猴体神经毒力实验组织病理学评价方法的建立

发布时间：2018-07-12 11:45

本文选题：疫苗 + 神经毒力　；参考：《中国新药杂志》2014年18期

【摘要】：目的:建立一种猴体神经毒力实验的组织病理学评价方法,用于疫苗猴体神经毒力非临床安全性评价。方法:通常采用猴丘脑内和脊髓腰椎段注射给予疫苗。给药结束后,猴体经解剖,取材,脱水,包埋,切片,HE染色后在光镜下观察神经组织病理学改变。病变按规定的神经毒性诊断标准打分后用Ridit方法进行组间比较检验,最终对所观察到的神经组织病变的统计结果进行分析和评价。结果:本方法中,脑组织取材包括左右两侧大脑在内的14个切面以及小脑、脑桥1个切面和延髓2个切面;脊髓取材包括颈髓5个切面、胸髓3个切面和腰髓6个切面。以上所取切面涵盖了神经组织的基本结构功能区域,操作简单且实用。组织病理学检查将神经组织病变分类为神经元变性、坏死,嗜神经现象,神经胶质细胞增多,小胶质细胞结节,围管浸润和针迹反应等。这些病变按病变数目和病灶面积进行等级划分,从"0"分到"4"分共分为5个等级。结论:神经系统的形态学评价要求病理实验人员熟悉大脑的结构和功能,掌握解剖及病理制片技能。因此,神经组织病理制片的科学性和一致性以及操作人员的技术水平影响神经毒性组织病理学评价的可靠性和准确性。本研究建立的神经毒力组织病理学评价方法除适用于疫苗猴体神经毒力非临床安全性评价实验外,还可应用于一般神经毒性实验、神经组织退行性疾病动物模型以及脑、脊髓损伤动物模型的评价中,是一项系统、规范、实用的神经毒性组织病理学评价方法。
[Abstract]:Objective: to establish a method for histopathological evaluation of somatic neurovirulence in monkeys. Methods: the vaccine was usually injected into the thalamus and spinal cord of monkeys. After administration, the monkey body was dissected, sampled, dehydrated, embedded, stained with HE and observed the pathological changes of nerve tissue under light microscope. The pathological changes were graded according to the prescribed criteria of neurotoxicity and compared with each other by Ridit method. Finally, the statistical results of the observed neuropathy were analyzed and evaluated. Results: in this method, 14 sections and cerebellum, 1 pons and 2 medulla oblongata were selected from brain tissue, 5 sections from cervical spinal cord, 3 from thoracic spinal cord and 6 from lumbar spinal cord. The above section covers the basic structure and function area of neural tissue and is simple and practical. Histopathological examination classified neuropathy as neuronal degeneration, necrosis, neurophilic phenomenon, glial cell proliferation, microglial nodule, perivascular infiltration and Needle reaction. These lesions were divided into 5 grades according to the number of lesions and the area of lesions, from "0" to "4". Conclusion: the morphological evaluation of the nervous system requires the pathologists to be familiar with the structure and function of the brain and to master the skills of anatomy and pathology. Therefore, the reliability and accuracy of neurotoxic histopathological evaluation are affected by the scientific and consistent nature of neuropathology and the technical level of operators. The neurovirulence histopathological evaluation method established in this study can be used not only for the non-clinical safety evaluation of the body neurovirulence of the vaccine monkey, but also for the general neurotoxicity test, the animal model of neurodegenerative diseases and the brain. In the evaluation of spinal cord injury animal model, it is a systematic, standard and practical method for evaluating neurotoxicity histopathology.
【作者单位】：中国食品药品检定研究院国家药物安全评价监测中心;
【基金】：国家“重大新药创制”科技重大专项药物安全评价技术平台 2012ZX09302001
【分类号】：R361.2

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