文献类型：期刊文献

中文题名：黄芪桂枝五物汤对膝骨关节炎大鼠软骨损伤及NLRP3/Caspase1通路的影响

英文题名：Huangqi Guizhi Wuwu Tang Has Effect on Cartilage Injury and NLRP3/Caspase1 Pathway in Rats with Knee Osteoarthritis

作者：叶秋杰[1];沈海良[1];任国卫[1]

机构：[1]绍兴文理学院附属医院关节外科,浙江绍兴312000

年份：2020

卷号：52

期号：8

起止页码：25

中文期刊名：新中医

外文期刊名：Journal of New Chinese Medicine

语种：中文

中文关键词：膝骨关节炎;软骨损伤;黄芪桂枝五物汤;NLRP3/Caspase1通路;动物实验;大鼠

外文关键词：Knee osteoarthritis;Cartilage injury;Huangqi Guizhi Wuwu tang;NLRP3/Caspase1 pathway;Animal experiment;Rats

中文摘要：目的:探讨黄芪桂枝五物汤对膝骨关节炎(KOA)大鼠软骨损伤及核苷酸结合寡聚化结构域样受体3(NLRP3)/天冬氨酸蛋白水解酶1(Caspase1)通路的影响。方法:将120只SD大鼠随机分成对照组、模型组、美洛昔康组、黄芪桂枝五物汤低、中、高剂量组。除对照组外,其余各组建立KOA软骨损伤模型。模型制备成功后对照组、模型组给予等体积的生理盐水;美洛昔康组给予40.0 mg/kg的美洛昔康溶液;黄芪桂枝五物汤低、中、高剂量组分别按20.0、40.0、80.0 mg/kg的剂量给予黄芪桂枝五物汤。实验结束后,进行大鼠关节炎症积分、KOA软骨Mankin's评分,测定机械痛阈(PWPT)及热刺激潜伏期(PWTL);测定膝关节软骨组织中NLRP3、Caspase1 mRNA及蛋白表达水平,白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)表达水平。结果:与对照组比较,模型组PWPT、PWTL降低(P<0.05);关节炎症积分,Mankin's评分,NLRP3、Caspase1 mRNA及蛋白表达水平,IL-1β、IL-6、TNF-α蛋白表达水平升高(P<0.05)。与模型组比较,美洛昔康组和黄芪桂枝五物汤各剂量组PWPT、PWTL升高(P<0.05);关节炎症积分,Mankin's评分,NLRP3、Caspase1 mRNA及蛋白表达水平,IL-1β、IL-6、TNF-α蛋白表达水平降低(P<0.05),且黄芪桂枝五物汤各剂量组存在明显的剂量-效应关系(P<0.05)。与美洛昔康组比较,黄芪桂枝五物汤低、中剂量组PWPT、PWTL较低(P<0.05);关节炎症积分,Mankin's评分,NLRP3、Caspase 1 mRNA及蛋白表达水平,IL-1β、IL-6、TNF-α蛋白表达水平较高(P<0.05);而黄芪桂枝五物汤高剂量组以上各指标差异无统计学意义(P>0.05)。结论:黄芪桂枝五物汤能减轻KOA软骨损伤程度,其高剂量效果尤为明显;其机制与黄芪桂枝五物汤能降低炎症信号通路NLRP3、Caspase1 mRNA及蛋白的表达,进而抑制炎症因子IL-1β、IL-6、TNF-α的表达有关。

外文摘要：Objective:To investigate the effect of Huangqi Guizhi Wuwu tang on cartilage injury and nucleotide-binding oligomerization domain-like receptor 3(NLRP3)/aspartic acid protease 1(Caspase1) pathway in rats with knee osteoarthritis(KOA). Methods: A total of 120 SD rats were randomly divided into the control group, the model group, the meloxicam group and the Huangqi Guizhi Wuwu tang groups of low-dose,medium-dose and high-dose. Except those in the control group, rat models of cartilage injury in KOA were established in all the other groups. After successful establishment, the control group and the model group were given the same volume of saline;the meloxicam group was given 40.0 mg/kg of meloxicam solution;the Huangqi Guizhi Wuwu tang groups of low-dose,medium-dose and high-dose were respectively given 20.0, 40.0 and 80.0 mg/kg of Huangqi Guizhi Wuwu tang. After experiment, the scores of joint inflammation and Mankin’s scores of cartilage in rats with KOA were performed, and paw withdrawal pressure threshold(PWPT) and paw withdrawal thermal latency(PWTL) were measured;mRNA and protein expression levels of NLRP3 and Caspase1 and the expression levels of interleukin-1β(IL-1β),interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in knee joint cartilage were measured. Results: Compared with those in the control group, the PWPT and PWTL in the model group were decreased(P<0.05);the scores of joint inflammation,Mankin’s scores,mRNA and protein expression levels of NLRP3 and Caspase1,and protein expression levels of IL-1β,IL-6 and TNF-αwere increased(P<0.05). Compared with those in the model group, the PWPT and PWTL in the meloxicam group and the Huangqi Guizhi Wuwu tang groups of all doses were increased(P<0.05);the scores of joint inflammation,Mankin’s scores,mRNA and protein expression levels of NLRP3 and Caspase1,and protein expression levels of IL-1β,IL-6 and TNF-αwere decreased(P<0.05),and there was a significant dose-effect relationship being found in the Huangqi Guizhi Wuwu tang groups of all doses(P<0.05). Compared with those in the meloxicam group,the PWPT and PWTL in the Huangqi Guizhi Wuwu tang groups of low-dose and medium-dose were lower(P<0.05);the scores of joint inflammation, Mankin’s scores, mRNA and protein expression levels of NLRP3 and Caspase1, and protein expression levels of IL-1β, IL-6 and TNF-αwere higher(P<0.05);there was no significant difference being found in the comparison of the above indexes in the Huangqi Guizhi Wuwu tang groups of high-dose(P>0.05). Conclusion:The application of Huangqi Guizhi Wuwu tang can reduce the degree of cartilage injury in KOA,especially in high dose. Its mechanism is related to the fact that Huangqi Guizhi Wuwu tang can reduce the mRNA and protein expression of the inflammatory signaling pathways of NLRP3 and Caspase1 and thus inhibiting the expression of inflammatory factors including IL-1β,IL-6 and TNF-α.