[1]张华燕,何援军.薯蓣皂苷元改善类风湿关节炎模型大鼠关节肿胀的效果及作用机制研究[J].中医正骨,2021,33(04):44-50.
 ZHANG Huayan,HE Yuanjun.Efficacy and mechanism of diosgenin against joint swelling in rat models with rheumatoid arthritis[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2021,33(04):44-50.
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薯蓣皂苷元改善类风湿关节炎模型大鼠关节肿胀的效果及作用机制研究()
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《中医正骨》[ISSN:1001-6015/CN:41-1162/R]

卷:
第33卷
期数:
2021年04期
页码:
44-50
栏目:
基础研究
出版日期:
2021-04-20

文章信息/Info

Title:
Efficacy and mechanism of diosgenin against joint swelling in rat models with rheumatoid arthritis
作者:
张华燕何援军
(浙江衢化医院,浙江 衢州 324004)
Author(s):
ZHANG HuayanHE Yuanjun
Zhejiang Quhua Hospital,Quzhou 324004,Zhejiang,China
关键词:
关节炎类风湿 薯蓣皂苷元 Nod样受体蛋白3炎性体 动物实验 大鼠Sprague-Dawley
Keywords:
arthritisrheumatoid diosgenin Nod-like receptor protein 3 inflammasome animal experimentation rats Sprague-Dawley
摘要:
目的:探讨薯蓣皂苷元改善类风湿关节炎(rheumatoid arthritis,RA)模型大鼠关节肿胀的效果及可能的作用机制。方法:从70只6周龄SPF级雄性SD大鼠中随机选取55只,建立Ⅱ型胶原诱导的RA大鼠模型,剩余15只纳入空白组。将造模成功的48只大鼠随机分为模型组、激活剂组和薯蓣皂苷元组,每组各16只。薯蓣皂苷元组以薯蓣皂苷元干预,激活剂组以尼日利亚菌素钠盐干预,空白组、模型组仅给予生理盐水。每天干预1次,共干预2周。干预结束后,采用关节炎指数评定各组大鼠的关节肿胀情况,检测外周血炎症因子[白细胞介素(interleukin,IL)-1β、IL-6、肿瘤坏死因子(tumor necrosis factor-α,TNF-α)]和氧化应激因子[丙二醛(malondialdehyde,MDA)、超氧化物歧化酶(superoxide dismutase,SOD)、谷胱甘肽(glutathione,GSH)]含量,取大鼠关节滑膜组织HE染色后进行病理学观察,并测定大鼠滑膜组织中Nod样受体蛋白3(Nod-like receptor protein 3,NLRP3)炎性体信号通路相关蛋白[IL-1β、半胱氨酸天冬氨酸蛋白酶1(Caspase-1)及NLRP3]含量。结果:①关节肿胀情况。模型组、激活剂组及薯蓣皂苷元组大鼠的关节炎指数比较,差异有统计学意义[(3.43±0.32)分,(2.44±0.20)分,(0.86±0.10)分,F=14.974,P=0.000]。激活剂组和薯蓣皂苷元组的关节炎指数均低于模型组(P=0.001,P=0.000),薯蓣皂苷元组的关节炎指数低于激活剂组(P=0.000)。②外周血炎症因子含量。空白组、模型组、激活剂组及薯蓣皂苷元组大鼠的血清IL-1β、IL-6、TNF-α含量比较,组间差异均有统计学意义[IL-1β:(128.82±13.71)μg·mL-1,(279.44±28.21)μg·mL-1,(213.12±20.65)μg·mL-1,(176.76±19.25)μg·mL-1,F=36.554,P=0.000; IL-6:(119.56±12.42)μg·mL-1,(271.18±27.11)μg·mL-1,(198.43±21.36)μg·mL-1,(146.85±15.72)μg·mL-1,F=28.643,P=0.000; TNF-α:(203.63±22.08)μg·mL-1,(328.91±36.22)μg·mL-1,(275.88±27.52)μg·mL-1,(237.89±23.12)μg·mL-1,F=41.832,P=0.000]。模型组、激活剂组及薯蓣皂苷元组的血清IL-1β、IL-6、TNF-α含量均高于空白组(IL-1β:P=0.001,P=0.000,P=0.002; IL-6:P=0.001,P=0.000,P=0.016; TNF-α:P=0.000,P=0.002,P=0.043); 激活剂组和薯蓣皂苷元组的血清IL-1β、IL-6、TNF-α含量均低于模型组(IL-1β:P=0.003,P=0.000; IL-6:P=0.002,P=0.000; TNF-α:P=0.031,P=0.001); 薯蓣皂苷元组的血清IL-1β、IL-6、TNF-α含量均低于激活剂组(P=0.021,P=0.002,P=0.046)。③外周血氧化应激因子含量。空白组、模型组、激活剂组及薯蓣皂苷元组大鼠的血浆MDA、SOD、GSH含量比较,组间差异均有统计学意义[MDA:(10.24±1.87)μmol·L-1,(36.51±3.63)μmol·L-1,(21.33±2.42)μmol·L-1,(16.37±1.85)μmol·L-1,F=15.632,P=0.000; SOD:(145.52±14.72)U·mL-1,(40.41±6.96)U·mL-1,(79.42±8.32)U·mL-1,(106.12±10.22)U·mL-1,F=21.334,P=0.000; GSH:(38.54±3.82)U·mL-1,(14.77±2.12)U·mL-1,(21.63±2.19)U·mL-1,(28.63±2.97)U·mL-1,F=13.213,P=0.000]。模型组、激活剂组及薯蓣皂苷元组的血浆MDA含量均高于空白组(P=0.000,P=0.000,P=0.001),血浆SOD、GSH含量均低于空白组(SOD:P=0.000,P=0.000,P=0.001; GSH:P=0.000,P=0.000,P=0.002); 激活剂组及薯蓣皂苷元组的血浆MDA含量均低于模型组(P=0.000,P=0.000),血浆SOD、GSH含量均高于模型组(SOD:P=0.000,P=0.000; GSH:P=0.001,P=0.000); 激活剂组的血浆MDA含量高于薯蓣皂苷元组(P=0.007),血浆SOD、GSH含量均低于薯蓣皂苷元组(P=0.002,P=0.003)。④滑膜组织病理学观察结果。空白组关节滑膜组织结构、形态正常; 模型组关节滑膜组织有炎性细胞浸润,滑膜细胞增生,血管扩张,形成血栓; 激活剂组关节滑膜组织病理变化较模型组改善,但有轻微滑膜细胞增生; 薯蓣皂苷元组关节滑膜组织病理变化明显改善。⑤滑膜组织NLRP3炎性体信号通路相关蛋白含量。空白组、模型组、激活剂组及薯蓣皂苷元组大鼠关节滑膜组织IL-1β、Caspase-1、NLRP3含量比较,组间差异均有统计学意义(IL-1β:0.46±0.07,1.02±0.10,0.72±0.08,0.56±0.06,F=31.025,P=0.000; Caspase-1:0.54±0.08,1.16±0.12,0.90±0.10,0.73±0.08,F=23.658,P=0.000; NLRP3:0.69±0.08,1.27±0.12,1.01±0.11,0.88±0.09,F=28.754,P=0.000); 模型组、激活剂组及薯蓣皂苷元组滑膜组织IL-1β、Caspase-1、NLRP3含量均高于空白组(IL-1β:P=0.000,P=0.001,P=0.042; Caspase-1:P=0.000,P=0.000,P=0.006; -----------------------------------------------
Abstract:
To explore the efficacy of diosgenin against joint swelling in rat models with rheumatoid arthritis(RA)and its possible mechanism.Methods:From the 70 6-week-old SPF-grade male Sprague-Dawley(SD)rats,55 rats were randomly selected and intracutaneously injected with typeⅡcollagen for inducing RA,and the remaining 15 rats were classified into blank group.The successfully modeled 48 rats were then randomly assigned to model group,activator group and diosgenin group,16 rats in each group.The rats in diosgenin group were treated with diosgenin,the ones in activator group with nigericin sodium salt,and the ones in blank group and model group with normal saline(NS),once a day for consecutive two weeks.After the end of intervention,the joint swelling of rats in each group was evaluated based on the arthritis index(AI).The levels of inflammatory cytokines including interleukin(IL)-1β,IL-6 and tumor necrosis factor-α(TNF-α)and oxidative stress(OS)inducers including malondialdehyde(MDA),superoxide dismutase(SOD)and glutathione(GSH)in peripheral blood were detected.The synovial tissues of rat joints were stained with hematoxylin-eosin(HE)for pathological observation,followed by the determination of the expression levels of related proteins including IL-1β,cysteinyl aspartate-specific protease-1(Caspase-1)and Nod-like receptor protein 3(NLRP3)in the NLRP3 inflammasome signaling pathway.Results:The difference in AI scores among model group,activator group and diosgenin group was statistically significant(3.43±0.32,2.44±0.20,0.86±0.10 points,F=14.974,P=0.000).The AI scores of activator group and diosgenin group were lower than that of model group(P=0.001,P=0.000),and that in diosgenin group was even lower(P=0.000).The comparison of serum IL-1β,IL-6 and TNF-α levels of rats among blank group,model group,activator group and diosgenin group revealed significant differences(IL-1β:128.82±13.71,279.44±28.21,213.12±20.65,176.76±19.25 μg/mL,F=36.554,P=0.000; IL-6:119.56±12.42,271.18±27.11,198.43±21.36,146.85±15.72 μg/mL,F=28.643,P=0.000; TNF-α:203.63±22.08,328.91±36.22,275.88±27.52,237.89±23.12 μg/mL,F=41.832, P=0.000).The serum IL-1β,IL-6 and TNF-α levels in model group,activator group and diosgenin group were all higher than those in blank group(IL-1β:P=0.001,P=0.000,P=0.002; IL-6:P=0.001,P=0.000,P=0.016; TNF-α:P=0.000,P=0.002,P=0.043)...

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备注/Memo:
基金项目:2018年度衢州市科技计划指导性项目(第二批)(2018127)
通讯作者:张华燕 E-mail:Dsbz1122@163.com
更新日期/Last Update: 1900-01-01