Zhu Xianjin, Zhang Jie, Huo Rongfen, Lin Jinpiao, Zhou Zhou, Sun Yue, Wu Pinru, Li Huidan, Zhai Tianhang, Shen Baihua, Li Ningli
Shanghai Institute of Immunology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Affiliated Union Hospital of Fujian Medical University, Fuzhou, China.
Shanghai Institute of Immunology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
J Ethnopharmacol. 2014 Dec 2;158 Pt A:283-90. doi: 10.1016/j.jep.2014.10.021. Epub 2014 Oct 29.
Tripterygium preparations (TPs), a traditional Chinese Medicines extracted from Tripterygium wilfordii Hook f., are widely used for treatment of rheumatoid arthritis (RA). However, TPs from different Pharmaceutical factory have different efficacy and side effects for RA treatment.
The purpose of the current study is to evaluate the efficacy and safety of four TPs from different Pharmaceutical factory in china on the treatment of collagen-induced arthritis (CIA) rats and provide a theoretical and experimental basis for the individualized use of TPs.
The model of wistar rats of CIA was made, and the rats were perfused a stomach with four TPs for 3 weeks continuously. Then arthritis severity was determined by visual examination of the paws and histopathologic changes of joint, liver, kidney and testis were determined by hematoxylin-eosin (H&E) staining. The expression of inflammatory cytokines (IL-1β, TNF-α, IL-17 and IL-6) in the joint was analyzed by real-time PCR, and the count and motion parameters (sperm motility and progressive sperm) of sperm in cauda epididymis were assessed with computer-assisted sperm analysis (CASA) system. Routine blood tests were conducted using automated hematology analyzer, and the aspartate aminotransferase (AST), alanine aminotransferase (ALT) activities, creatinine (Cr), and blood urea nitrogen (BUN) in serum of CIA rats were measured using a UniCel DxC 880i autoanalyzer.
All of tested TPs could reduce inflammatory score, histopathological arthritis severity and joint׳s inflammatory cytokines (IL-1β, TNF-α, IL-17 and IL-6) expression in CIA rats, however, TP-D showed stronger inhibitory effect for inflammatory score compared with other three TPs in vivo. All of tested TPs did not show hepatotoxicity and nephrotoxicity and also had little effect for the concentration of hemoglobin (Hb) and the count of white blood cell (WBC). Analysis of red blood cell (RBC) number showed that TP-C and TP-D could reverse lower RBC number in untreated CIA rats to normal level. Interestingly, the results showed TPs named TP-C and TP-D could decrease platelet (PLT) number which significantly increases in untreated CIA rats. Reproductive toxicity, the main side effect of TPs, assay showed that the sperm quality (density, viability, and motility) in four of TPs-treated CIA rats were decreased significantly, consistently with spermatogenic cell density reduced. However parallel analysis showed that in four TPs-treated rats, the number of sperm, motile sperm and progressive sperm were highest in TP-D group, in contrast, were lowest in TP-C group.
These findings suggested that four TPs showed significantly therapeutic effect on ameliorating inflammation of CIA rats, with no obvious hepatotoxicity and nephrotoxicity in vivo. TP-D showed advantages with its higher efficacy and less reproductive toxicity as well as increasing RBC number, decreasing PLT number in CIA treatment. Thus, in the development of individualized treatment plan for RA patients, TP-D might be considered preferentially.
雷公藤制剂（TPs）是从雷公藤中提取的传统中药，广泛用于治疗类风湿性关节炎（RA）。然而，不同药厂生产的TPs在治疗RA时疗效和副作用存在差异。
本研究旨在评估中国不同药厂生产的四种TPs对胶原诱导性关节炎（CIA）大鼠的治疗效果和安全性，为TPs的个体化应用提供理论和实验依据。
建立CIA的Wistar大鼠模型，连续3周给大鼠灌胃四种TPs。然后通过肉眼观察爪子来确定关节炎严重程度，通过苏木精-伊红（H&E）染色确定关节、肝脏、肾脏和睾丸的组织病理学变化。通过实时PCR分析关节中炎性细胞因子（IL-1β、TNF-α、IL-17和IL-6）的表达，并用计算机辅助精子分析（CASA）系统评估附睾尾精子的数量和运动参数（精子活力和前向运动精子）。使用自动血液分析仪进行血常规检测，使用UniCel DxC 880i自动分析仪测量CIA大鼠血清中的天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）活性、肌酐（Cr）和血尿素氮（BUN）。
所有受试TPs均可降低CIA大鼠的炎症评分、组织病理学关节炎严重程度及关节炎性细胞因子（IL-1β、TNF-α、IL-17和IL-6）表达，但TP-D在体内对炎症评分的抑制作用比其他三种TPs更强。所有受试TPs均未表现出肝毒性和肾毒性，对血红蛋白（Hb）浓度和白细胞（WBC）计数也几乎没有影响。红细胞（RBC）数量分析表明，TP-C和TP-D可使未治疗的CIA大鼠较低的RBC数量恢复至正常水平。有趣的是，结果显示名为TP-C和TP-D的TPs可降低未治疗的CIA大鼠中显著升高的血小板（PLT）数量。生殖毒性是TPs的主要副作用，检测显示四种TPs治疗的CIA大鼠的精子质量（密度、活力和运动能力）均显著降低，与生精细胞密度降低一致。然而，平行分析表明，在四种TPs治疗的大鼠中，TP-D组的精子数量、活动精子和前向运动精子数量最高，相比之下，TP-C组最低。
这些发现表明，四种TPs对改善CIA大鼠炎症具有显著治疗作用，在体内无明显肝毒性和肾毒性。TP-D在治疗CIA时具有疗效更高、生殖毒性更小以及增加RBC数量、降低PLT数量的优势。因此，在为RA患者制定个体化治疗方案时，可优先考虑TP-D。
