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青牛解毒汤的抗痛风性关节炎作用以及机制的初步研究

A Preliminary Study of the Anti-Gouty Arthritis Effect and Mechanism of Qingniu Jiedu Decoction(青牛解毒汤)
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摘要 目的:观察青牛解毒汤的抗痛风性关节炎作用以及机制的初步研究。方法:通过完全随机设计将60只雄性SD大鼠分为正常对照组、模型对照组、秋水仙碱片5×10^(-3)g/kg组以及青牛解毒汤23.6、47.3、94.5 g/kg组,每组10只。在注射造模0、6、12、24、48 h利用缚绳法测量大鼠踝关节周长,测定肿胀度,同时在24 h后对大鼠步态以及关节炎指数进行评价,造模后48 h腹主动脉取血,利用Luminex多因子检测技术测定血清中白细胞介素-1β(IL-1β)、IL-4、IL-10的含量;HE染色观察大鼠右侧踝关节滑膜病理变化;采用qPCR法检测关节滑膜中Nlrp3、Asc、Caspase-1 mRNA表达;采用免疫组化法检测关节滑膜中NLRP3、ASC、Caspase-1的蛋白表达。结果:与正常对照组比较,模型对照组在造模后6、12、24、48 h的关节肿胀度显著升高,大鼠的步态以及关节炎症评分明显升高(P<0.01),IL-1β含量显著升高,IL-4与IL-10含量明显降低(P<0.05或P<0.01);与模型对照组比较,在造模后6、12、24、48 h,秋水仙碱以及青牛解毒汤23.6、47.3、94.5 g/kg组均能明显抑制大鼠踝关节肿胀度,明显改善24 h的步态级别及关节炎症指数;青牛解毒汤47.3 g/kg组能明显降低IL-1β含量,明显增加IL-10含量(P<0.05),青牛解毒汤23.6 g/kg组能够显著增加IL-4含量(P<0.01),青牛解毒汤各组能够下调Nlrp3、Asc、Caspase1 mRNA和蛋白表达,减少踝关节滑膜组织中炎症细胞的浸润和细胞水肿(P<0.05或P<0.01)。结论:青牛解毒汤具有抗痛风性关节炎作用,其机制可能与调控NLRP3/ASC/Caspase-1通路,降低痛风性关节炎大鼠血清中IL-1β的含量以及增加IL-4、IL-10含量有关。 Objective:To conduct a preliminary study of the anti-gouty arthritis effect and mechanism of Qingniu Jiedu Decoction(青牛解毒汤).Methods:Sixty male SD rats were randomLy divided into the following groups:a normal control group,a model control group,a colchicine group(5×10^(-3) g/kg),and low-,medium-,and high-dose Qingniu Jiedu Decoction groups(23.6,47.3,and 94.5 g/kg),with 10 rats in each group.The ankle joint circumference and swelling degree of rats were measured using the ligature method at 0,6,12,24,and 48 hours after modeling.The gait and arthritis index of rats were evaluated 24 hours after modeling.Blood samples were taken from the abdominal aorta 48 hours after modeling,and the levels of interleukin-1β(IL-1β),IL-4,and IL-10 in the serum were measured using Luminex multiplex assay.Histological changes of the right ankle joint synovium were observed using HE staining.The expression of NLRP3,ASC,and Caspase-1 in the synovium was detected using qPCR,and the protein expression of NLRP3,ASC,and Caspase-1 in the synovium was measured using immunohistochemistry.Results:Compared with the normal control group,the model control group showed a significant increase in joint swelling at 6,12,24,and 48 hours after modeling,elevated gait and arthritis scores of rats(P<0.01),increased levels of IL-1β,and decreased levels of IL-4 and IL-10(P<0.05,P<0.01).Compared with the model control group,colchicine and Qingniu Jiedu Decoction at doses of 23.6,47.3,and 94.5 g/kg significantly inhibited ankle joint swelling and reduced gait and arthritis scores at 6,12,24,and 48 hours after modeling.Qingniu Jiedu Decoction at 47.3 g/kg significantly decreased the level of IL-1β(P<0.05),Qingniu Jiedu Decoction at 23.6 g/kg significantly increased the level of IL-4(P<0.01),and Qingniu Jiedu Decoction at 47.3 g/kg significantly increased the level of IL-10(P<0.05 or P<0.01).Qingniu Jiedu Decoction downregulated the mRNA and protein expression of NLRP3,ASC,and Caspase-1 and reduced the infiltration of inflammatory cells and cell edema in the ankle joint synovium.Conclusion:Qingniu Jiedu Decoction has an anti-gouty arthritis effect,which may be related to the regulation of the NLRP3/ASC/Caspase-1 pathway,the reduction of IL-1βlevel in the serum of gouty arthritis rats,and the increase in IL-4 and IL-10 levels.
作者 覃骊兰 唐周一豆 韦义 黄宝萱 张颖琳 蓝毓营 QIN LiLan;TANG Zhouyidou;WEI Yi;HUANG Baoxuan;ZHANG Yinglin;LAN Yuying(Guangxi University of Chinese Medicine,Nanning 530001)
机构地区 广西中医药大学
出处 《中药药理与临床》 CSCD 北大核心 2023年第12期53-57,共5页 Pharmacology and Clinics of Chinese Materia Medica
基金 广西中医药大学桂派杏林拔尖人才资助项目[桂中医大党(2022)23号](2022C006) 广西壮瑶药重点实验室科研任务(编号:19-050-14) 广西中医药大学2019-2021年广西一流学科建设开放课题(编号:2019XK042)。
关键词 青牛解毒汤 痛风性关节炎 微晶尿酸钠 白介素-1Β 白介素-4 白介素-10 炎症小体 Qingniu Jiedu Decoction(青牛解毒汤) Gouty arthritis MSU IL-1β IL-4 IL-10 Inflammasome
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