中国组织工程研究 ›› 2018, Vol. 22 ›› Issue (36): 5816-5820.doi: 10.3969/j.issn.2095-4344.0617

• 组织构建实验造模 experimental modeling in tissue construction • 上一篇    下一篇

豨莶草水提取物对痛风性关节炎大鼠JNK信号通路影响

郑春雨1,于雪峰2,陈水林2,徐轶尔3,韩忠丽4,孙贵才2   

  1. (1黑龙江中医药大学,黑龙江省哈尔滨市   150036;2南昌大学第四附属医院,江西省南昌市   330003;3哈药集团药物研究院,黑龙江省哈尔滨市  150025;4哈尔滨医科大学附属第二医院,黑龙江省哈尔滨市   150086)
  • 收稿日期:2018-07-22 出版日期:2018-12-28 发布日期:2018-12-28
  • 通讯作者: 孙贵才,博士,主任医师,南昌大学第四附属医院,江西省南昌市 330003
  • 作者简介:郑春雨,男,1988年生,黑龙江省齐齐哈尔市人,汉族,2015年黑龙江中医药大学毕业,硕士,主要从事骨关节损伤研究。
  • 基金资助:

    国家自然科学基金(81360553)

Effects of aqueous extract of Sigesbeckia orientalis on JNK signaling pathway in rats with gouty arthritis

Zheng Chunyu1, Yu Xuefeng2, Chen Shuilin2, Xu Yier3, Han Zhongli4, Sun Guicai2   

  1. (1Heilongjiang University of Chinese Medicine, Harbin 150036, Heilongjiang Province, China; 2the Fourth Affiliated Hospital of Nanchang University, Nanchang 330003, Jiangxi Province, China; 3Pharmaceutical Academy of Harbin Pharmaceutical Group, Harbin 150025, Heilongjiang Province, China; 4the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, Heilongjiang Province, China)
  • Received:2018-07-22 Online:2018-12-28 Published:2018-12-28
  • Contact: Sun Guicai, MD, Chief physician, the Fourth Affiliated Hospital of Nanchang University, Nanchang 330003, Jiangxi Province, China
  • About author:Zheng Chunyu, Master, Heilongjiang University of Chinese Medicine, Harbin 150036, Heilongjiang Province, China
  • Supported by:

    the National Natural Science Foundation of China, No. 81360553

摘要:

文章快速阅读:

文题释义:
豨莶草:为菊科植物,味辛、苦、寒,具有祛风湿、利关节和解毒之功效,主要用于治疗风湿痹症,关节疼痛,筋骨无力,腰膝酸软等。研究发现豨莶草能够抑制白细胞介素1β活性,降低白细胞介素1β和白细胞介素6水平、抑制一氧化氮 和肿瘤坏死因子α的释放,抑制局部组织炎症,减轻关节炎症反应,从而具有改善痛风性关节炎症状。
JNK信号通路:JNK 信号通路是MAPK 家族的重要成员之一,在细胞受到胁迫性刺激而发生凋亡的过程中发挥重要作用。JNK 位于胞质内,一旦被激活迅速转位入胞核,激活活化转录因子c-Jun、AP-1、JunB、JunD、ATF-2、ELK-1 等的转录活性,活化的转录因子与顺式作用元件相结合,引起大量与凋亡有关的基因表达,同时与炎症的发生有非常重要的关系。
摘要
背景
:现代药理研究表明豨签草主要含有豨签甙、生物碱、皂甙等有效成分,有明确的抗炎、镇痛、改善微循环作用,能有效控制急性痛风的炎症改变。
目的:研究豨莶草水提取物对痛风性关节炎大鼠JNK信号通路影响。
方法:将24只SD大鼠随机分为对照组、模型组和豨莶草组。对照组和模型组灌胃给予生理盐水,连续7 d,豨莶草组灌胃给予2 g/kg的豨莶草水提取物,连续7 d,第7天给药1 h后向模型组和豨莶草组大鼠膝关节腔注射尿酸钠建立痛风性关节炎模型,对照组给予同体积的生理盐水。采用苏木精-伊红染色观察大鼠膝关节滑膜组织病理情况,ELISA检测大鼠血清中白细胞介素β、白细胞介素8和肿瘤坏死因子α水平,Western bloting测定大鼠膝关节滑膜组织中JNK和p-JNK蛋白表达,RT-PCR测定大鼠膝关节滑膜组织中c-jun和AP-1 mRNA表达。
结果与结论:①与对照组比较,模型组膝关节滑膜组织中炎性细胞浸润,滑膜细胞增生,成纤维细胞及小血管增生,豨莶草组膝关节滑膜组织中炎性细胞浸润明显减少,滑膜细胞增生和成纤维细胞增生明显减轻;②模型组大鼠血清中白细胞介素1β、白细胞介素8和肿瘤坏死因子α质量浓度明显增高,豨莶草组血清中白细胞介素1β、白细胞介素8和肿瘤坏死因子α质量浓度明显降低;③模型组滑膜组织中JNK和p-JNK蛋白表达明显增加,AP-1和c-jun mRNA表达明显增加,豨莶草组能够明显降低痛风性关节炎大鼠JNK和p-JNK蛋白及c-jun和 AP-1 mRNA表达;④结果表明,痛风性关节炎能够诱导JNK信号通路异常激活,豨莶草水提物能够明显改善痛风性关节炎症状,并且明显改善JNK信号通路异常激活。

中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松组织工程
ORCID: 0000-0002-1515-9378(孙贵才)

关键词: 痛风性关节炎, 滑膜组织, 豨莶草, MAPK, JNK, 组织构建

Abstract:

BACKGROUND: Sigesbeckia orientalis containing kirenol,  alkaloid and saponins exhibits anti-inflammatory and analgesic properties, improves microcirculation, and effectively controls the inflammatory response in acute gout.
OBJECTIVE: To explore the effect of aqueous extract of Sigesbeckia orientalis on JNK signaling pathway in rats with gouty arthritis.
METHODS: Twenty-four Sprague-Dawley rats were randomly divided into control, model and experimental groups (n=8 per group). Animals in the control and model groups were administrated with normal saline and those in the experimental group were treated with aqueous extract of Sigesbeckia orientalis (2 g/kg) via gavage for 7 days. On day 7, sodiate urate was injected into the knee articular cavity of rats in the model and experimental groups at 1 hour after administration to establish the gouty arthritis models. The control group was given the same volume of normal saline. The pathological changes of synovial tissue were observed by hematoxylin-eosin staining.The serum levels of tumor necrosis factor-α, interleukin-8 and -1β were detected by ELISA. The protein levels of JNK and p-JNK in the synovial tissue were determined by western blot assay. The mRNA expression levels of c-jun, AP-1 were tested by RT-PCR.
RESULTS AND CONCLUSION: Compared with the control group, in the model group, there were inflammatory cell infiltration, synovial cell, fibroblast and small vessel hyperplasia in the synovial tissue. There was an overt decrease in the inflammatory cell infiltration, synovial cell, and fibroblast hyperplasia in the experimental group. The serum levels of tumor necrosis factor-α, interleukin-8 and -1β in the model group were significantly increased, but they were significantly reduced in the experimental group. A significant increase in the protein levels of JNK and p-JNK, and the mRNA expression levels of c-jun, AP-1 in the synovial tissue were found in the model group, which was reversed in the experimental group. These results suggest that the occurrence of gouty arthritis is related to the abnormal activation of JNK signaling pathway, and Sigesbeckia orientalis can significantly improve the symptoms of gouty arthritis via inhibiting JNK signaling pathway.

中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松组织工程

Key words: Arthritis, Synovial Membrane, Drugs, Chinese Herbal, Signal Transduction, Tissue Engineering

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