从β-内啡肽的表达探讨华蟾素治疗癌痛的外周机制研究-药理学专业论文.docxVIP

而对血浆中β-END、CRF、肿瘤及周围组织匀浆和血浆中的IL-1β的含量影响较小。 5、右后足肿瘤及周围组织中β-END、POMC和μ-阿片受体的表达结果：免疫组化 结果显示，正常对照组中的小鼠足组织中β-END、POMC和μ-阿片受体的表达均较高， 而癌痛模型小鼠的足肿瘤及周围组织中的β-END、POMC和μ-阿片受体的表达显著下 降，且与正常组比较，具有显著统计学意义（p0.01）。而华蟾素则可显著地提高癌 痛小鼠肿瘤及周围组织中β-END、POMC和μ-阿片受体的表达，且与模型组比较，具 有统计学意义（p0.01）。 结论：1、本实验制备的癌痛模型既表现了热痛觉过敏，又表现出了机械性痛觉 过敏，同时还出现了“镜像痛”现象。后足的形态学观察发现，右后足癌细胞最终侵 润到骨，说明该癌痛模型制备较为成功，可作为研究治疗癌痛药物的模型。 2、华蟾素能够改善癌痛模型小鼠的症状，显著提高癌痛小鼠的痛阈值，其机制 可能与增加肿瘤及周围组织中β-END的含量有关，具体如下：可提高癌痛小鼠的脾和 胸腺指数，增强癌痛小鼠的免疫功能；可提高癌痛小鼠足肿瘤及周围组织中POMC的 表达、CRF的含量，增加β-END的合成以及释放，从而增加肿瘤及周围组织中β-END 的含量；可增加肿瘤及周围组织中μ-阿片受体的表达，最终增加β-END与μ-阿片受体 在肿瘤及周围组织中的结合机会，发挥外周镇痛作用。 关键词：华蟾素 癌痛模型 外周阿片受体 β-内啡肽 阿黑皮素原 Abstract Objective In this study, the peripheral mechanisms of Huachansu curing cancer pain were investigated from the expression of β-END based on establishing the mouse model of hindpaw cancer pain. Methods 1. The make of the mouse model of hindpaw cancer pain: After selecting 22 female mice, their right hindpaws were injected into the suspension of H22 hepatoma cells, while the left hindpaws were injected into saline as control. The pain behavior and swell of hindpaws of each mouse were tested before modeling and on the day of 2, 4, 6, 8, 10, 12, 20, 30 after modeling, respectively. Moreover, mouse was killed by cervical dislocation in accordance with a regular interval time to observe the morphology of hindpaw by HE staining. 2. The peripheral mechanisms of Huachansu curing the mouse model of cancer pain: 60 female mice were randomly divided into normal control group, model group, the group of Huachansu, the group of Huachansu combined with NAL-M, the group of morphine, 12 mice in each group. From the nineth day after making the model, the mice in normal group were administered with saline by ip, and the mice in model group were administered with injection of saline combined with saline, Huachansu combined with saline, Huachansu combined with NAL-M, morphine combined with saline by ip for 8 days, respectively. The pain behavior of each mou