CN111387137A - 一种建立大鼠出血性关节炎实验模型的方法及应用 - Google Patents
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Abstract
本发明公开了一种建立大鼠出血性关节炎实验模型的方法及应用,属于医疗技术领域,该建立大鼠出血性关节炎实验模型的方法及应用,结合血友病和关节炎因素,对临床出血性关节炎进行高效模拟,建立了一种和临床血友病性关节炎发病较相似的新型动物模型,通过选取FVIII基因敲除的雄性大鼠模型,能够确保实验模型的准确性,再经过人工手术关节处损伤的制备,快速的建立出血性关节炎实大鼠验模型,且新模型可通过时间点与不同时期的模型进行对比,为进一步研究该病的发病机制,研发新的治疗措施与产品奠定了的重要的动物模型评价基础。
Description
技术领域
本发明属于医疗技术领域,具体为一种建立大鼠出血性关节炎实验模型的方法及应用。
背景技术
血友病是一组以三高(出血率高、死亡率高、致残率高)为特征的遗传性出血性疾病。出血是血友病生之俱生,伴随终生,最主要的症状和致残(血肿压迫神经、血管致残、关节炎畸形致残)、致死的主要原因。血友病关节病变是血友病最常见的临床表现,反复发作,致残率高达80%以上。自1869年首次从血友病关节抽出积血以来,至今临床医生普遍认为血友病关节肿痛是关节出血所致,常规应用凝血因子Ⅷ/Ⅸ制剂治疗血友病出血和关节病变,但随之而来的是血液病毒(艾滋和肝炎病毒)感染及凝血因抗体(抑制物)产生,灭活患者自身凝血因子98%活性,加重出血、死亡和致残率。
目前现代医学采用FⅧ/FⅨ替代疗法已应用了半个多世纪,但血友病致残率仍高达80%以上。其原因:因为血友病关节病变和血肿的形成,与免疫介导性炎症有关,而凝血因子只有止血作用,没有免疫抑制抗炎作用,当然对血友病免疫介导性关节炎和血肿疗效差。血友病的血肿,常属多发性,手术切除后易复发。总之,目前现代医学缺乏有效方法。中医学的膏剂多属辛辣刺激品或活血、破血之类,均不适用于血友病关节和血肿。
因此需要研究对血友病性关节炎有效的新疗法,在研究治疗血友病性关节炎药物时,实验模型的建立也具有了重要意义。
发明内容
(一)解决的技术问题
为了克服现有技术的上述缺陷,本发明提供了一种建立大鼠出血性关节炎实验模型的方法及应用,解决了上述背景技术中所提出的问题。
(二)技术方案
为实现上述目的,本发明提供如下技术方案:
一种建立大鼠出血性关节炎实验模型的方法,所述建立方法如下:
a选取八周龄、体重为两百克左右的FVIII基因敲除雄性大鼠模型,静脉注射适量凝血因子,然后按37.5mg/1000g用苯巴比妥钠麻醉,观察大鼠呼吸情况;
b选取大鼠右膝关节,进行常规备皮消毒,取髌旁内侧进行切口,使膝关节显露,显露髌骨后将髌骨向外侧脱位,尽量屈曲膝关节显露前交叉韧带,切断前交叉韧带,行抽屉试验确认前交叉韧带已完全切断;
c手术创口使用无菌生理盐水冲洗干净后,用纱布处理手术部位,将外脱位的髌骨复位,进行缝合,术后每天进行肌肉注射青霉素20万单位预防感染,同时静脉注射适量凝血因子加快伤口恢复速度,再将大鼠分组编号后分笼进行饲养,让其自由活动;
d术后三天大鼠疼痛缓解后,进行适应性饲养三到五天,通过普通饲养喂养,自由进食,饮料为自来水,适应性饲养同时进行适应性运动,适应期结束后密切观察大鼠的生命体征、活动和饮食等情况,同时观察关节变化情况;
e适应期结束后一周,大鼠关节明显肿胀,局部皮肤温度增高,运动受限,关节呈保护性僵直状态,患处解剖后在显微镜下观察关节面处发生出血,关节面粗糙,有较小裂隙;
f适应期结束后两周,大鼠关节肿胀,运动受限,伴有摩擦音,患处解剖后在显微镜下观察关节内反复出血、关节囊及滑膜增厚;
一种建立大鼠出血性关节炎实验模型的应用,上述建立方法所建立的出血性关节炎大鼠模型可用于制备出血性关节炎药物研究的模型。
(三)有益效果
与现有技术相比,本发明的有益效果在于:该建立大鼠出血性关节炎实验模型的方法及应用,结合血友病和关节炎因素,对临床出血性关节炎进行高效模拟,建立了一种和临床血友病性关节炎发病较相似的新型动物模型,通过选取FVIII基因敲除的雄性大鼠模型,能够确保实验模型的准确性,再经过人工手术关节处损伤的制备,快速的建立出血性关节炎实大鼠验模型,且新模型可通过时间点与不同时期的模型进行对比,为进一步研究该病的发病机制,研发新的治疗措施与产品奠定了的重要的动物模型评价基础。
具体实施方式
下面结合具体实施方式对本专利的技术方案作进一步详细地说明。
本发明提供一种技术方案:一种建立大鼠出血性关节炎实验模型的方法,所述建立方法如下:
a选取八周龄、体重为两百克左右的FVIII基因敲除雄性大鼠模型,静脉注射适量凝血因子,然后按37.5mg/1000g用苯巴比妥钠麻醉,观察大鼠呼吸情况;
b选取大鼠右膝关节,进行常规备皮消毒,取髌旁内侧进行切口,使膝关节显露,显露髌骨后将髌骨向外侧脱位,尽量屈曲膝关节显露前交叉韧带,切断前交叉韧带,行抽屉试验确认前交叉韧带已完全切断;
c手术创口使用无菌生理盐水冲洗干净后,用纱布处理手术部位,将外脱位的髌骨复位,进行缝合,术后每天进行肌肉注射青霉素20万单位预防感染,同时静脉注射适量凝血因子加快伤口恢复速度,再将大鼠分组编号后分笼进行饲养,让其自由活动;
d术后三天大鼠疼痛缓解后,进行适应性饲养三到五天,通过普通饲养喂养,自由进食,饮料为自来水,适应性饲养同时进行适应性运动,适应期结束后密切观察大鼠的生命体征、活动和饮食等情况,同时观察关节变化情况;
e适应期结束后一周,大鼠关节明显肿胀,局部皮肤温度增高,运动受限,关节呈保护性僵直状态,患处解剖后在显微镜下观察关节面处发生出血,关节面粗糙,有较小裂隙;
f适应期结束后两周,大鼠关节肿胀,运动受限,伴有摩擦音,患处解剖后在显微镜下观察关节内反复出血、关节囊及滑膜增厚;
一种建立大鼠出血性关节炎实验模型的应用,上述建立方法所建立的出血性关节炎大鼠模型可用于制备出血性关节炎药物研究的模型。
该建立大鼠出血性关节炎实验模型的方法及应用,结合血友病和关节炎因素,对临床出血性关节炎进行高效模拟,建立了一种和临床血友病性关节炎发病较相似的新型动物模型,通过选取FVIII基因敲除的雄性大鼠模型,能够确保实验模型的准确性,再经过人工手术关节处损伤的制备,快速的建立出血性关节炎实大鼠验模型,且新模型可通过时间点与不同时期的模型进行对比,为进一步研究该病的发病机制,研发新的治疗措施与产品奠定了的重要的动物模型评价基础。
上面对本专利的较佳实施方式作了详细说明,但是本专利并不限于上述实施方式,在本领域的普通技术人员所具备的知识范围内,还可以在不脱离本专利宗旨的前提下作出各种变化。
Claims (2)
1.一种建立大鼠出血性关节炎实验模型的方法,其特征在于:所述建立方法如下:
a选取八周龄、体重为两百克左右的FVIII基因敲除雄性大鼠模型,静脉注射适量凝血因子,然后按37.5mg/1000g用苯巴比妥钠麻醉,观察大鼠呼吸情况;
b选取大鼠右膝关节,进行常规备皮消毒,取髌旁内侧进行切口,使膝关节显露,显露髌骨后将髌骨向外侧脱位,尽量屈曲膝关节显露前交叉韧带,切断前交叉韧带,行抽屉试验确认前交叉韧带已完全切断;
c手术创口使用无菌生理盐水冲洗干净后,用纱布处理手术部位,将外脱位的髌骨复位,进行缝合,术后每天进行肌肉注射青霉素20万单位预防感染,同时静脉注射适量凝血因子加快伤口恢复速度,再将大鼠分组编号后分笼进行饲养,让其自由活动;
d术后三天大鼠疼痛缓解后,进行适应性饲养三到五天,通过普通饲养喂养,自由进食,饮料为自来水,适应性饲养同时进行适应性运动,适应期结束后密切观察大鼠的生命体征、活动和饮食等情况,同时观察关节变化情况;
e适应期结束后一周,大鼠关节明显肿胀,局部皮肤温度增高,运动受限,关节呈保护性僵直状态,患处解剖后在显微镜下观察关节面处发生出血,关节面粗糙,有较小裂隙;
f适应期结束后两周,大鼠关节肿胀,运动受限,伴有摩擦音,患处解剖后在显微镜下观察关节内反复出血、关节囊及滑膜增厚。
2.一种建立大鼠出血性关节炎实验模型的应用,其特征在于:权利要求1中所述的建立方法所建立的出血性关节炎大鼠模型可用于制备出血性关节炎药物研究的模型。
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