藏药麻花秦艽醇提物对胶原诱导型关节炎模型小鼠滑膜组织中NF-κB p65表达的影响
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篇名: 藏药麻花秦艽醇提物对胶原诱导型关节炎模型小鼠滑膜组织中NF-κB p65表达的影响
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摘要: 目的:考察藏药麻花秦艽醇提物(GSM)对胶原诱导型关节炎(CIA)模型小鼠滑膜组织中核转录因子κB p65(NF-κB p65)表达的影响,为阐明其抗类风湿关节炎(RA)的作用机制提供参考。方法:将40只小鼠随机分为正常组、模型组、地塞米松组(阳性对照,0.25 mg/kg)和GSM低、高剂量组(25、50 mg/kg,以生药量计),每组8只。除正常组外,其余各组小鼠均于尾根部多点皮内注射鸡Ⅱ型胶原制备CIA模型。自造模当日起,给药组小鼠每天灌胃相应药物1次,正常组和模型组小鼠灌胃等量生理盐水,连续给药28 d。给药后7、14、21、28、35 d,测定各组小鼠的关节炎指数(AI);给药结束后,测定各组小鼠的脾指数和胸腺指数,采用酶联免疫吸附法检测小鼠血清中白细胞介素1β(IL-1β)、IL-6和肿瘤坏死因子α(TNF-α)水平,苏木精-伊红染色后观察小鼠踝关节滑膜组织病理学变化,并采用Western blot法检测小鼠滑膜组织中NF-κB p65蛋白表达。结果:与正常组比较,模型组小鼠在给药不同时间后的AI值、脾指数、胸腺指数、血清中炎症因子(IL-1β、IL-6、TNF-α)以及滑膜组织中NF-κB p65蛋白表达水平均显著升高(P<0.05);小鼠踝关节滑膜组织出现细胞排列密集且紊乱、滑膜细胞数量增加、充血等病理学变化。与模型组比较,除GSM低剂量组小鼠在给药7、14 d的AI值降低不显著外,各给药组小鼠其余指标水平均显著降低(P<0.05);各给药组小鼠踝关节滑膜组织的充血程度减轻、炎性细胞数量减少。结论:GSM可能通过降低血清中炎症因子水平,抑制滑膜组织中NF-κB p65蛋白表达,进一步减轻滑膜炎症而发挥其抗RA的作用。
ABSTRACT: OBJECTIVE: To investigate the effects of the ethanol extract of Tibetan medicine Gentiana straminea (GSM) on the expression of NF-κB p65 in synovial tissue of collagen-induced arthritis (CIA) model mice, and to provide a reference for elucidating the action mechanism of its anti-rheumatoid arthritis (RA). METHODS: Totally 40 mice were randomly divided into normal group, model group, dexamethasone group (positive drug, 0.25 mg/kg) and GSM low-dose and high-dose groups (25, 50 mg/kg, calculated by crude drug), with 8 mice in each group. Except for normal group, other groups were given intradermal injection of Chicken type Ⅱ collagen intracutaneously via tail to induce CIA model. After modeling, medication group was given relevant medicine intragastrically once a day, and normal group and model group were given same amount of normal saline intragastrically for consecutive 28 d. The arthritis index (AI) of mice were determined 7, 14, 28, 35 d after medication. After last medication, the spleen index and thymus index of mice were determined; ELISA was used to measure the serum levels of IL-1β, IL-6 and TNF-α; Pathological change of synovial tissue in ankle joint of mice was observed by HE staining; Western blot was used to detect the protein expression of NF-κB p65 in synovial tissue of mice. RESULTS: Compared with normal group, the levels of AI value after different medication time, and spleen index, thymus index, serum inflammatory factors (IL-1β, IL-6, TNF-α) and protein expression of NF-κB p65 in synovial tissue were increased significantly in model group (P<0.05). Pathological changes of synovial tissue in mice were observed, such as dense and disorder cell arrangement, the increase of synovial cells, hyperemia. Compared with model group, decrease of AI was not significant in GSM low-dose group 7, 14 d after medication, and other indexes of medication groups were all decreased significantly (P<0.05). The inflammatory cell hyperplasia and the number of inflammatory cells were decreased in medication groups. CONCLUSIONS: GSM can inhibit the protein expression of NF-κB p65 in synovial tissue and relieve synovial inflammation and play its role on the anti RA by reducing the levels of serum inflammatory factors.
期刊: 2018年第29卷第15期
作者: 贾娜,崔佳,文爱东
AUTHORS: JIA Na,CUI Jia,WEN Aidong
关键字: 藏药;麻花秦艽醇提物;胶原诱导型关节炎;小鼠;核转录因子κB p65
KEYWORDS: Tibetan medicine; Ethanol extract of Gentiana stramine; Collagen-induced arthritis; Mice; NF-κB p65
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