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右归丸经IL-6/STAT3信号通路对膝骨关节炎模型大鼠软骨组织退变的调控机制
引用本文:颜春鲁,安方玉,刘永琦,王继龙,赵磊,夏鹏飞,周婷,石国秀,赵文坤,杨晓蓉.右归丸经IL-6/STAT3信号通路对膝骨关节炎模型大鼠软骨组织退变的调控机制[J].中国实验方剂学杂志,2020,26(1):17-23.
作者姓名:颜春鲁  安方玉  刘永琦  王继龙  赵磊  夏鹏飞  周婷  石国秀  赵文坤  杨晓蓉
作者单位:甘肃中医药大学 甘肃省高校重大疾病分子医学与中医药防治研究重点实验室, 甘肃省高校中(藏)药化学与质量研究省级重点实验室, 敦煌医学与转化教育部重点实验室, 兰州 730000,甘肃中医药大学 甘肃省高校重大疾病分子医学与中医药防治研究重点实验室, 甘肃省高校中(藏)药化学与质量研究省级重点实验室, 敦煌医学与转化教育部重点实验室, 兰州 730000,甘肃中医药大学 甘肃省高校重大疾病分子医学与中医药防治研究重点实验室, 甘肃省高校中(藏)药化学与质量研究省级重点实验室, 敦煌医学与转化教育部重点实验室, 兰州 730000,甘肃中医药大学 甘肃省高校重大疾病分子医学与中医药防治研究重点实验室, 甘肃省高校中(藏)药化学与质量研究省级重点实验室, 敦煌医学与转化教育部重点实验室, 兰州 730000,甘肃中医药大学 甘肃省高校重大疾病分子医学与中医药防治研究重点实验室, 甘肃省高校中(藏)药化学与质量研究省级重点实验室, 敦煌医学与转化教育部重点实验室, 兰州 730000,甘肃中医药大学 甘肃省高校重大疾病分子医学与中医药防治研究重点实验室, 甘肃省高校中(藏)药化学与质量研究省级重点实验室, 敦煌医学与转化教育部重点实验室, 兰州 730000,甘肃中医药大学 甘肃省高校重大疾病分子医学与中医药防治研究重点实验室, 甘肃省高校中(藏)药化学与质量研究省级重点实验室, 敦煌医学与转化教育部重点实验室, 兰州 730000,甘肃中医药大学 甘肃省高校重大疾病分子医学与中医药防治研究重点实验室, 甘肃省高校中(藏)药化学与质量研究省级重点实验室, 敦煌医学与转化教育部重点实验室, 兰州 730000,甘肃中医药大学 甘肃省高校重大疾病分子医学与中医药防治研究重点实验室, 甘肃省高校中(藏)药化学与质量研究省级重点实验室, 敦煌医学与转化教育部重点实验室, 兰州 730000,甘肃中医药大学 甘肃省高校重大疾病分子医学与中医药防治研究重点实验室, 甘肃省高校中(藏)药化学与质量研究省级重点实验室, 敦煌医学与转化教育部重点实验室, 兰州 730000
基金项目:甘肃省高等学校科研项目(2018A-043);甘肃省中医药管理局科研项目(GZK-2017-2);敦煌医学与转化省部共建教育部重点实验室开放基金项目(DHYX17-10);甘肃省高校中(藏)药化学与质量研究省级重点实验室开放基金项目(zzy-2018-01);甘肃省高校重大疾病分子医学与中医药防治研究重点实验室开放基金项目(FZYX17-18-11)
摘    要:目的:观察右归丸对膝骨关节炎(KOA)模型鼠软骨组织信号转导和转录激活因子3(STAT3)和白细胞介素-6(IL-6)表达水平的影响。方法:将大鼠随机分为假手术组、模型组、硫酸氨基葡萄糖组、右归丸高、中、低剂量组,每组10只。采用改良Hulth法制备大鼠KOA模型,假手术组和模型组给予等体积生理盐水灌胃,右归丸高、中、低剂量组分别给予右归丸4.8,2.4,1.2 g·kg^-1灌胃,硫酸氨基葡萄糖组给予硫酸氨基葡萄糖0.17 g·kg^-1灌胃,连续给药8周。干预结束24 h后股动脉采血处死各组大鼠,取鼠膝关节软骨,采用苏木素-伊红(HE)染色法观察各组软骨的病理改变,并进行Mankin评分;免疫组化法检测各组关节软骨组织中STAT3,超氧化物歧化酶3(SOD3)和Wnt抑制因子1(WIF1)的表达;实时荧光定量聚合酶链式反应(Real-time PCR)检测软骨组织中IL-6 mRNA的表达;蛋白免疫印迹法(Western blot)检测各组关节软骨组中WIF1蛋白的表达。结果:与假手术组比较,模型组大鼠软骨组织Makin评分明显升高,软骨组织STAT3在蛋白水平上的表达明显增加和IL-6 mRNA水平上的表达显著增加,WIF1在蛋白水平上的表达显著降低(P<0.01);模型组关节软骨边缘严重破坏,软骨细胞排列紊乱。与模型组比较,右归丸高剂量干预组大鼠软骨组织Makin评分,STAT3的在蛋白水平上的表达明显降低,右归丸各干预组IL-6 mRNA水平上的表达显著降低,WIF1在蛋白水平上的表达显著增加(P<0.05,P<0.01),软骨结构趋于正常,软骨细胞分布仅偶见不均,关节软骨表面欠光滑。结论:右归丸能显著改善KOA大鼠的关节软骨退变,抑制KOA中软骨组织的炎症反应,这可能与其抑制STAT3和IL-6的表达有关。

关 键 词:膝骨关节炎  右归丸  白细胞介素-6(IL-6)/信号转导和转录激活因子3(STAT3)信号通路  炎症因子
收稿时间:2019/5/22 0:00:00

Regulatory Mechanism of Youguiwan on Articular Cartilage Degeneration via IL-6/STAT3 Signaling Pathway in Rats with Knee Osteoarthritis
YAN Chun-lu,AN Fang-yu,LIU Yong-qi,WANG Ji-long,ZHAO Lei,XIA Peng-fei,ZHOU Ting,SHI Guo-xiu,ZHAO Wen-kun and YANG Xiao-rong.Regulatory Mechanism of Youguiwan on Articular Cartilage Degeneration via IL-6/STAT3 Signaling Pathway in Rats with Knee Osteoarthritis[J].China Journal of Experimental Traditional Medical Formulae,2020,26(1):17-23.
Authors:YAN Chun-lu  AN Fang-yu  LIU Yong-qi  WANG Ji-long  ZHAO Lei  XIA Peng-fei  ZHOU Ting  SHI Guo-xiu  ZHAO Wen-kun and YANG Xiao-rong
Affiliation:Provincial-Level Key Laboratory for Molecular Medicine of Major Diseases and Study on Prevention and Treatment of Traditional Chinese Medicine, Key Laboratory of Medicinal Chemistry and Quality Research for Colleges of Gansu Province, Key Laboratory of Dunhuang Medicine under Ministry of Education, Gansu University of Chinese Medicine, Lanzhou 730000, China,Provincial-Level Key Laboratory for Molecular Medicine of Major Diseases and Study on Prevention and Treatment of Traditional Chinese Medicine, Key Laboratory of Medicinal Chemistry and Quality Research for Colleges of Gansu Province, Key Laboratory of Dunhuang Medicine under Ministry of Education, Gansu University of Chinese Medicine, Lanzhou 730000, China,Provincial-Level Key Laboratory for Molecular Medicine of Major Diseases and Study on Prevention and Treatment of Traditional Chinese Medicine, Key Laboratory of Medicinal Chemistry and Quality Research for Colleges of Gansu Province, Key Laboratory of Dunhuang Medicine under Ministry of Education, Gansu University of Chinese Medicine, Lanzhou 730000, China,Provincial-Level Key Laboratory for Molecular Medicine of Major Diseases and Study on Prevention and Treatment of Traditional Chinese Medicine, Key Laboratory of Medicinal Chemistry and Quality Research for Colleges of Gansu Province, Key Laboratory of Dunhuang Medicine under Ministry of Education, Gansu University of Chinese Medicine, Lanzhou 730000, China,Provincial-Level Key Laboratory for Molecular Medicine of Major Diseases and Study on Prevention and Treatment of Traditional Chinese Medicine, Key Laboratory of Medicinal Chemistry and Quality Research for Colleges of Gansu Province, Key Laboratory of Dunhuang Medicine under Ministry of Education, Gansu University of Chinese Medicine, Lanzhou 730000, China,Provincial-Level Key Laboratory for Molecular Medicine of Major Diseases and Study on Prevention and Treatment of Traditional Chinese Medicine, Key Laboratory of Medicinal Chemistry and Quality Research for Colleges of Gansu Province, Key Laboratory of Dunhuang Medicine under Ministry of Education, Gansu University of Chinese Medicine, Lanzhou 730000, China,Provincial-Level Key Laboratory for Molecular Medicine of Major Diseases and Study on Prevention and Treatment of Traditional Chinese Medicine, Key Laboratory of Medicinal Chemistry and Quality Research for Colleges of Gansu Province, Key Laboratory of Dunhuang Medicine under Ministry of Education, Gansu University of Chinese Medicine, Lanzhou 730000, China,Provincial-Level Key Laboratory for Molecular Medicine of Major Diseases and Study on Prevention and Treatment of Traditional Chinese Medicine, Key Laboratory of Medicinal Chemistry and Quality Research for Colleges of Gansu Province, Key Laboratory of Dunhuang Medicine under Ministry of Education, Gansu University of Chinese Medicine, Lanzhou 730000, China,Provincial-Level Key Laboratory for Molecular Medicine of Major Diseases and Study on Prevention and Treatment of Traditional Chinese Medicine, Key Laboratory of Medicinal Chemistry and Quality Research for Colleges of Gansu Province, Key Laboratory of Dunhuang Medicine under Ministry of Education, Gansu University of Chinese Medicine, Lanzhou 730000, China and Provincial-Level Key Laboratory for Molecular Medicine of Major Diseases and Study on Prevention and Treatment of Traditional Chinese Medicine, Key Laboratory of Medicinal Chemistry and Quality Research for Colleges of Gansu Province, Key Laboratory of Dunhuang Medicine under Ministry of Education, Gansu University of Chinese Medicine, Lanzhou 730000, China
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