关节腔内注射医用臭氧治疗颞下颌关节骨关节炎模型大鼠的合适剂量

An appropriate dose of intra-articular medical ozone injection in a rat model of temporomandibular joint osteoarthritis

背景:医用臭氧是臭氧与氧气的混合物,与体液接触能快速产生活性氧,并激活机体的抗氧化系统。在临床上,关节腔内注射医用臭氧可有效缓解骨关节炎的进展。目的:观察关节腔内注射医用臭氧对大鼠颞下颌关节骨关节炎的治疗作用。方法:采用关节腔内一次性注射碘乙酸钠法建立大鼠颞下颌关节骨关节炎模型后,向大鼠关节腔内注射质量浓度分别为20,30,40 mg/L医用臭氧,1次/周,连续注射3周,模型组及对照组注射等量生理盐水,最后一次注射后1周,通过锥形束CT检查评价颞下颌关节的结构变化,然后取一侧颞下颌关节组织并抽取腹主动脉血,ELISA法检测髁突软骨及血浆中肿瘤坏死因子α水平,取另一侧颞下颌关节组织,经苏木精-伊红染色及番红O-固绿染色,采用改良Mankin’s评分法评估颞下颌关节组织的病理变化程度。结果与结论:①锥形束CT观察结果:对照组大鼠颞下颌关节髁突形状规则,表面光滑;医用臭氧20,30 mg/L组大鼠髁突形变及表面缺损程度较模型组、医用臭氧40 mg/L组小;②ELISA法检测结果:与对照组相比,模型组、医用臭氧20,30,40 mg/L组大鼠髁突软骨及血浆中肿瘤坏死因子α表达水平显著升高(P<0.05);与模型组、医用臭氧40 mg/L组相比,医用臭氧20,30 mg/L组髁突软骨及血浆中肿瘤坏死因子α表达水平明显下降(P<0.05);③组织学观察结果:医用臭氧20,30,40 mg/L组及模型组改良Mankin’s评分均高于对照组(P<0.05),医用臭氧20,30 mg/L组改良Mankin’s评分低于模型组、医用臭氧40 mg/L组(P<0.05);④结果表明,关节腔内注射质量浓度分别为20,30 mg/L医用臭氧时,能明显缓解大鼠颞下颌关节骨关节炎的进展,但是当臭氧质量浓度上升到40 mg/L时,反而会加重大鼠颞下颌关节骨关节炎的病变程度。

BACKGROUND:Medical ozone is a mixture of ozone and oxygen that,in contact with body fluids,rapidly produces reactive oxygen species and activates the body’s antioxidant system.Clinically,the intra-articular injection of medical ozone can effectively alleviate the progress of osteoarthritis.OBJECTIVE:To study the therapeutic effect of intra-articular injection of medical ozone in a rat model of temporomandibular joint osteoarthritis.METHODS:The rat model of temporomandibular joint osteoarthritis was established through intra-articular injection of sodium iodoacetate.Medical ozone with mass concentrations of 20,30 and 40 mg/L was then injected into the joint cavity of the experimental rats once a week for 3 weeks.Model group and control group were injected with the equal amount of saline.The structural changes of the temporomandibular joint were evaluated by cone beam CT examination 1 week after the last injection.The tumor necrosis factorαlevel in the condylar cartilage and plasma was measured by ELISA,and the tissue samples of the temporomandibular joint on the other side were stained with hematoxylin-eosin and safranin O-fast green,and histopathological changes of the temporomandibular joint were evaluated by the modified Mankin’s score.RESULTS AND CONCLUSION:Cone beam CT results indicated that the temporomandibular joint and condylar process of control rats had regular shape and smooth surface,while condylar process deformation and surface defects of rats in the medical ozone 20 and 30 mg/L groups were smaller than those in the model and medical ozone 40 mg/L groups.ELISA results revealed that the expression levels of tumor necrosis factorαin the cartilage and plasma of the rat condylar process were significantly increased in the model group and medical ozone 20,30,40 mg/L groups compared with the control group(P<0.05).Compared with the model group and medical ozone 40 mg/L group,the expression level of tumor necrosis factorαin the cartilage and plasma were significantly decreased in the medical ozone 20,30 mg/L groups(P<0.05).Histological observation revealed that the modified Mankin’s score in the medical ozone 20,30,40 mg/L groups and the model group were significantly higher than that in the control group(P<0.05);the modified Mankin’s score in the medical ozone 20,30 mg/L groups was significantly lower than that in the model group and the medical ozone 40 mg/L group(P<0.05).To conclude,the intraarticular injection of 20 and 30 mg/L medical ozone can significantly delay the progression of osteoarthritis in the temporomandibular joint of rats,but when the mass concentration of ozone is increased to 40 mg/L,it will aggravate osteoarthritis in the temporomandibular joint of rats.