摘要
目的观察豚鼠原发性骨关节炎(OA)模型中疾病进展的相关病理改变,探究整合素α5β1对OA的关节软骨退变的初步作用,为OA的治疗提供参考。方法选取3周龄的SPF级Hartely雌性豚鼠24只,进行1周的适应性喂养并记录初始体重后对其进行编号,然后采用随机分配法将24只豚鼠分为基线组、对照组、ATN-161治疗组、盐水治疗组4组,每组6只。其中基线组豚鼠在实验开始时处死,对照组豚鼠正常饲养3月龄时处死,ATN-161豚鼠在正常饲养3个月后开始予以ATN-161腹腔注射1 mg/(kg·3 d)直至3个月后处死,生理盐水治疗组豚鼠在正常饲养3个月后开始予以生理盐水腹腔注射1 mg/(kg·3 d)直至3个月后处死。取所有处死豚鼠的膝关节软骨标本,对其进行苏木精-伊红(HE)染色,观察并使用Mankin评分评估软骨退变程度;记录免疫组织化学染色分析力学传导分子(整合素α5β1)、氧化应急指标观察[基质金属蛋白酶(MMP)-13]以及细胞凋亡指标(Bax、bcl-2)在软骨中的表达情况。结果HE染色组织学和Mankin评分结果显示,对照组豚鼠在3月龄时即发生了OA样改变,并且随着月龄的增长退变逐渐加重,通过ATN-161治疗后,ATN-161治疗组在6月龄时Mankin评分明显降低(P<0.05)。免疫组化结果证实,α5β1的表达在基线组与对照组之间差异无统计学意义(P>0.05),之后随着月龄的增加,生理盐水治疗组中整合素α5β1的表达高于对照组(P<0.05):与生理盐水治疗组比较,ATN-161组治疗后能明显降低整合素α5β1的表达(P<0.05);随着豚鼠月龄的增加,MMP-3在软骨中的表达增多,对照组明显高于BL组,生理盐水组显著高于对照组(P<0.05);细胞凋亡(Bax、bcl-2)免疫组化指标均显示:基线组、对照组、ATN-161治疗组三组之间差异有统计学意义(P<0.05)。其中Bax在对照组中表达量最低,基线组中最高,ATN-161组表达量明显高于生理盐水治疗组(P<0.05)。此外,bcl-2在对照组表达量�
Objective To observe the pathological changes related to disease progression in guinea pig primary osteoarthritis(OA)model,and to explore the preliminary effect of integrinα5β1 on articular cartilage degeneration of OA,so as to provide reference for the treatment of OA.Methods A total of 24 SPF-rated Hartely female guinea pigs aged three weeks were selected for adaptive feeding for a week and numbered after their initial weight was recorded.Then,the 24 guinea pigs were randomly divided into the baseline group,the control group,the ATN-161 treatment group,and the normal saline treatment group,with six in each group.The guinea pigs in the baseline group were killed at the beginning of the experiment,the guinea pigs in the control group were killed at three months of normal feeding,the guinea pigs in the ATN-161 were given intraperitoneal injection of 1 mg/(kg·3 d)ATN-161 after three months of normal feeding until three months of death,and the guinea pigs in the normal saline treatment group were given intraperitoneal injection of 1 mg/kg/3d normal saline after normal feeding for three months until they were killed after three months.Samples of knee cartilage from all the executed guinea pigs were stained with hematoxylin-eosin(HE),and the degree of cartilage degeneration was observed and evaluated by Mankin score.The expressions of mechanical-conduction molecules(integrinα5β1),oxidative emergency index observation(MMP-13)and apoptosis index(Bax,bcl-2)in cartilage were recorded by immunohistochemical staining.Results HE staining histology and Mankin score showed that OA-like changes occurred in guinea pigs in the control group at the age of three months,and the degeneration gradually worsened with the increase of age.After treatment with ATN-161,the ATN-161 treatment group significantly reduced Mankin score at six months of age(P<0.05).Immunohistochemical results confirmed that there was no significant difference inα5β1 expression between the baseline group and the control group(P>0.05).After that,with the in
作者
李远
李忠
刘俊才
LI Yuan;LI Zhong;LIU Juncai(Department of Joint Surgery,Suining Central Hospital,Suining,Sichuan 629099,China;Department of Orthopaedics,The Affiliated Hospital of Southwest Medical University/Sichuan Orthopaedic Placement Devices R&D and Application Technology Engineering Laboratory,Luzhou,Sichuan 646000,China)
出处
《现代医药卫生》
2023年第18期3082-3088,共7页
Journal of Modern Medicine & Health
基金
西南医科大学自然科学基金(青年)资助项目(2018-ZRQN-122)。
