草酸铂致大鼠周围神经系统毒性的病理学及神经生物学研究

发布时间：2019-03-08 09:52

【摘要】：目的:草酸铂属于第三代铂类制剂,在转移性大肠癌的治疗中占有重要地位,周围神经系统毒性为其剂量限制性毒性。本实验旨在探讨草酸铂致大鼠周围神经系统毒性损害的病理学改变是否具有可恢复的趋势及药物剂量依赖性的特点,以及在草酸铂应用期间大鼠后根神经节内神经生长因子表达的变化规律,并进一步探讨神经生长因子表达的变化规律与草酸铂周围神经系统毒性损害的靶器官—后根神经节内的神经元形态改变之间的关系。方法:动物实验分两部分进行:A组:Wistar雌性成年大鼠96 只,随机分为两组:空白对照组及实验组,每组48 只。两组再分别随机分为12个小组,分别代表12个时间点,实验组大鼠腹腔注射草酸铂20mg/kg,实验组与空白对照组大鼠均在以上时间点取左侧L4-5后根神经节及左侧坐骨神经。B 组:Wistar 雌性成年大鼠24 只,随机分为6 组,除空白对照组外,其余5 组大鼠分别腹腔注射草酸铂1mg/kg5mg/kg、10mg/kg、20mg/kg 、30mg/kg,用药后24小时取左侧L4-5后根神经节及左侧坐骨神经。获取组织分别进行石蜡切片及电镜超薄切片的制作,之后利用HE 染色法光镜技术透射电镜技术以及免疫组织化学染色的方法观察大鼠后根神经节内的感觉神经元及坐骨神经在草酸铂不同应用剂量及不同时间点的病理学改变以及后根神经节内神经生长因子的表达随时间和不同药物剂量的变化规律,并利用图
[Abstract]:Aim: oxaliplatin is a third generation platinum preparation, which plays an important role in the treatment of metastatic colorectal cancer, and peripheral nervous system toxicity is its dose-limiting toxicity. The aim of this study was to investigate whether the pathological changes of peripheral nervous system toxicity in rats induced by oxaliplatin had a recoverable tendency and the characteristics of drug dose dependence. And the changes of nerve growth factor expression in the rat posterior root ganglion during the administration of oxaliplatin. Furthermore, the relationship between the changes of nerve growth factor expression and the morphological changes of neurons in the posterior root ganglion, the target organ of toxic damage of peripheral nervous system induced by oxaliplatin, was further investigated. Methods: the animal experiment was divided into two parts: group A: 96 adult female Wistar rats were randomly divided into two groups: blank control group and experimental group with 48 rats in each group. The rats in the experimental group were intraperitoneally injected with oxaliplatin 20 mg 路kg-1, respectively, on behalf of 12 time points, and the rats in the experimental group were injected intraperitoneally with 20 mg oxaliplatin. The left root ganglia and the left sciatic nerve were taken from the left L4? 5 posterior root ganglion and the left sciatic nerve at the above time in both the experimental group and the blank control group. Group B: 24 adult female Wistar rats were randomly divided into 6 groups, except the blank control group. The other 5 groups were intraperitoneally injected with oxaliplatin 1 mg / kg, 10 mg / kg, 20 mg / kg, 30 mg / kg respectively. The left root ganglia and left sciatic nerve were taken 24 hours after administration. The tissues were made into paraffin sections and ultrathin sections under electron microscope, and then were stained by HE. Light microscopy? Observation of the pathological changes of sensory neurons and sciatic nerve in the posterior root ganglia of rats by transmission electron microscopy and immunohistochemical staining at different dosage and time points of oxaliplatin application and in the posterior root ganglia The expression of nerve growth factor changes with time and dose of different drugs. And use the graph
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2005
【分类号】：R363

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