Kanezuka T, Hatanaka Y
Biological Section, Research Laboratory of Grelan Pharmaceutical Co., Ltd., Tokyo, Japan.
Nihon Yakurigaku Zasshi. 1988 Aug;92(2):127-43. doi: 10.1254/fpj.92.127.
The progress of various symptoms in adjuvant arthritic rats (AA-rats) and the effects of anti-rheumatic drugs were continuously observed on the basis of the Weibull distribution function, and the following results were obtained: 1) The cumulative incidence rates F(t) of various symptoms and abnormalities of measured values gradually increased with the passage of time. The relationship between the F(t) and the days after adjuvant injection indicated a simple Weibull distribution function. On the other hand, the bone damages in the distal limb joints indicated a composite Weibull distribution function with two shape parameters (m1 and m2). It was possible to classify the animals into two groups, fast responders (m1) and slow responders (m2), according to the time of occurrence of bone damages. 2) By using the Weibull probability paper, it was possible to integrate and to evaluate in totality those cases with varying grades of symptoms and cases with different symptoms in the adjuvant-induced syndrome in rats. 3) Azathioprine (AZP) showed an inhibitory effect on the advents of pain and swelling and functional disorders, while indomethacin (IDM), prednisolone (PSL) and gold sodium thiomalate (GST) delayed the advents of these symptoms. As to bone damages in the distal limb joints, IDM, PSL and AZP showed an inhibitory effect in only the fast responder group, while GST showed both an inhibitory and delaying effect in both the fast responder group and the slow one. The above results suggest that the usage of the Weibull distribution function is useful not only for analysis of the morbid condition of AA-rats but also for the evaluation of anti-rheumatic drugs in AA-rats.
基于威布尔分布函数,持续观察佐剂性关节炎大鼠(AA大鼠)各种症状的进展以及抗风湿药物的效果,获得以下结果:1)各种症状及测量值异常的累积发生率F(t)随时间推移逐渐增加。F(t)与佐剂注射后天数之间的关系呈简单的威布尔分布函数。另一方面,远端肢体关节的骨损伤呈具有两个形状参数(m1和m2)的复合威布尔分布函数。根据骨损伤发生时间,可将动物分为两组,即快速反应者(m1)和缓慢反应者(m2)。2)通过使用威布尔概率纸,可以对大鼠佐剂诱导综合征中症状程度不同的病例以及症状不同的病例进行整合和总体评估。3)硫唑嘌呤(AZP)对疼痛、肿胀及功能障碍的出现有抑制作用,而吲哚美辛(IDM)、泼尼松龙(PSL)和硫代苹果酸金钠(GST)可延迟这些症状的出现。至于远端肢体关节的骨损伤,IDM、PSL和AZP仅在快速反应者组显示抑制作用,而GST在快速反应者组和缓慢反应者组均显示抑制和延迟作用。上述结果表明,威布尔分布函数的应用不仅有助于分析AA大鼠的病情,也有助于评估AA大鼠中的抗风湿药物。