[1]李　刚,籍胤玺,侯晓东.盐酸多奈哌齐对骨关节炎大鼠软骨组织中肿瘤坏死因子-α和解整链蛋白金属蛋白酶-5表达的影响[J].新乡医学院学报,2021,38(8):701-705.[doi:10.7683/xxyxyxb.2021.08.001]
　LI Gang,JI Yinxi,HOU Xiaodong.Effect of donepezil hydrochloride on the expression of tumor necrosis factor-α and a disintegrin and metalloproteinase with thrombospondin motifs-5 in cartilage tissues of rats with osteoarthritis[J].Journal of Xinxiang Medical University,2021,38(8):701-705.[doi:10.7683/xxyxyxb.2021.08.001]
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盐酸多奈哌齐对骨关节炎大鼠软骨组织中肿瘤坏死因子-α和解整链蛋白金属蛋白酶-5表达的影响
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《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
38
期数:
2021年8
页码:
701-705
栏目:
基础研究
出版日期:
2021-08-05

文章信息/Info

Title:
Effect of donepezil hydrochloride on the expression of tumor necrosis factor-α and a disintegrin and metalloproteinase with thrombospondin motifs-5 in cartilage tissues of rats with osteoarthritis
作者:
李　刚1; 籍胤玺1; 侯晓东2
（1.南阳市中心医院骨科,河南　南阳　4730002.河南大学第一附属医院骨科,河南　开封　475000）
Author(s):
LI Gang1; JI Yinxi1; HOU Xiaodong2
(1.Department of Orthopaedics,Nanyang Central Hospital，Nanyang 473000,Henan Province,China；2.Department of Orthopaedics,the First Affiliated Hospital of Henan University,Kaifeng 475000,Henan Province,China)
关键词:
骨关节炎; 肿瘤坏死因子-α; 解整链蛋白金属蛋白酶-5; 盐酸多奈哌齐
Keywords:
osteoarthritistumor necrosis factor-αa disintegrin and metalloproteinase with thrombospondin motifs-5donepezil hydrochloride
分类号:
R864.3
DOI:
10.7683/xxyxyxb.2021.08.001
文献标志码:
A
摘要:
目的　探讨盐酸多奈哌齐对骨关节炎大鼠软骨组织中肿瘤坏死因子-α（TNF-α）和带有血小板凝血酶敏感蛋白样模体的解整链蛋白金属蛋白酶-5(ADAMTS-5)表达的影响。方法　将30只无特定病原体级Sprague Dawley雌性大鼠随机分为正常组、模型组和盐酸多奈哌齐组，每组10只。模型组和盐酸多奈哌齐组大鼠膝关节腔注射40 g·L-1木瓜蛋白酶0.15 mL制备膝骨关节炎模型，3 d注射1次，共注射3次；正常组大鼠注射等体积的生理盐水。造模成功后第7天，盐酸多奈哌齐组大鼠给予盐酸多奈哌齐（3 mL·kg-1）灌胃，每日1次；正常组和模型组大鼠给予相同剂量的生理盐水灌胃,每日1次；均持续灌胃6周。3组大鼠分别于灌胃1、3、6周时采用关节炎指数评分评估大鼠关节炎症程度灌胃结束时取大鼠膝关节，采用苏木精-伊红染色观察3组大鼠关节结构改变情况免疫组织化学法检测3组大鼠膝关节软骨组织中TNF-α、ADAMTS-5蛋白表达，反转录聚合酶链反应法检测3组大鼠膝关节软骨组织中TNF-α、ADAMTS-5 mRNA表达，Western blot法检测3组大鼠膝关节软骨组织中TNF-α、ADAMTS-5蛋白表达。结果　灌胃1、3、6周时，模型组和盐酸多奈哌齐组大鼠关节炎指数评分均显著高于正常组（P＜0.05），盐酸多奈哌齐组大鼠关节炎指数评分显著低于模型组（P＜0.05）。正常组大鼠未见滑膜组织炎症细胞浸润、滑膜纤维增生现象；模型组大鼠关节组织内大量炎症细胞浸润，关节囊可见囊性炎症增生，囊内韧带神经损伤，滑膜和纤维组织增生；盐酸多奈哌齐组大鼠滑膜组织炎症细胞浸润减少，纤维增生改善。模型组和盐酸多奈哌齐组大鼠膝关节软骨组织中TNF-α、ADAMTS-5 mRNA和蛋白相对表达量均显著高于正常组（P＜0.05），盐酸多奈哌齐组大鼠膝关节软骨组织中TNF-α、ADAMTS-5 mRNA和蛋白相对表达量均显著低于模型组（P＜0.05）。模型组和盐酸多奈哌齐组大鼠膝关节软骨组织中TNF-α、ADAMTS-5阳性细胞数均显著高于正常组（P＜0.05），盐酸多奈哌齐组大鼠膝关节软骨组织中TNF-α、ADAMTS-5阳性细胞数均显著低于模型组（P＜0.05）。结论　盐酸多奈哌齐可通过抑制软骨组织中TNF-α、ADAMTS-5的表达对骨关节炎大鼠软骨起到保护作用。
Abstract:
Objective　To investigate the effect of donepezil hydrochloride on the expression of tumor necrosis factor-α（TNF-α）and a disintegrin and metalloproteinase with thrombospondin motifs-5(ADAMTS-5) in cartilage tissues of rats with osteoarthritis.Methods　Thirty specific pathogen-free Sprague Dawley female rats were randomly divided into normal group,model group and donepezil hydrochloride group,with 10 rats in each group.Rats in the model group and donepezil hydrochloride group were injected with 40 g·L-1 papain(0.15 mL) into the knee joint cavity to prepare knee osteoarthritis model,once every 3 days for a total of 3 timesthe rats in the normal group were injected with equal volume of saline.On the 7th day after the successful modeling,the rats in the donepezil hydrochloride group were given donepezil hydrochloride (3 mL·kg-1) by gavage,once a daythe rats in the normal group and the model group were given the same dose of normal saline by gavage,once a dayall rats were continued to gavage for 6 weeks.The degree of arthritis of rats in the three groups was evaluated by arthritis index at 1,3 and 6 weeks after intragastric administrationat the and of gavage,the knee joint of rats in the three groups was taken and the changes of joint structure were observed by hematoxylin-eosin staining，the expressions of TNF-α and ADAMTS-5 in cartilage tissues of knee joint of rats in the three groups were detected by immunohistochemistry,the expressions of TNF-α and ADAMTS-5 mRNA in the cartilage tissues of knee joint of rats in the three groups were detected by reverse transcription polymerase chain reaction,the expressions of TNF-α and ADAMTS-5 protein in cartilage tissues of knee joint of rats in the three groups were detected by Western blot.Results　At 1,3 and 6 weeks after intragastric administration,the arthritis index of rats in the model group and donepezil hydrochloride group was significantly higher than that in the normal group (P＜0.05)the arthritis index of rats in the donepezil hydrochloride group was significantly lower than that in the model group (P＜0.05).In the normal group,there was no infiltration of inflammatory cells in synovial tissue and no synovial fiber hyperplasia was found.In the model group,there was a large number of inflammatory cells infiltration in joint tissue and cystic inflammatory hyperplasia could be seen in the joint capsule,intracapsular ligament nerve was injured,and synovial,fibrous tissues proliferated.In the donepezil hydrochloride group,the infiltration of inflammatory cells in synovial tissue decreased and the proliferation of fibers improved.The relative expressions of TNF-α,ADAMTS-5 mRNA and protein in the model group and donepezil hydrochloride group were significantly higher than those in the normal group (P＜0.05)the relative expressions of TNF-α,ADAMTS-5 mRNA and protein in the donepezil hydrochloride group were significantly lower than those in the model group (P＜0.05).The number of TNF-α and ADAMTS-5 positive cells in the model group and the donepezil hydrochloride group was significantly higher than that in the normal group (P＜0.05)the number of TNF-α and ADAMTS-5 positive cells in the donepezil hydrochloride group was significantly lower than that in the model group (P＜0.05).Conclusion　Donepezil hydrochloride can protect the cartilage tissue of osteoarthritis rats by inhibiting the expression of TNF-α and ADAMTS-5.

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更新日期/Last Update: 2021-08-05