滑膜及软骨的病理改变的影响，为中老年人膝骨关节炎的沙浴治疗提供依据。方法：青紫兰兔15只，成功建立OA动物模型13只，其中12只随机分成自由活动组(A)，自由活动加沙疗组(B)，健侧关节沙疗对照组(C)。在平均气温32℃情况下，将模型兔下半部分掩埋在干燥的40～50℃的海沙中，1次25～30min，1次／d。观察沙疗后即时的膝关节周围血流情况，以及经过沙疗10d和20d后膝关节滑膜及软骨的病理改变。结果：沙疗后患侧膝关节活动改善，膝关节周围血管内血流明显增加，膝关节滑膜细胞层次逐渐减少、炎症细胞明显减少，但软骨细胞退变改善在光学显微镜下不明显。结论：沙疗能增加治疗部位的血流，改善局部血液循环，促进炎症的消退，对正常关节无不利影响。     

手术诱导膝骨关节炎兔模型的制备方法

背景：目前常用的膝骨关节炎动物模型制备方法主要有手术创伤和关节腔内注射蛋白酶诱导两大类。关节腔内注射药物诱导模型并不稳定,传统的手术造模方法对膝关节损伤较大,且成模过程与临床膝骨关节炎的发展过程差异较大。目的：通过不同手术方式损伤膝关节制备兔膝骨关节炎模型,探讨膝骨关节炎动物模型的最佳制备方法。方法：将16只雄性五六月龄新西兰大白兔随机分为假手术组、模型A组、模型B组、模型C组,每组4只。假手术组切开右侧膝关节内侧后立即缝合;模型A组磨损右侧膝关节半月板、磨损前交叉韧带;模型B组摘除右侧膝关节半月板、磨损前交叉韧带;模型C组摘除右侧膝关节半月板、切断前交叉韧带。术后连续3 d注射抗生素,记录一般情况。4周后通过X射线片观察关节情况,苏木精-伊红染色观察软骨组织变化,酶联免疫吸附法检测右侧膝滑膜液和血清中炎症因子水平。结果与结论：(1)模型组右侧膝关节明显出现红肿热痛情况,皮温明显高于假手术组;(2)术后模型组右侧膝关节皮温较假手术组明显升高,差异有显著性意义(P <0.05);(3)X射线片显示假手术组膝关节未见异常,模型组出现不同程度的关节面破坏及关节间隙狭窄,其中模型C组最为...     

慢性肺动脉血栓栓塞动物模型的建立

背景：目前国内外接近人体生理学的慢性肺动脉血栓栓塞的动物模型较少见。 目的：采用自体血栓反复注射法建立慢性肺动脉血栓栓塞的动物模型。 方法：将家兔随机分为栓塞组和假栓塞组,栓塞组家兔肺动脉多次注入自体血栓,假栓塞组用生理盐水替代血栓。 结果与结论：栓塞组干预4周后解剖肺动脉并经病理检测可发现有血栓机化,肺动脉CT造影均可见局部肺动脉截断征,以及炎症、梗死、胸膜增厚等间接征象,肺动脉解剖及病理均可发现实验兔肺动脉血栓形成机化及慢性炎症改变。结果证实,采用兔自体血栓反复注射法可成功建立慢性肺血栓栓塞动物模型。     

兔适合构建鼻窦炎动物模型

背景：以实验动物模拟人类相关疾病是研究疾病发生发生及治疗的基础,鼻腔、鼻窦疾病也需要恰当实验动物作为其模型。 目的：观察兔鼻腔、鼻窦的CT和局部解剖表现,探讨兔应用于鼻窦炎动物模型的可行性。 方法：利用CT使用常规鼻窦冠状位与水平位扫描新西兰兔,随后进行常规鼻腔、鼻窦解剖学观察。 结果与结论：兔鼻中隔将鼻腔分为左右两个腔,鼻腔外侧壁由上颌鼻甲、中间鼻甲、内侧鼻甲、下鼻甲组成,上颌窦窦腔最大,筛窦、蝶窦、额窦相对较小,以上结构均对称分布。兔鼻腔、鼻窦在CT扫描下显示清晰。兔鼻腔、鼻窦的解剖与人类鼻腔、鼻窦解剖结构既有相似也有不同,其上颌窦解剖部位与人相似且窦腔较大便于操作,具有动物实验模型建立的可行性,适用于鼻窦炎动物模型建立,可应用于模拟人类鼻窦炎的研究。 中国组织工程研究杂志出版内容重点：肾移植;肝移植;移植;心脏移植;组织移植;皮肤移植;皮瓣移植;血管移植;器官移植;组织工程全文链接：     

木瓜蛋白酶诱导膝关节骨关节炎模型兔滑膜病理变化与药物注射时间的关系

背景：木瓜蛋白酶诱导兔膝关节骨性关节炎的造模方法可获得稳定的退行性关节炎模型。 目的：观察兔膝关节腔内注射木瓜蛋白酶诱导骨关节炎后,滑膜炎性病理改变与药物注射时间的关系。 方法：将木瓜蛋白酶水溶液分别在实验开始的第1,4,7天分别注射入15只西兰大白兔右膝关节腔内,建立膝关节骨性关节炎兔模型,于首次注射后第2,4,6周分别观察膝关节滑膜大体及组织病理学变化,每个时间点5只。 结果与结论：木瓜蛋白酶首次注射后第2周,兔膝关节滑膜炎性反应最严重,表现为滑膜细胞增生最明显,下层疏松纤维及血管组织明显增生,可见较多淋巴浆细胞浸润,第4,6周时炎性反应逐渐减轻。说明兔膝关节首次注射木瓜蛋白酶后2周时滑膜炎性反应最严重。     

兔膝骨关节炎成纤维样滑膜细胞分离培养方法的研究

目的 在传统细胞组织块培养方法的基础上进行改进,建立一种简单、可重复性操作的兔膝骨关节炎成纤维样滑膜细胞分离培养方法。方法 通过手术诱导建立兔膝骨关节炎模型,在无菌条件下,快速取出兔膝骨关节炎的滑膜组织,经过冲洗处理后剪成一定大小碎片,用无菌滤纸吸净组织上附着的水分,接种在培养皿后,进行观察、换液、传代、拍照。将原代培养的细胞传至第三代细胞接种于96孔板中,采用噻唑蓝（MTT）法分别在不同时间梯度检测各孔对应吸光度,制作生长曲线;采用免疫荧光染色法观察细胞中波形蛋白的表达情况。结果 培养的细胞为典型的梭形,符合成纤维样滑膜细胞的生长形态特征,免疫荧光染色显示波形蛋白强表达。结论 改进后的组织块培养方法简单、操作可重复性强,可以获得大量兔膝骨关节炎成纤维样滑膜细胞,为后续膝骨关节炎的机理研究提供了大量细胞支持。     

骨关节炎的转基因动物模型

背景：近年来随着转基因技术的发展,出现了骨关节炎的转基因动物模型,表明不同基因的缺失与突变都可能导致骨关节炎,这将为骨关节炎的药物筛选试验和治疗提供新方案。 目的：对骨关节炎的转基因动物模型的构建及其相关机制进行概述,为防治骨关节炎奠定理论基础。 方法：第一作者应用计算机检索1995/2010 PubMed数据库相关文章,检索词为“transgenic animal models,Osteoarthritis”,并限定文章语言种类为English。同时计算机检索2000/2010 中国知网数据库相关文章,检索词为“转基因动物模型,骨关节炎”并限定文章语言种类为中文。共检索到文章158 篇,最终纳入22篇。 结果与结论：骨关节炎转基因动物模型在研究骨关节炎起始机制、关节软骨生化改变和防治效果的比较等方面具有明显优势;排除了手术创伤及炎症对骨关节炎模型软骨、滑膜的生化代谢的影响;同时也减轻了模型动物的痛苦。为药物筛选试验和治疗提供新方案。     

温阳益髓中药干预兔膝骨关节炎软骨基质金属蛋白酶的表达

背景：目前临床上关于温阳益髓中药治疗膝骨关节炎对软骨基质金属蛋白酶表达影响的研究还较少有报道。 目的：制作兔膝骨关节炎模型观察温阳益髓中药对软骨基质金属蛋白酶表达的影响。 方法：健康成年新西兰大白兔96只,随机选取72只采用石膏外固定方法制作兔膝骨关节炎模型。确定造模成功后再随机分为3组,模型组不做处理;中药治疗组每日灌胃方药提取液24 mL/kg,药物对照组每日灌胃葡立胶囊(盐酸氨基葡萄糖)24 mg/kg,1次/d,至造模成功后8周。另外24只新西兰大白兔作为空白对照。 结果与结论：PCR方法定量分析骨关节炎模型组软骨组织中基质金属蛋白酶1、基质金属蛋白酶3、基质金属蛋白酶13表达水平均显著高于其他3组。中药治疗组及药物对照组中基质金属蛋白酶1、基质金属蛋白酶3及基质金属蛋白酶13的表达较模型组明显降低。说明温阳益髓中药治疗兔膝骨关节炎能够有效抑制兔骨关节炎软骨基质金属蛋白酶的表达。 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程全文链接：     

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。     

肾虚血瘀型膝骨性关节炎大鼠模型的建立

背景：建立骨性关节炎的中医证候模型,有利于对其进行辨证施治研究。 目的：采用病、证结合的方法建立肾虚血瘀型膝骨关节炎大鼠模型。 方法：选择2月龄雌性SPF 级SD大鼠30只,随机分为正常组、膝骨关节炎组和复合模型组,每组10 只。采用经典的Hulth造模法建立膝骨关节炎模型,去卵巢法建立肾虚模型,肾上腺皮质激素和肾上腺素法建立血瘀模型。复合模型由上述3种模型复合而成,先建立肾虚模型,8周后同时进行血瘀模型与骨关节炎模型造模。 结果与结论：复合模型组大鼠在肾虚模型建立后第3周时出现精神萎靡、活动不灵活、便溏等表现,在血瘀模型建立后第6周时大鼠出现皮毛无光泽、喜背光、舌质瘀紫、尾色及爪甲瘀青,体质量下降;低切还原黏度增高,血小板聚集性增强等血流缓慢、循环障碍特点;组织学染色观察发现膝骨关节炎组关节软骨结构有一定破坏但轻于复合模型组。可见实验成功建立了大鼠肾虚血瘀型大鼠膝骨关节炎模型,而肾虚血瘀加重了膝骨关节软骨的退变。     

Clinical outcomes of knee joint distraction combined with marrow stimulation procedures for patients with advanced knee osteoarthritis

BackgroundKnee joint distraction (KJD) has received much attention as a joint preserving surgery, especially in young patients with advanced knee osteoarthritis (OA).MethodsThis study included 16 patients with advanced knee OA who underwent KJD combined with marrow stimulating techniques and were followed up for more than 2 years. The patients’ clinical scores, including the Japanese Orthopaedic Association (JOA) score, Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales, ROM, joint space width, and semiquantitative MRI were evaluated. The factors affecting clinical outcomes were analyzed.ResultsPostoperatively, the JOA score and the individual scores of the KOOS subscales improved significantly (JOA score: P = 0.0028, KOOS-symptoms: P = 0.0016, -pain: P = 0.0011, -ADL: P = 0.0009, -sports/recreation: P = 0.0144, and -QOL: P = 0.0034). Although the extension of the knee joint did not change throughout the follow-up period, flexion of the joint deteriorated at the time of device removal but recovered to the preoperative level at the final follow-up. Preoperative joint space width was 2.4 ± 2.0 mm and at the final follow-up, it increased to 3.3 ± 1.5 mm, showing statistically significant improvement (P = 0.034). The postoperative semiquantitative MRI score also improved significantly (from 6.0 ± 3.0 to 42.1 ± 28.7, P = 0.0001). A high BMI was associated with a poor clinical outcome.ConclusionAlthough the effect of marrow stimulating techniques for cartilage repair was not well clarified and the complication rate was high, the clinical and radiographic outcomes showed significant improvement after KJD combined with marrow stimulating techniques in patients with advanced knee OA. However, we should be careful about suggesting this procedure in obese patients.     

Carrageenan-induced transient inflammation in a rabbit knee model: molecular changes consistent with an early osteoarthritis phenotype

Objective

Inflammation following a knee injury is one of the factors associated with initiation of cartilage degeneration leading to osteoarthritis (OA). The hypothesis tested was that inflammation results in elevated expression of proteinases implicated in OA.

Methods

Mature female rabbits received a single carrageenan injection to the right hind knee and the left knee served as the control. Five animals were killed at time points of 1, 2 and 4?weeks. The synovium and cartilage from both knees were collected and analysed for specific mRNA levels.

Results

Interleukin (IL)-1β and IL-6 mRNA levels peaked at 2?weeks and returned to normal levels in tissues by 4?weeks post-carrageenan treatment. Matrix metalloproteinase (MMP)-13, MMP-1, MMP-3 and cathepsin K followed the trend set by the inflammatory cytokines. Both synovium and cartilage tissues exhibited similar patterns of molecular expression, with cartilage from the tibial plateau responding more strongly than the femoral condyles.

Conclusions

The acute inflammatory milieu controls the transient expression of many degradative proteinases in the knee. However, a single acute exposure to inflammation in the rabbit knee is insufficient to create a chronic inflammatory environment and other complementary factors, such as persistent mechanical instability and/or injury, may contribute to the establishment of OA.     

Miao medicine fumigation can delay extracellular matrix destruction in a rabbit model of knee osteoarthritis

BACKGROUND: Previous studies have shown that Miao medicine fumigation therapy has a definite effect on the treatment of osteoarthritis;however, its mechanism is unclear. Because excessive angiogenesis in synovial tissue and subchondral bone tissue is an important cause of the occurrence and development of osteoarthritis, vascular endothelial growth factor is an important pro-angiogenesis factor in the body, and the stromal cell-derived factor 1/CXCR4 signaling pathway is closely related to the overexpression of vascular endothelial growth factor. OBJECTIVE: To explore the role of stromal cell-derived factor 1/CXCR4 signaling pathway in the osteoarthritic occurrence and development and the therapeutic mechanism of Miao medicine fumigation on knee osteoarthritis. METHODS: Fifty healthy New Zealand white rabbit were randomized into normal, model, positive control (voltaren ointment for external use), early intervention, and Miao medicine fumigation groups. The knee osteoarthritis model was established in the latter four groups by injecting sodium iodoacetate into the knee joint cavity of rabbits. Hematoxylin-eosin staining was used to observe the pathological changes of synovium and cartilage. Immunohistochemical method was used to detect the levels of interleukin-1β and tumor necrosis factor-α in synovial tissue. ELISA method was used to detect the level of stromal cell-derived factor 1 in synovial fluid and the level of vascular endothelial growth factor in serum. Real-time fluorescence quantitative PCR was used to detect vascular endothelial growth factor mRNA expression in articular cartilage tissue. Western blot assay was used to detect the expression of type II collagen and aggrecan protein in cartilage tissue. RESULTS AND CONCLUSION: Compared with the model group, Miao medicine fumigation treatment significantly inhibited the inflammation in synovium and cartilage tissue and reduced its pathological changes. Compared with the model group, the integral absorbance values of interleukin-1β and tumor necrosis factor-α in synovium and the levels of vascular endothelial growth factor in serum and stromal cell-derived factor in joint fluid were significantly reduced in the Miao medicine fumigation group (P < 0.05). Compared with the model group, the serum vascular endothelial growth factor mRNA was reduced in the Miao medicine fumigation group, while type II collagen and aggrecan expressions were increased (P < 0.05). The above experimental results indicated no significant differences among Miao medicine fumigation group, positive control group and early intervention group (P > 0.05). To conclude, the Miao medicine fumigation therapy maybe by reducing the binding of stromal cell-derived factor 1 to its receptor CXCR4 inhibits the expression of interleukin-1β, tumor necrosis factor-α, and vascular endothelial growth factor, delays the destruction of extracellular matrix, and plays a therapeutic role. © 2022, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.     

Predicting dynamic knee joint load with clinical measures in people with medial knee osteoarthritis

Knee joint loading, as measured by the knee adduction moment (KAM), has been implicated in the pathogenesis of knee osteoarthritis (OA). Given that the KAM can only currently be accurately measured in the laboratory setting with sophisticated and expensive equipment, its utility in the clinical setting is limited. This study aimed to determine the ability of a combination of four clinical measures to predict KAM values.Three-dimensional motion analysis was used to calculate the peak KAM at a self-selected walking speed in 47 consecutive individuals with medial compartment knee OA and varus malalignment. Clinical predictors included: body mass; tibial angle measured using an inclinometer; walking speed; and visually observed trunk lean toward the affected limb during the stance phase of walking. Multiple linear regression was performed to predict KAM magnitudes using the four clinical measures. A regression model including body mass (41% explained variance), tibial angle (17% explained variance), and walking speed (9% explained variance) explained a total of 67% of variance in the peak KAM.Our study demonstrates that a set of measures easily obtained in the clinical setting (body mass, tibial alignment, and walking speed) can help predict the KAM in people with medial knee OA. Identifying those patients who are more likely to experience high medial knee loads could assist clinicians in deciding whether load-modifying interventions may be appropriate for patients, whilst repeated assessment of joint load could provide a mechanism to monitor disease progression or success of treatment.     

富血小板血浆修复膝关节骨关节炎

BACKGROUND: Platelet-rich plasma (PRP) containing high levels of platelet-derived growth factor for knee osteoarthritis has achieved good clinical results; however, the effects of RPR on the repair of damaged articular cartilage are still controversial. OBJECTIVE: To study the effects of RPR on the repair of damaged articular cartilage in a rabbit model of knee osteoarthritis. METHODS:The model of osteoarthritis in the rabbit right knee was established by Hulth’s method. Autologous PRP (0.5 mL) (PRP group), sodium hyaluronate (0.5 mL) (sodium hyaluronate group), and normal saline (model group) were injected into the right knee joint cavity, respectively. The morphology of articular surface and nitric oxide contents in knee joint fluid were observed and determined at 8 weeks after surgery. RESULTS AND CONCLUSION: The morphology of articular cartilage in the PRP group was better than that in the other three groups. Mankin scores of articular cartilage and nitric oxide contents of knee joint fluid in the PRP group were significantly decreased compared with the model and sodium hyaluronate groups that in (P < 0.05), while increased compared with the sham-operation group (P < 0.05). Our results suggest that repair effects of PRP on the damaged articular cartilage are superior to sodium hyaluronate treatment. 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

选择性切断膝关节神经支对膝骨性关节炎模型兔关节软骨超微结构的影响

目的观察选择性切断膝关节神经支对兔膝骨性关节炎模型关节软骨超微结构的影响。方法采用Huhh法复制兔膝骨性关节炎模型,通过外科显微镜下选择性切断兔膝关节神经支,对关节软骨等结构进行形态学观察,运用TUNEL法检测软骨细胞的凋亡,并应用透射电镜观察关节软骨超微结构的变化。结果模型组兔膝关节软骨出现退变的表现,软骨细胞过度凋亡,其凋亡指数（31．25±6．83）明显高于正常组（3．16±0．65;P〈0．05）。模型组关节软骨超微结构明显受损,软骨细胞出现核固缩,线粒体肿胀,粗面内质网扩张、脱颗粒;软骨基质内胶原纤维断裂溶解,结构模糊。治疗组兔膝关节软骨退变有明显改善,细胞凋亡指数（15．43±3．72）明显低于模型组（P〈0．05）,关节软骨超微结构较模型组有明显改善。结论选择性切断膝关节神经支对膝骨性关节炎模型兔关节软骨细胞凋亡有抑制作用,并能改善关节软骨的超微结构。     

富血小板血浆与透明质酸钠修复兔膝骨关节炎

 背景：研究表明,透明质酸钠可抑制膝骨关节炎对软骨的破坏,加速软骨细胞的再生,达到稳定和修复关节软骨的目的。目的：观察富血小板血浆与透明质酸钠治疗兔膝骨关节炎的疗效。方法：将40只新西兰大白兔随机均分为5组,联合组、玻璃酸钠组、富血小板血浆组与模型组制作右侧膝骨关节炎模型,造模后分别向膝关节腔内注射透明质酸钠联合自体富血小板血浆、玻璃酸钠、自体富血小板血浆与生理盐水进行治疗,1次/周,连续5周;对照组不做任何处理,为正常对照。治疗完成1周后,ELISA法检测血液中白细胞介素1、白细胞介素6、肿瘤坏死因子α水平,光镜下观察关节软骨的变化。结果与结论：与对照组比较,其余4组白细胞介素1、白细胞介素6、肿瘤坏死因子α水平均升高(P < 0.01);联合组、透明质酸钠组、富血小板血浆组白细胞介素1、白细胞介素6、肿瘤坏死因子α水平均低于模型组(P < 0.01或P < 0.05),且以联合组下降最显著。模型组关节软骨破坏明显,联合组、透明质酸钠组、富血小板血浆组关节软骨破坏程度轻于模型组,且以联合组破坏程度最轻。表明透明质酸钠配合自体富血小板血浆关节内注射可降低膝骨关节炎的炎症反应,保护关节软骨,效果优于单一药物注射。中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程