[1]姜厚森△ 李忠 韩宁 赵阳 郭佳 吴培刚.新型蛋白酶体抑制剂对骨关节炎的治疗作用及其分子机制研究[J].中国中医骨伤科杂志,2021,29(05):1-5.
　JIANG Housen LI Zhong HAN Ning ZHAO Yang GUO Jia WU Peigang.Therapeutic Efficacy and Molecular Mechanism of a NewProteasome Inhibitor on Osteoarthritis[J].Chinese Journal of Traditional Medical Traumatology & Orthopedics,2021,29(05):1-5.
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新型蛋白酶体抑制剂对骨关节炎的治疗作用及其分子机制研究()
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《中国中医骨伤科杂志》[ISSN:1005-0205/CN:42-1340/R]

卷:
第29卷
期数:
2021年05期
页码:
1-5
栏目:
实验研究
出版日期:
2021-05-15

文章信息/Info

Title:
Therapeutic Efficacy and Molecular Mechanism of a NewProteasome Inhibitor on Osteoarthritis
文章编号:
1005-0205(2021)05-0001-05
作者:
姜厚森1△ 李忠1 韩宁1 赵阳2 郭佳1 吴培刚2
1山东潍坊市人民医院(潍坊医学院第一附属医院)手足骨外科(山东 潍坊,261041)2潍坊医学院
Author(s):
JIANG Housen1△ LI Zhong1 HAN Ning1 ZHAO Yang2 GUO Jia1 WU Peigang2
1Department of Hand,Foot and Orthopedics,Weifang People’s Hospital; The First Affiliated Hospital of Weifang Medical College,Weifang 261041,Shandong China; 2Weifang Medical College,Weifang 261053,Shandong China.
关键词:
新型蛋白酶体抑制剂;  软骨细胞;  基质降解;  骨关节炎
Keywords:
new proteasome inhibitor;  chondrocytes;  matrix degradation;  osteoarthritis
分类号:
R-33
文献标志码:
A
摘要:
目的:探讨新型蛋白酶体抑制剂YSY-01A对骨关节炎(OA)大鼠的治疗作用及其分子机制。方法:体外培养人软骨细胞,分为对照组(NC)、白细胞介素-1β(IL-1β)组、YSY-01A 6.2 μmol/L、12.5 μmol/L、25 μmol/L组。采用一氧化氮(NO)试剂盒测量细胞中上清NO含量; 采用ELISA法检测细胞上清中PGE2、IL-6、TNF-α含量; 蛋白免疫印迹(Western Blot)检测细胞中COX-2和iNOS的蛋白水平。SPF级雄性SD大鼠72只,随机分为假手术组、模型组、YSY-01A低剂量、中剂量、高剂量组和阳性药组。采用前交叉韧带横断术建立骨关节炎大鼠模型,观察软骨病理变化,测量OA大鼠血清中COX-2和PGE2水平及组织中iNOS和NO含量。结果:与IL-1β组比较,YSY-01A 6.2 μmol/L、12.5 μmol/L、25 μmol/L组细胞上清NO、PGE2、IL-6和TNF-α含量明显减少,差异有统计学意义(P<0.05); 细胞中COX-2和iNOS蛋白表达下调,差异有统计学意义(P<0.05)。与模型组比较,YSY-01A中剂量和高剂量组软骨病理变化缓解,血清中COX-2和PGE2含量下降,差异有统计学意义(P<0.05); 组织中iNOS和NO含量减少,差异有统计学意义(P<0.05)。结论:YSY-01A对骨关节具有一定的保护作用,可能与抑制炎症反应和软骨基质降解有关。
Abstract:
To investigate the therapeutic efficacy and molecular mechanism of a new protease inhibitor YSY-01A on osteoarthritis.Methods:Human chondrocytes were cultured in vitro and divided into NC group,IL-1β group,YSY-01A 6.2 μmol/L,12.5 μmol/L,and 25 μmol/L groups.Nitric oxide(NO)kit was used to measure the NO content in the cell supernatant.ELISA was used to measure the PGE2,IL-6,TNF-α content in the cell supernatant.Western Blot was used to detect the protein levels of COX-2 and iNOS in the cells.72 SPF male SD rats were randomly divided into sham group,model group,YSY-01A low-dose,medium-dose,high-dose group and positive drug group.Anterior cruciate ligament transection was used to establish a rat model of osteoarthritis.The pathological changes of cartilage were observed by HE and safranine O-Fast green staining.The COX-2 and PGE2 in serum and the content of iNOS and NO in tissues were detected by ELSIA.Results:Compared with IL-1β group,the levels of NO,PGE2,IL-6 and TNF-α in YSY-01A(6.2 μmol/L,12.5 μmol/L,25 μmol/L)groups were decreased significantly(P<0.05).The expression of COX-2 and iNOS protein was down-regulated in YSY-01A(6.2 μmol/L,12.5 μmol/L,25 μmol/L)groups(P<0.05).Compared with the model group,the pathological changes of cartilage in YSY-01A middle-dose and high-dose groups were alleviated.The content of COX-2 and PGE2 in serum were decreased in YSY-01A middle-dose and high-dose groups(P<0.05).The content of iNOS and NO in tissue were decreased in YSY-01A middle-dose and high-dose groups(P<0.05).Conclusion:YSY-01A has a protective efficacy on osteoarthritis,which may be related to the inhibition of inflammation and cartilage matrix degradation.

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备注/Memo

备注/Memo:
基金项目:山东省医药卫生科技发展计划项目(2016ws0641)
△通信作者 E-mail:jhsresolve81@163.com
更新日期/Last Update: 2021-05-15