膝关节腔内注射皮质类固醇对关节软骨损害的研究——病理组织…

３０只健康新西兰白兔，随机分为两组，每组１５只，Ａ组右膝关节腔内注射醋酸强的松龙，每次７．５ｍｇ／ｋｇ，每周１次，Ｂ组右膝关节内注射生理盐水，每次０．３７５ｍｌ／ｋｇ，每周１次，每组分别于第３，５，７，９，１１周的第１天，各取３只动物，在光镜下观察双侧膝关节和股骨头软骨标本有无病理组织学改变，并在第５，９，１１周加作超微结构观察，结果显示Ａ组用药２次后即双侧股骨头，膝关节软骨下区髓内脂肪细胞增多，     

维丁胶性钙预防关节腔内注射皮质类固醇引起骨关节的损害

目的：采用维丁胶性钙预防关节内注射皮质类固醇对骨关节的损害。方法：４５只健康新西兰白兔，随机分为三组，每组１５只。Ａ组：右膝关节内注射醋酸强的松龙７．５ｍｇ／ｋｇ。Ｂ组：用药同Ａ组，同时每周肌注维丁胶性钙三次，每次１ｍｌ。Ｃ组：右膝关节内注射生理盐水０．３７５ｍｌ／ｋｇ，作为对照。于实验的第３、５、７、９、１１周的第１天，每组取３只动物作髋关节和膝关节Ｘ光照片，并取膝关节及股骨头标本作病理组织学和超微结构检查。结果：Ａ组。用药２次后，Ｘ线照片、病理组织学检查和超微结构观察均有骨关节损害的表现，并随给药次数的增加而加重。Ｂ组。用药６次后才出现轻度病理组织学和超微结构改变。Ｃ组。各项指标均正常。从而证实维丁胶性钙有预防或减轻皮质类固醇所致骨关节损害的作用。结论：在疼痛治疗中，关节内注射皮质类固醇应尽量减少注射次数和延长间隔时间，并同时应用维丁胶性钙肌注有一定预防骨质损害作用。     

膝关节腔内注射皮质类固醇对骨髓腔内压的影响

３０只健康新西兰白兔，随机分为Ａ，Ｂ两组，每组１５只，Ａ组右膝关节内注射醋酸强的松龙７．５ｍｇ／ｋｇ，每周１次；Ｂ组右膝关节内注射生理盐水０．３７５ｍｌ／ｋｇ，每周１次，每组分别于第３，５，７，９，１１周的第１天，各取３只动物，在氯胺酮麻醉下，行双侧胫骨上端，股骨下端和膝关节腔穿刺，并测定腔内压力。     

关节内注射皮质类固醇对肝功能及血脂的影响

目的:观察关节内注射皮质类固醇对肝功能和血脂的影响。方法:30只健康新西兰白兔随机分为2组,每组15只。A组动物右膝关节腔内注射醋酸强的松龙7.5mg/kg,每周1次。B组动物右膝关节腔内注射生理盐水0.375ml/kg,每周1次。所有动物每周称体重并检查皮下脂肪分布情况1次。于实验前及实验第3、5、7、9、11周的第1天,抽血3ml进行血清总胆固醇、甘油三酯、谷丙转氨酶及血钙含量测定。同时取肝组织在光镜下进行病理组织学检查。结果:A组动物在用药2次后,皮下脂肪减少,体重减轻,血清胆固醇、甘油三酯和谷丙转氮酶增高,血清钙含量下降,且随用药次数的增加而变化明显(P<0.01)。病理组织学检查发现用药4次后即出现肝脂变,且随用药次数的增加而加重。B组动物在整个的实验过程,体重增加,血脂、血钙含量正常,肝功能及肝组织无异常改变。结论:关节内注射皮质类固醇同全身用药一样,可造成脂肪代谢紊乱,血钙含量下降及肝功能损害。     

关节内注射糖皮质激素对关节软骨影响的实验研究

目的：探讨关节内注射糖皮质激素的剂量与给药次数对关节软骨的影响。方法：选择健康白兔25只并随机5组,分别向关节内注射0.1ml,0.2ml及0.4ml醋酸泼尼松龙2次或4次。对照组膝关节内注射等容量的生理盐水,注射完成2周后对动物关节软骨进行组织学观察及电镜检查,结果：实验组关节软骨表面不规则、缺损、裂隙及结构破坏,软骨细胞数目增多或减少以及软骨异染性的降低。潮线的完整性破坏。软骨细胞超微结构发生改变,包括软骨细胞肿胀。水肿变性及坏死。结论：关节软骨的损伤程度与注射糖皮质激素的剂量及给药次数有关。     

肝细胞生长因子对关节软骨缺损修复作用的实验研究

目的 探讨肝细胞生长因子＊ｈｅｐａｔｏｃｙｌｅ ｇｒｏｗｔｈ ｆａｃｔｏｒ,ＨＧＦ）对创伤性关节软骨损伤的修复作用。方法 选 用大耳白 兔２５只,随机分成５组,每组５只。在两侧髌股关节股骨侧的关节面中心分别造成直径３．５ｍｍ的全层关节软骨缺损。造反右侧为实验组,自术后起,膝关节内注射１０μｇ／ｍｌ的ＨＧＦ０．１ｍｌ,每周３次,共４周;左侧为对照组,与实验组同一时间注射等量生理盐水。于术后４、６、８     

前凝血状况与激素性股骨头缺血坏死的相关性研究

研究前凝血状况与激生股骨头缺血坏死是否存在相关性,从而进一步探讨激素导致股骨头缺血坏死的发病机理。方法选中国大白兔２０只,体重２．８±０．７ｋｇ,随机将其分为３组。Ａ组：７只,静脉内注射大鼠菌内毒素,共２次,每次１００ｕｇ／ｋｇ,间隔２４小时,在第２交无大肠杆菌内毒素后随即肌肉注射甲基强的松共３次,每次２０ｍｇ／ｋｇ,间隔２４小时。Ｂ组：１０只,单纯肌肉注射甲基强的松龙,共３次,每次２０ｍｇ／ｋｇ     

河蚌葡聚糖HBP-A对豚鼠膝关节软骨退变的影响

[目的]观察关节内注射不同剂量河蚌葡聚糖（anodonta glucan, HBP-A）对豚鼠膝关节软骨退变及相关标志物的影响。[方法]豚鼠20只随机分为五组,分别为正常组、模型组、低浓度组、中浓度组和高浓度组,每组4只。正常组行右膝假手术处理,其余动物均行右膝前交叉韧带切断,建立骨性关节炎模型。术后3 d,正常组和模型组右膝关节内注射生理盐水,而低、中、高剂量组分别注射7.5 mg/ml、15 mg/ml、30 mg/ml的HBP-A 200μl,每周注射1次,连续5周。5周后处死动物,取右膝关节标本行组织学、免疫组织化学和q PCR检测。[结果]组织学观察见,与正常组相比,模型组出现显著软骨退变,而注射HBP-A组织结构显著改善。模型组较正常组OARSI评分显著增加（P<0.05）,在给予低、中、高浓度HBP-A关节腔注射,OARS评分呈剂量依赖性显著降低（P<0.05)。免疫组化方面,模型组较正常组软骨ALP、Ihh、Runx2和MMP13的OD值显著升高（P<0.05）,而低、中、高浓度HBP-A关节注射软骨ALP、Ihh、Runx2和MMP13的OD值呈剂量...     

关节镜治疗膝关节骨性关节炎的护理

１９９８年１月至２００１年６月期间，本院对２４例膝关节骨性关节炎患者采用了膝关节镜治疗，取得了满意疗效。现将护理经验报告如下。临床资料１．一般资料：本组男１０例，女１４例；年龄３６～７３岁，病程：０．５～９年。右膝９例，左膝１５例，均有膝关节肿痛。X线片均显示膝关节骨质增生，关节间隙稍变窄，软骨下骨质致密。住院时间７～１５天，平均１１天。２．手术方法：２４例均在手术室连续硬膜外麻醉下进行。手术切口前外侧入路（AL），在髌腱外侧１cm，外侧半月板前角上方（或关节间隙上方１cm），将膝关节屈曲３０°，切…     

创伤后关节软骨细胞凋亡及其预防的实验研究

目的探讨关节软骨创伤后软骨细胞凋亡情况及其预防方法。方法32只新西兰大白兔,4只行膝关节囊切开,不损伤软骨(正常组),另28只双侧膝关节钻孔造成软骨急性损伤,一侧关节腔在术毕和术后每周1次注射1％透明质酸钠1 mL(治疗组),另一侧不做处理作为损伤对照(损伤组);利用TUNEL、流式细胞仪两种方法检测软骨受损区软骨细胞凋亡情况。结果损伤后软骨细胞出现坏死和凋亡,至第4天软骨细胞凋亡率最大,凋亡细胞全层分布;透明质酸钠治疗组软骨细胞凋亡较损伤组明显减少,差异有极显著性意义(P<0．01)。结论创伤后关节软骨细胞发生凋亡会导致创伤后骨关节炎的发生。早期关节腔内注射透明质酸钠能有效抑制软骨细胞凋亡,可能对预防和降低创伤后骨关节炎的发生有重要意义。     

透明质酸载碱性成纤维细胞生长因子对兔膝关节缺血再灌注损伤防治作用的实验研究

目的：通过动物实验观察碱性成纤维细胞生长因子(bFGF)与透明质酸(HA)关节腔内注射对关节缺血再灌注损伤及退行性关节炎的防治作用。方法：采用夹闭兔股血管8h的方法模拟缺血再灌注模型。将48只新西兰大白兔随机分为对照组(A组)，HA治疗组(B组)和FGF／HA治疗组(C组)，在关节腔内注射相应的药物。用光镜和电镜观察关节滑膜和软骨的病理改变，观察并半定量计算软骨蛋白多糖(PGs)的变化，检测滑膜丙二醛(MDA)的含量。结果：C组的软骨和滑膜病理改变明显轻于A组和B组，在C组中，滑膜MDA的含量明显低于其它两组，而PGs的含量明显高于其它两组：结论：联合应用bFGF和HA能明显减轻兔膝关节缺血再灌注损伤和退行性改变，其作用要明显优于单用HA。     

The effect of hyaluronan combined with microfracture on the treatment of chondral defects: an experimental study in a rabbit model

Because articular hyaline cartilage has low potential for regeneration, numerous methods and techniques have been proposed to induce the reparation process. Microfracture is a convenient procedure for this purpose. However, the quality of the new cartilage after microfracture is still not as proper as original. In this experimental study, we used microfracture in combination with intraarticular application of hyaluronan in rabbit knee articular defect. Bilateral knee arthrotomies, chondral defects, and microfracture were created on each intercondylar notch in thirty rabbits. Rabbits received intraarticular injections of hyaluronan once a week for 3 weeks in the right knee, started from 1 week after injury. The left knees, which served as controls, were injected with normal saline. Biopsy was taken from both knees at the 4th and 6th weeks. In comparison with the control group, after 6 weeks we observed a higher potential for healing in the experimental group, with thicker and more organized repair tissue filling the defect. The current study reveals that application of hyaluronan after the microfracture might be beneficial in inducing articular cartilage defect reparation.     

The effect of bone remodeling inhibition by zoledronic acid in an animal model of cartilage matrix damage

OBJECTIVE: The purpose of this work was to test the effect of inhibition of bone remodeling, through the use of the bisphosphonate, zoledronic acid, on cartilage matrix damage in an animal model of cartilage matrix damage. DESIGN: New Zealand white rabbits were divided into four groups for treatment purposes: (1) untreated controls; (2) injected into one knee joint with the cartilage matrix degradation enzyme, chymopapain; (3) injected into one knee joint with chymopapain and also given subcutaneous injections of the bisphosphonate, zoledronic acid, three times per week until sacrifice at either day 28 or 56 post-chymopapain-injection; (4) received only the zoledronic acid injections. At sacrifice, the knee joints were examined grossly and histologically, and biochemically for proteoglycan content. Urine samples were analysed, at intervals, for levels of collagen cross-links which are biochemical markers of cartilage and bone. RESULTS: Animals receiving both intraarticular chymopapain injections and subcutaneous zoledronic acid injections displayed a significantly lower degree of grossly and histologically detectable cartilage degeneration on the tibial articular surfaces (the articular surface displaying the greatest degree of degeneration) than did animals only receiving the chymopapain injections. In addition, urinary levels of collagen cross-links for bone and cartilage were significantly higher in those animals only receiving chymopapain injections. CONCLUSION: The bone resorption observed after chymopapain injection into the rabbit knee joint can be inhibited through the use of the bisphosphonate, zoledronic acid. Furthermore, zoledronic acid does not increase the level of cartilage degeneration and appears to provide some level of chondroprotection in this model.     

Hyaluronic acid attenuates osteoarthritis development in the anterior cruciate ligament-transected knee: Association with excitatory amino acid release in the joint dialysate.

We previously reported increased release of the excitatory amino acid (EAA) neurotransmitters, glutamate and aspartate, during the early stage of experimental osteoarthritis (OA). Our present objective was to study the effect of intraarticular injection of hyaluronic acid (HA) on OA development, and to analyze concomitant changes in EAA levels in dialysates of anterior cruciate ligament-transected (ACLT) knee joints. OA was induced in Wistar rats by ACLT of one hindlimb; the knee of the other hindlimb was used as the sham-operated control. HA group (n = 12) were injected intraarticularly in the ACLT knee with 1 mg of HA once a week for 5 consecutive weeks, starting at 8 weeks after surgery. Saline group (n = 12) were injected as above with normal saline. The sham-operated group, underwent arthrotomy, but not ACLT, and received no treatment (n = 14). Twenty weeks after surgery, knee joint dialysates were collected by microdialysis and EAA levels assayed by high-performance liquid chromatography, and gross morphological examination and histopathological evaluation were performed on the medial femoral condyles and synovia. Rats receiving intraarticular HA injections showed a significantly lower degree of cartilage degeneration on the medial femoral condyle at both the macroscopic level and on the Mankin grading scale than rats receiving saline injections. Intraarticular HA treatment also suppressed synovitis. Moreover, glutamate and aspartate levels were significantly reduced in the HA group compared to the saline group. Intraarticular injection of HA limits articular cartilage and synovium damage and OA formation, and, in parallel, reduces EAA levels in ACLT joint dialysates. This study suggests that the underlying mechanism of the anti-inflammatory effect of HA is to inhibit glutamate and aspartate release in ACLT knee joints, which attenuates the early development of OA.     

丹参和透明质酸钠局部给药对兔骨关节炎的影响

目的探讨丹参和透明质酸钠局部给药对兔膝骨关节炎(OA)模型的影响。方法建立Hulth兔膝OA动物模型。每周经膝关节穿刺给药1次,观察丹参和透明质酸钠单用或合用对兔膝关节组织形态学、滑膜丙二醛(MDA)含量及血红细胞超氧化物歧化酶(SOD)比活性的影响。结果丹参或透明质酸钠单用和合用组均能显著降低兔膝关节大体软骨分级评分和镜下Mankin’s分级评分(P<0.01),尤以合用组作用最佳;同时丹参单用或与透明质酸钠合用组还明显增加红细胞SOD比活性(103%,158%),减少滑膜MDA生成量(66%,77%)。结论丹参和透明质酸钠局部注射对OA有治疗作用,尤以合用时显著。     

川芎嗪防治膝关节软骨退变的实验研究

目的 :应用膝关节制动的动物模型 ,探讨中药川芎嗪对膝关节OA软骨退变的保护作用。方法 :2 4只健康成年家兔 ,随机分为两组 ,每组 12只 ,动物的右后肢采用膝关节伸直位管形石膏制动的方法建立骨性关节炎模型。实验组膝关节注射川芎嗪 0 3ml,每周 1次 ,对照组注射 0 3ml生理盐水 ,每周 1次 ,在模型建立 6、9周时 ,每组分别取 6只动物 ,进行超氧化物歧化酶 (SOD)、丙二醛 (MDA)、糖胺多糖 (GAG)含量测定 ,并观察滑膜、软骨的病理改变。结果 :实验组MDA的浓度低于对照组的浓度 ,两者差异有显著性 (6周 ,P <0 0 5 ;9周 ,P <0 0 1) ,6周时 ,对照组的GAG含量明显上升 ,与正常组及实验组相比 ,均有显著性差异 (P <0 0 1)。实验组SOD浓度在不同时期均高于对照组 (6周 ,P <0 0 5 ;9周 ,P <0 0 1)。光镜观察可见 ,实验组滑膜和软骨病理改变较对照组轻。结论 :川芎嗪对早期膝关节OA的软骨退变具有保护作用     

The effect of hyaluronic acid on a rabbit model of full-thickness cartilage repair

The current study investigated whether hyaluronate exerts a beneficial effect on articular cartilage repair. Nineteen rabbits had bilateral knee arthrotomies, and 2-mm full-thickness cartilage defects were created on each medial femoral condyle. Rabbits received intraarticular injections (0.5 mL) of hyaluronic acid once a week for 3 weeks in the right knee, started at either 1 or 3 weeks after injury. The left knees, which served as controls, were injected with 0.5 mL normal saline. Cohorts of each group were euthanized at 2 and 6 months, and histologic sections of the injury sites were evaluated for repair tissue. No significant differences were seen in the quantity or quality of the repair tissue at either 2 or 6 months. Hyaluronate and saline-treated defects showed persistent fibrillation, poor matrix staining, and incomplete void filling, irrespective of the injection timing. Hyaluronate did not provide protection to zones peripheral to the injury site, and did not significantly alter the healing process in this model of acute full-thickness cartilage injuries.     

不同浓度木瓜蛋白酶建立兔膝骨关节炎模型的比较研究

目的:比较不同浓度木瓜蛋白酶建立的兔膝骨关节炎模型,为研究骨关节炎病理及诊疗方法提供数据支持。方法:将60只新西兰大耳白兔随机分为4组,分别在1、3、5d右膝关节腔注射2%(低剂量组)、5%(中剂量组)、10%(高剂量组)(w/v)木瓜蛋白酶和0.03mol/L的L-半胱氨酸混合溶液0.1ml/kg(实验组),以及等量生理盐水(对照组)。整个实验过程观察兔状态并记录体重和膝关节宽度。首次注射后第2、4、6周将兔分批处死,取股骨髁、胫骨平台及滑膜做大体及组织病理学观察,并进行评分。结果:实验组均出现关节宽度增大、关节软骨变薄、基质分解破坏、滑膜增生等炎症及退行性改变,严重程度随浓度增高而增高,也随时间延长而发展;对照组无上述改变,二者比较差异有统计学意义。结论:兔膝骨关节腔注射2%、5%、10%木瓜蛋白酶和0.03mol/LL-半胱氨酸混合溶液0.1ml/kg可制备不同严重程度的骨关节炎模型,周期短,可重复且成功率高。