【摘要】：目的:草酸鉑屬于第三代鉑類制劑,在轉(zhuǎn)移性大腸癌的治療中占有重要地位,周圍神經(jīng)系統(tǒng)毒性為其劑量限制性毒性。本實(shí)驗(yàn)旨在探討草酸鉑致大鼠周圍神經(jīng)系統(tǒng)毒性損害的病理學(xué)改變是否具有可恢復(fù)的趨勢及藥物劑量依賴性的特點(diǎn),以及在草酸鉑應(yīng)用期間大鼠后根神經(jīng)節(jié)內(nèi)神經(jīng)生長因子表達(dá)的變化規(guī)律,并進(jìn)一步探討神經(jīng)生長因子表達(dá)的變化規(guī)律與草酸鉑周圍神經(jīng)系統(tǒng)毒性損害的靶器官—后根神經(jīng)節(jié)內(nèi)的神經(jīng)元形態(tài)改變之間的關(guān)系。 方法:動物實(shí)驗(yàn)分兩部分進(jìn)行:A組:Wistar雌性成年大鼠96 只,隨機(jī)分為兩組:空白對照組及實(shí)驗(yàn)組,每組48 只。兩組再分別隨機(jī)分為12個小組,分別代表12個時間點(diǎn),實(shí)驗(yàn)組大鼠腹腔注射草酸鉑20mg/kg,實(shí)驗(yàn)組與空白對照組大鼠均在以上時間點(diǎn)取左側(cè)L4-5后根神經(jīng)節(jié)及左側(cè)坐骨神經(jīng)。B 組:Wistar 雌性成年大鼠24 只,隨機(jī)分為6 組,除空白對照組外,其余5 組大鼠分別腹腔注射草酸鉑1mg/kg5mg/kg、10mg/kg、20mg/kg 、30mg/kg,用藥后24小時取左側(cè)L4-5后根神經(jīng)節(jié)及左側(cè)坐骨神經(jīng)。獲取組織分別進(jìn)行石蠟切片及電鏡超薄切片的制作,之后利用HE 染色法光鏡技術(shù)透射電鏡技術(shù)以及免疫組織化學(xué)染色的方法觀察大鼠后根神經(jīng)節(jié)內(nèi)的感覺神經(jīng)元及坐骨神經(jīng)在草酸鉑不同應(yīng)用劑量及不同時間點(diǎn)的病理學(xué)改變以及后根神經(jīng)節(jié)內(nèi)神經(jīng)生長因子的表達(dá)隨時間和不同藥物劑量的變化規(guī)律,并利用圖
[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
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2005
【分類號】：R363

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