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体重和身体状况对链脲佐菌素大鼠模型中疼痛性糖尿病神经病变行为测试的影响。

The impact of bodyweight and body condition on behavioral testing for painful diabetic neuropathy in the streptozotocin rat model.

作者信息

Hoybergs Yves M J J, Biermans Ria L V, Meert Theo F

机构信息

CNS Discovery Research, Johnson & Johnson Pharmaceutical Research & Development, Turnhoutseweg 30, B-2340 Beerse, Belgium.

出版信息

Neurosci Lett. 2008 May 2;436(1):13-8. doi: 10.1016/j.neulet.2008.02.051. Epub 2008 Mar 4.

Abstract

The streptozotocin (STZ)-induced diabetes model is widely used for the induction of neuropathy in the rat. In this model, diabetic animals often display chronic illness, which raises objections not only on ethical but also on scientific grounds. In this study, the investigators set out to determine the impact of bodyweight and body condition (BC) on behavioral testing in the rat. Animals were allocated to four different groups as a function of their bodyweight, in particular one control group and three experimental groups with different starting weights (low bodyweight [LBW], medium bodyweight [MBW] and high bodyweight [HBW]), the groups having been rendered diabetic with an intraperitoneal injection of STZ (65mg/kg). Bodyweight, blood glucose, body condition and thresholds for mechanical hyperalgesia and tactile allodynia were measured or evaluated over a 68-day period. Animals with a LBW at the start of the experiment showed a gradual increase in BW with a decrease in mechanical nociceptive thresholds, while MBW and HBW animals presented a decrease in both thresholds and BW. The body condition score (BCS) decreased in all STZ-treated groups over time. Since correlations between mechanical thresholds and BW were similar between the control group and the HBW and MBW groups, the loss in BW clearly contributed to the decrease in thresholds. In the LBW group, thresholds and BW correlated negatively, so that the decrease in thresholds was mainly caused by the development of a painful neuropathy. From an ethical and a scientific point of view, in the STZ-induced diabetic neuropathy model, animals should be chosen on the basis of bodyweight and it must also be ensured that STZ is correctly dosed.

摘要

链脲佐菌素(STZ)诱导的糖尿病模型被广泛用于诱导大鼠神经病变。在该模型中,糖尿病动物常表现出慢性疾病,这不仅在伦理方面,而且在科学方面都引发了异议。在本研究中,研究人员着手确定体重和身体状况(BC)对大鼠行为测试的影响。根据体重将动物分为四个不同组,特别是一个对照组和三个起始体重不同的实验组(低体重[LBW]、中等体重[MBW]和高体重[HBW]),通过腹腔注射STZ(65mg/kg)使这些组患糖尿病。在68天的时间内测量或评估体重、血糖、身体状况以及机械性痛觉过敏和触觉异常性疼痛的阈值。实验开始时体重低的动物体重逐渐增加,机械性伤害感受阈值降低,而中等体重和高体重的动物阈值和体重均降低。随着时间的推移,所有经STZ处理的组的身体状况评分(BCS)均下降。由于对照组与高体重和中等体重组之间机械阈值与体重的相关性相似,体重下降显然导致了阈值降低。在低体重组中,阈值与体重呈负相关,因此阈值降低主要是由疼痛性神经病变的发展引起的。从伦理和科学的角度来看,在STZ诱导的糖尿病神经病变模型中,应根据体重选择动物,并且还必须确保正确给予STZ剂量。

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