药物非临床毒性试验周围神经系统组织病理学评估研究进展

Research progress in histopathology assessment of peripheral nervous system during nonclinical toxicity studies of drugs

药物非临床毒性试验周围神经系统(peripheral nervous system,PNS)组织病理学评估分为4种情况:未知或预期无神经毒性的一般毒性试验、可能有躯体神经毒性的一般毒性试验、可能有自主神经病的一般毒性试验以及预期有神经毒性作用的专门神经毒性试验。美国毒性病理学会(Society of Toxicologic Pathology,STP)推荐最佳实践建议的目的是确保在药物非临床一般毒性试验和专门神经毒性试验的4种情况下,对PNS组织进行一致性、高效率取材、处理和评估。综述了PNS解剖的基本结构、PNS毒性试验情况分类及取材建议、PNS毒性试验不同情况下最佳实践建议、PNS神经病理学评估分析策略以及评估结果的记录,以期为我国药物非临床毒性试验中周围神经系统组织病理学评估提供一定参考。

There are four different situations encountered in histopathology assessment of peripheral nervous system(PNS)during nonclinical toxicity studies,consisted of general toxicity studies where neurotoxicity is unknown or not anticipated,general toxicity studies where somatic PNS neurotoxicity is suspected,general toxicity studies where autonomic PNS neuropathy is suspected,and dedicated neurotoxicity studies where a neurotoxic effect is expected.Current best practice recommendations of the US Society of Toxicologic Pathology(STP)are designed to ensure consistent and efficient sampling,processing and evaluating of PNS tissues for the four different situations.The basic structure of PNS anatomy,different situations and recommendations for sampling of the PNS during toxicity studies,best practice recommendations for different situations of the PNS during toxicity studies,strategy for PNS neuropathology analysis,as well as neuropathology documentation are reviewed in the paper,in order to provide some references for histopathology assessment of PNS during nonclinical toxicity studies of drugs in China.