Fang Li, Liu Jian, Zhu Fu-Bing
Zhongguo Zhong Xi Yi Jie He Za Zhi. 2016 Oct;36(10):1202-1207.
Objective To observe the effect of Xinfeng Capsule (XFC) on related factors of thrombus formation and inflammatory cytokines in active ankylosing spondylitis (AS) patients. Methods Seventy-six active AS patients were assigned to the XFC group and the Sulfasalazine treated group (SASP group) , 38 in each group according to random digits table. Patients in the SASP group took SASP, 0. 25 g per tablet, 4 tablets each time, twice per day. Those in the XFC group took XFC, 0. 5 g per pill, 3 pills each time, three times per day. All medication lasted for 12 successive weeks. Platelet count and coagulation functions were determined. Factors of thrombus formation [including thromboxane B2(TXB2), prostaglan- din 1₂ (PG1₂), 6-ketone-prostaglandin F1 (6-keto-PGF1) , platelet granular membrane protein140 (GMP140), plasminogen activator inhibitor 2 (PAI-2 ) ], erythrocyte sedimentation rate (ESR), C reactive protein (CRP) , and levels of cytokines (TNF-α, IL-4, IL-10, IL-17) were detected. mRNA expressions of nuclear factor activator (Act1) , NF-κB inhibitory protein-alpha (IKBα) , inhibitor of kappa-B kinase beta (IKKβ) , NF-κB protein 65 (NF-κB/P65), and NF-κB protein 50 (NF-κB/P50) were detected by real-time fluorescent quantitative PCR (RT-PCR). Meanwhile, the protein expression of NF-κB/P65 and NF-κB/P50 were detected by Western blot. Results Compared with before treatment in the same group, levels of PLT, fibrinogen (FBG), D-dimer (DD), TXB₂, GMP140, and PAI-2 were significantly decreased, but 6-keto-PGF1 level was significantly increased in XFC group after treatment (P <0. 01). Besides, the improvement of above indices was significantly superior in the XFC group to SASP group in the same period (all P <0. 01). Compared with before treatment and SASP group after treatment, IL-17 level was significantly decreased, IL-4 and IL-10 were significantly increased, levels of ESR and CRP decreased in the XFC group after treatment (P <0. 05, P <0. 01). Compared with before treatment in the same group, mRNA expressions of Act1, IKKβ, IKBα, NF- κB/P50, and NF-κB/P65, and protein expressions of NF-κB/P65 and NF-κB/P50 were obviously reduced in the two groups after treatment (P <0. 05, P <0. 01). Besides, mRNA expressions of lKKβ, IKBα, NF-κB/ P50, and NF-κB/P65, and protein expressions of NF-κB/P65 and NF-κB/P50 were more obviously reduced in the XFC group than in the SASP group (P <0. 05, P <0. 01). Conclusions XFC could improve thrombosis re- lated factors in AS patients. Its mechanism might be associated with regulating cytokines and inhibiting ex- cessive activation of NF-κB signal pathway.
目的 观察新风胶囊(XFC)对活动期强直性脊柱炎(AS)患者血栓形成相关因子及炎性细胞因子的影响。方法 将76例活动期AS患者按随机数字表法分为XFC组和柳氮磺吡啶治疗组(SASP组),每组38例。SASP组患者服用SASP,每片0.25 g,每次4片,每日2次。XFC组患者服用XFC,每丸0.5 g,每次3丸,每日3次。所有药物均连续服用12周。测定血小板计数及凝血功能。检测血栓形成相关因子[包括血栓素B2(TXB2)、前列环素I₂(PGI₂)、6-酮-前列腺素F1(6-酮-PGF1)、血小板颗粒膜蛋白140(GMP140)、纤溶酶原激活物抑制剂2(PAI-2)]、红细胞沉降率(ESR)、C反应蛋白(CRP)及细胞因子(TNF-α、IL-4、IL-10、IL-17)水平。采用实时荧光定量PCR(RT-PCR)检测核因子激活剂(Act1)、NF-κB抑制蛋白α(IKBα)、κB抑制激酶β(IKKβ)、NF-κB蛋白65(NF-κB/P65)及NF-κB蛋白50(NF-κB/P50)的mRNA表达。同时,采用蛋白质印迹法检测NF-κB/P65及NF-κB/P50的蛋白表达。结果 与同组治疗前比较XFC组治疗后PLT、纤维蛋白原(FBG)、D-二聚体(DD)、TXB₂、GMP140及PAI-2水平显著降低,6-酮-PGF1水平显著升高(P<0.01)。此外,同期XFC组上述指标改善情况显著优于SASP组(均P<0.01)。与治疗前及SASP组治疗后比较,XFC组治疗后IL-17水平显著降低,IL-4及IL-10显著升高,ESR及CRP水平降低(P<0.05,P<0.01)。与同组治疗前比较,两组治疗后Act1、IKKβ、IKBα、NF-κB/P50及NF-κB/P65的mRNA表达及NF-κB/P65、NF-κB/P50的蛋白表达均明显降低(P<0.05,P<0.01)。此外,XFC组IKKβ、IKBα、NF-κB/P50及NF-κB/P65的mRNA表达及NF-κB/P65、NF-κB/P50的蛋白表达降低更明显,与SASP组比较差异有统计学意义(P<0.05,P<0.01)结论 XFC可改善AS患者血栓形成相关因子。其机制可能与调节细胞因子及抑制NF-κB信号通路过度激活有关。