设为首页 加入收藏 登录旧版
O3抑制Notch信号通路减少OA大鼠软骨细胞凋亡的实验研究
An experimental study on the reduction of chondrocyte apoptosis in OA rats by inhibiting the Notch signaling pathway with O3
投稿时间:2022-02-23  修订日期:2022-06-24
DOI:10.3969/j.issn.1672-5972.2022.05.010
中文关键词:  骨关节炎  软骨  Notch信号通路  臭氧
英文关键词:Osteoarthritis  Notch signaling  Ozone  Apoptosis
基金项目:湖北省自然科学基金项目(2020CFB622);中央高校基本科研业务费专项资金资助(2017KFYXJJ076)
作者单位邮编
姚弘毅* 华中科技大学同济医学院附属梨园医院湖北 武汉430077 430077
李燕霞 华中科技大学同济医学院附属梨园医院湖北 武汉430077 430077
梅其杰 广西中医药大学第一附属医院广西 南宁530023 530023
曹静 华中科技大学同济医学院附属梨园医院湖北 武汉430077 430077
杨健 华中科技大学同济医学院附属梨园医院湖北 武汉430077 430077
王琳* 华中科技大学同济医学院附属梨园医院湖北 武汉430077 430077
摘要点击次数: 247
全文下载次数: 171
中文摘要:
      目的 观察大鼠骨关节炎(OA)软骨细胞中Notch信号通路相关因子(Notch-1、Jagged1、keratin1、involucrin)及凋亡生物标志物(caspase-3、Bax、Bcl-2)的表达情况,探索臭氧(O3)作用于OA的具体机制。方法 选取SD大鼠24只,按随机数字表分为空白组、模型组、模型+O3治疗组,每组8只。使用木瓜蛋白酶合半胱氨酸混合液关节腔注射法复制OA模型(右膝),造模成功后,每周在模型+O3治疗组大鼠右膝关节腔内注入2 mL O3(25 μg/mL)1次,模型组注入等体积空气,空白组不做处理;治疗4周后处死大鼠,收集膝OA关节软骨组织,行HE染色观察软骨组织,免疫荧光检测caspase-3、Notch-1表达情况,Western Blot检测Notch-1、Jagged1、Bcl-2、keratin1、involucrin的表达情况。结果 HE染色观察显示,模型+O3治疗组能有效改变软骨退变,使软骨细胞成簇增生,潮线间断。免疫组化及Western Blot检测显示,与空白组相比,caspase-3、Notch-1、Jagged1和Bax蛋白含量在模型组中显著增高(P<0.05);模型+O3治疗组与模型组比较,上述蛋白含量均有所下降,其中caspase-3和Notch-1蛋白含量与模型组相比下降程度更显著,差异有统计学意义(P<0.05);而Bcl-2、keratin1和involucrin蛋白含量在模型组显著降低(P<0.05),经O3治疗后上述蛋白含量显著增高(P<0.05)。结论 Notch信号通路通过调控OA软骨细胞凋亡参与OA发生发展的过程,而O3能通过抑制Notch信号通路减少软骨细胞凋亡,保护关节软骨,延缓OA进展。
英文摘要:
      Objective To explore the specific mechanism of O3 acting on osteoarthritis (OA) by observing the expression of Notch signaling pathway-related factors (Notch-1, Jagged1, keratin1, involucrin) and apoptosis biomarkers (caspase-3, Bax, Bcl-2) in rat OA chondrocytes.Methods Twenty-four SD rats were selected and divided into blank group, model group and model+O3 treatment group randomly(8 rats in each group) before the reproduction of OA model (right knee) by intraarticular injection of papain-cysteine ​​mixture. Every week after the successful modeling, 2 mL of O3 (25 μg/mL) was injected into the right knee joint cavity of the rats in the model+O3 treatment group, the model group was injected with an equal volume of air, and the blank group was not treated. After 4 weeks of treatment, the rats were sacrificed and the knee OA articular cartilage tissue was collected and observed by HE staining. The expression of caspase-3 and Notch-1 was detected by immunofluorescence and the expression of Notch-1, Jagged1, Bcl-2, keratin1, and keratin1 were detected by Western Blot.Results HE staining revealed that the model+O3 treatment group could effectively change the cartilage degeneration, make the chondrocytes proliferate in clusters and the tide line interrupted. Immunohistochemistry and Western Blot detection showed that, compared with the blank group, caspase-3, Notch-1, Jagged1 and the protein contents of Bax were significantly increased in the model group (P<0.05). Compared with the model group, the contents of the above proteins were decreased in the model+O3 treatment group, among which caspase-3 and the protein contents of Notch-1 decreased more substantially compared with the model group, which means the difference was statistically significant (P<0.05); Bcl-2, keratin1 and the protein contents of involucrin were greatly decreased in the model group (P<0.05), and the above protein contents were dramatically increased after O3 treatment (P<0.05).Conclusion The Notch signaling pathway participates in the development of OA by regulating the apoptosis of OA chondrocytes while O3 can reduce chondrocyte apoptosis by inhibiting the Notch signaling pathway and consequently protect articular cartilage, and delay the progression of OA.
查看全文  查看/发表评论  下载PDF阅读器
扫码关注
《生物骨科材料与临床研究》微信公众号