新风胶囊通过Toll样受体4/核因子κB通路改善佐剂性关节炎大鼠模型心血管功能的机制研究

Mechanism studies of Xinfeng capsule on improving cardiovascular function though toll-like receptor 4/nuclear factor kappa B pathway in a rat model of adjuvant arthritis.

作者信息

Wang Yuan, Liu Jian, Huang Chuanbing, Sun Yue, Zhang Wandong, Wan Lei, Zong Ruikai, Wang Yali

出版信息

J Tradit Chin Med. 2017 Feb;37(1):116-23. doi: 10.1016/s0254-6272(17)30035-3.

DOI:10.1016/s0254-6272(17)30035-3

PMID:29957982

Abstract

OBJECTIVE

To observe the impact of Xinfeng capsule (XFC) on cardiovascular function in adjuvant arthritis (AA) model rats and investigate the mechanism though toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling pathway.

METHODS

Seventy rats were randomly divided into seven groups: normal control (NC), model control (MC), tripterygium glycosides tablet (TPT), methotrexate (MTX), high, moderate and low dose XFC group. The administration began from day 19 after modeling for 30 day. Paw swelling, arthritic index (AI), cardiac function indexes and myocardial pathological pattern were detected. The expression of TLR4, myeloid differentiation factor (MyD) 88, interleukin-1 receptor-associated kinase (IRAK) 1, tumor necrosis factor receptor associated factor (TRAF) 6, NF-κB, tumor necrosis factor-alpha (TNF-α) proteins in myocardial tissue were determined by western blot method.

RESULTS

Paw swelling and AI in MC group increased in MC group (P < 0.01), and decreased in high and moderate dose XFC groups (P < 0.01 or P > 0.05). Left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), heart rate (HR) were elevated in MC group (P < 0.01), and ± dp/dtmax and CI were reduced (P < .01); while LVSP, LVEDP and HR declined and ±dp/ dtmax, CI improved in high dose XFC group (P < 0.05 or P < 0.01). LVSP in high dose XFC group were reduced more than other treatment groups (P < 0.05 or P < 0.01). The improvements on LVEDP, dp/ dt-max were superior to MTX and low dose XFC group, and the improvement on CI was better than low dose XFC group (P < 0.05 or P < 0.01). Myocardial fibers arranged irregular in MC group with intracellular edema and mitochondria damage. The modifications on myocardial structural were shown in each treatment group, but more prominent in TPT, high and moderate dose XFC group. The proteins of TLR4, MyD88, IRAK1, TRAF6, NF-κB, TNF-α were highly expressed in MC group, and those proteins declined in high and moderate dose XFC group (P < 0.05 or P < 0.01). High dose XFC group was superior to MTX and low dose XFC group on reducing TLR4, NF-κB, TNF-α (P < 0.05).

CONCLUSION

XFC can not only inhibit the excessive activation of TLR4/NF-κB signaling pathway and the increased inflammatory mediators, but also reduce the damage of myocardial tissue and cells.

摘要

目的

观察新风胶囊（XFC）对佐剂性关节炎（AA）模型大鼠心血管功能的影响，并通过Toll样受体4（TLR4）/核因子κB（NF-κB）信号通路探讨其作用机制。

方法

将70只大鼠随机分为7组：正常对照组（NC）、模型对照组（MC）、雷公藤多苷片组（TPT）、甲氨蝶呤组（MTX）、XFC高、中、低剂量组。造模后第19天开始给药，持续30天。检测 paw肿胀度、关节炎指数（AI）、心功能指标及心肌病理形态。采用蛋白质免疫印迹法测定心肌组织中TLR4、髓样分化因子（MyD）88、白细胞介素-1受体相关激酶（IRAK）1、肿瘤坏死因子受体相关因子（TRAF）6、NF-κB、肿瘤坏死因子-α（TNF-α）蛋白的表达。

结果

MC组 paw肿胀度和AI升高（P < 0.01），XFC高、中剂量组降低（P < 0.01或P > 0.05）。MC组左心室收缩压（LVSP）、左心室舒张末期压力（LVEDP）、心率（HR）升高（P < 0.01），±dp/dtmax和心脏指数（CI）降低（P < 0.01）；XFC高剂量组LVSP、LVEDP和HR下降，±dp/dtmax、CI改善（P < 0.05或P < 0.01）。XFC高剂量组LVSP降低幅度大于其他治疗组（P < 0.05或P < 0.01）。XFC高剂量组对LVEDP、dp/dt-max的改善优于MTX组和XFC低剂量组，对CI的改善优于XFC低剂量组（P < 0.05或P < 0.01）。MC组心肌纤维排列不规则，细胞内水肿，线粒体损伤。各治疗组均显示对心肌结构有改善，TPT组、XFC高、中剂量组更为明显。MC组TLR4、MyD88、IRAK1、TRAF6、NF-κB、TNF-α蛋白高表达，XFC高、中剂量组这些蛋白表达下降（P < 0.05或P < 0.01）。XFC高剂量组在降低TLR4、NF-κB、TNF-α方面优于MTX组和XFC低剂量组（P < 0.05）。