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[基于Actl/NF-KB信号通路的新风胶囊改善类风湿关节炎患者血瘀状态:机制与效应]

[Xinfeng Capsule Improved Blood Stasis State of Rheumatoid Arthritis Patients Based on Actl/NF-KB Signaling Pathway: Mechanism and Effects].

作者信息

Zhang Ping-Heng, Liu Jian, Tan Bin, Wan Lei

出版信息

Zhongguo Zhong Xi Yi Jie He Za Zhi. 2016 Aug;36(8):922-928.

Abstract

Objective To observe the mechanism of Xingfeng Capsule (XFC) for improving blood stasis state in rheumatoid arthritis (RA) patients based on Actl/NF-κB signaling pathway. Methods Totally 76 RA patients were equally assigned to two groups by random digit table, the XFC group (XFC, 3 pills each time, three times per day) and the Leflunomide group (LEF, 10 mg each time, once per day). All patients were intervened for 3 successive months. Clinical efficacy of symptoms of Chinese medicine (CM) was assessed. Serum levels of interleukin-10 (IL-10) , IL-17, IL-6, NF-κB activator 1 (Actl), p50, p65, platelet activating factor ( PAF) , platelet activating factor acetyl hydrolase ( PAF-AH) were detected using ELISA. Symptoms of blood stasis syndrome (BSS) were also assessed. mRNA expressions of Act1, p50, and p65 were detected using fluorescent quantitative PCR. Protein expressions of p50 and p65 were detected using Western blot. Correlation analyses were performed in RA patients' peripheral blood coagulation indicators, total score of BSS, and IL-1 0, IL-6, IL-17, Act1 , p50, p65 using Spearman. Results The total effective rate was 89. 5% (34t38) in the XFC group, with no statistical difference as compared with that of the LEF group [94. 7% (36)38), P >0. 05]. Compared with before treatment in the same group, serum levels of D-dimer (DD) , fibrinogen (FBG) , platelet (PLT) , PAF, IL-17, and IL-6 all decreased, mRNA expressions and serum levels of Act1, p50, and p65 were lowered, protein expres- sions of p50 and p65 decreased, scores for each symptoms in BSS all decreased, serum levels of PAF- AH and IL-10 increased in the two groups after treatment (P <0. 05, P <0. 01). Compared with the LEF group, serum levels of DD, FBG, PLT, IL-17, and IL-6 decreased, mRNA expressions and serum levels of Act1 and p65 were lowered, protein expression of p65 decreased, scores for joint prickling pain, tongue proper, subcutaneous ecchymosis, and BSS total score all decreased in the XFC group (P < 0. 05, P <0. 01). Peripheral blood DD was positively correlated with IL-17, IL-6, Act1, and and p65, but negatively correlated with IL-10 (P <0. 05, P <0. 01). FBG was positively correlated with IL-6 (P <0. 05). PLT was positively correlated with IL-17 (P <0. 05). BSS total score was positively correlated with IL-6, Act1, and p65, but negatively correlated with IL-10 (P <0. 05, P <0. 01). PAF was positively correlated with IL-17, IL-6, Act1 , and p65 (P <0. 05, P <0. 01), while PAF-AH was negatively correlated with p50 (P <0. 05). Conclusion The pathogenesis of BSS in RA patients and the effects of XFC on blood stasis state might be closely correlated to the Act1/NF-KB signaling pathway.

摘要

目的 基于Actl/NF-κB信号通路观察祛风胶囊(XFC)改善类风湿关节炎(RA)患者血瘀状态的机制。方法 将76例RA患者采用随机数字表法分为两组,即XFC组(XFC,每次3粒,每日3次)和来氟米特组(LEF,每次10 mg,每日1次)。所有患者连续干预3个月。评估中医症状的临床疗效。采用酶联免疫吸附测定法(ELISA)检测血清白细胞介素-10(IL-10)、IL-17、IL-6、NF-κB激活剂1(Actl)、p50、p65、血小板活化因子(PAF)、血小板活化因子乙酰水解酶(PAF-AH)水平。评估血瘀证症状。采用荧光定量聚合酶链反应(PCR)检测Act1、p50和p65的mRNA表达。采用蛋白质免疫印迹法检测p50和p65的蛋白表达。采用Spearman法对RA患者外周血凝血指标、血瘀证总分与IL-10、IL-6、IL-17、Act1、p50、p65进行相关性分析。结果 XFC组总有效率为89.5%(34/38),与LEF组[94.7%(36/38)]比较,差异无统计学意义(P>0.05)。与同组治疗前比较,两组治疗后血清D-二聚体(DD)、纤维蛋白原(FBG)、血小板(PLT)、PAF、IL-17和IL-6水平均降低,Act1、p50和p65的mRNA表达及血清水平降低,p50和p65的蛋白表达降低,血瘀证各症状积分均降低,血清PAF-AH和IL-10水平升高(P<0.05,P<0.01)。与LEF组比较,XFC组血清DD、FBG、PLT、IL-17和IL-6水平降低,Act1和p65的mRNA表达及血清水平降低,p65蛋白表达降低,关节刺痛、舌质、皮下瘀斑积分及血瘀证总分均降低(P<0.05,P<0.01)。外周血DD与IL-17、IL-6、Act1和p65呈正相关,与IL-10呈负相关(P<0.05,P<0.01)。FBG与IL-6呈正相关(P<0.05)。PLT与IL-17呈正相关(P<0.05)。血瘀证总分与IL-6、Act1和p65呈正相关,与IL-10呈负相关(P<0.05,P<0.01)。PAF与IL-17、IL-6、Act1和p65呈正相关(P<0.05,P<0.01),而PAF-AH与p50呈负相关(P<0.05)。结论 RA患者血瘀证的发病机制及XFC对血瘀状态的影响可能与Act1/NF-κB信号通路密切相关。

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