癌理通膏外敷治疗癌性疼痛的机制研究(1)
〔摘要〕 目的 观察癌理通膏对BALB/c癌性疼痛裸鼠的镇痛作用及对肿瘤生长、脊髓神经生长因子(NGF)、肿瘤坏死因子-α(TNF-α)、内皮素-1(ET-1)、β-内啡肽(β-EP)表达的影响。方法 通过在BALB/c裸鼠大腿外侧近臀部处皮下注射Walker 256乳腺癌细胞的方法建立裸鼠癌痛模型，动态观察癌理通组和模型组裸鼠的自发痛评分、肿瘤体积的变化，剥离肿瘤比较两组肿瘤重量的差异，RT-PCR法检测两组脊髓NGF、TNF-α、ET-1、β-EP的含量变化。结果 癌理通组裸鼠从第7天起自发痛评分明显低于模型组，持续到第10天(P<0.05)，肿瘤体积从第3天起明显小于模型组，持续到第10天(P<0.01)。与模型组比较，癌理通组肿瘤重量(P<0.01)、脊髓NGF(P<0.01)及TNF-α(P<0.05)的含量均明显下降，脊髓β-EP含量明显升高(P<0.05)，脊髓ET-1含量差异无统计学意义(P>0.05)。结论 癌理通膏能明显改善BALB/c裸鼠的癌性疼痛，其作用机制可能与癌理通膏抑制肿瘤的生长、降低脊髓NGF、TNF-α含量、升高脊髓β-EP的含量有关。
〔关键词〕 癌理通膏;癌性疼痛;肿瘤坏死因子-α;神经生长因子;β-内啡肽;内皮素-1
〔中图分类号〕R285.6 〔文献标志码〕A 〔文章编号〕doi：10.3969/j.issn.1674-070X.2020.07.012
〔Abstract〕 Objective To observe the analgesic effects of external application with Ailitong Ointment on BALB/c nude mouse with cancer pain and its impact on tumor growth， spinal nerve growth factor (NGF)， tumor necrosis factor alpha (TNF-α)， endothelin-1 (ET-1) and beta-endorphin (β-EP) expressions. Methods Walker 256 breast cancer cells were hypodermically injected in lateral thigh of BALB/c nude rats to establish nude rat model of cancer pain. The changes of spontaneous pain scores， gross tumor volume in the Ailitong group and the model group were dynamically observed. Tumor tissues were stripped to compare the tumor weight in the 2 groups; RT-PCR was used to detect the changes of spinal NGF， TNF-α， ET-1 and β-EP levels. Results From day 7 to day 10， spontaneous pain scores in the Ailitong group were significantly lower than the model group (P<0.05); From day 3 to day 10， tumor volume in the Ailitong group was significantly smaller than model group (P<0.01). Compared with the model group， the tumor weight (P<0.01)， NGF levels (P<0.01) and TNF-α levels (P<0.05) in the Ailitong group were significantly decreased; β-EP levels were significantly increased (P<0.05); ET-1 levels between the 2 groups were not significantly different (P>0.05). Conclusion Ailitong Ointment can significantly relieve the cancer pain of BALB/c nude rats， whose mechanism may be correlated with Ailitong Ointment in inhibiting tumor growth， decreasing NGF and TNF-α contents and increasing β-EP levels.
〔Keywords〕 Ailitong Ointment; cancer pain; tumor necrosis factor alpha; spinal nerve growth factor; beta-endorphin; endothelin-1
癌性疼痛亦称癌痛，是恶性肿瘤患者最常见亦是最痛苦的症状之一，其中包括由肿瘤直接引起的疼痛(如肿瘤压迫，骨、神经、内脏、皮肤、软组织肿瘤浸润或转移等)、肿瘤治疗引起的疼痛及肿瘤诊断检测引起的疼痛等。据国际癌症研究中心(International Agency for Research on Cancer， IARC)统计，2018年全球有18 078 957新增癌症病例，每10万人群中每年约有237人[1]。癌痛是癌症患者常见的症状之一，有80%的晚期癌症患者存在癌痛，其中50%的患者为中、重度癌痛，严重影响着生活质量[2]。我国约25%新诊断的癌症患者、33%正在接受治疗的癌症患者以及75%的晚期肿瘤患者伴有不同程度的疼痛[3]。然而由于目前治疗方法的局限性和治疗所带来的不良反应，仍有20%～40%癌痛患者不能得到满意的镇痛治疗[4]，因此，积极寻找更安全有效的癌痛治疗方法具有重要的意义。癌理通膏是佛山市中医院肿瘤中心依据中医理论及多年临床治疗经验研制的院内中药新制剂，具有活血止痛、化瘀散结、攻毒抗癌之功效。在临床应用中观察到癌理通膏有较好的止痛疗效，但其作用机制有待进一步研究。本研究通过皮下注射Walker 256乳腺癌细胞的方法建立裸鼠癌痛模型，动态观察癌理通膏对裸鼠自发痛评分和肿瘤体积的影响，同时检测癌理通膏对肿瘤重量及脊髓神經生长因子(nerve growth factor， NGF)、肿瘤坏死因子-α(tumornecrosis factor alpha， TNF-α)、内皮素-1(endothelin-1， ET-1)和β-内啡肽(beta-endorphin， β-EP)表达的影响。, http://www.100md.com(陈学彰 田华琴 梁贵文 王斌 李宏良 叶伟琼)
〔关键词〕 癌理通膏;癌性疼痛;肿瘤坏死因子-α;神经生长因子;β-内啡肽;内皮素-1
〔中图分类号〕R285.6 〔文献标志码〕A 〔文章编号〕doi：10.3969/j.issn.1674-070X.2020.07.012
〔Abstract〕 Objective To observe the analgesic effects of external application with Ailitong Ointment on BALB/c nude mouse with cancer pain and its impact on tumor growth， spinal nerve growth factor (NGF)， tumor necrosis factor alpha (TNF-α)， endothelin-1 (ET-1) and beta-endorphin (β-EP) expressions. Methods Walker 256 breast cancer cells were hypodermically injected in lateral thigh of BALB/c nude rats to establish nude rat model of cancer pain. The changes of spontaneous pain scores， gross tumor volume in the Ailitong group and the model group were dynamically observed. Tumor tissues were stripped to compare the tumor weight in the 2 groups; RT-PCR was used to detect the changes of spinal NGF， TNF-α， ET-1 and β-EP levels. Results From day 7 to day 10， spontaneous pain scores in the Ailitong group were significantly lower than the model group (P<0.05); From day 3 to day 10， tumor volume in the Ailitong group was significantly smaller than model group (P<0.01). Compared with the model group， the tumor weight (P<0.01)， NGF levels (P<0.01) and TNF-α levels (P<0.05) in the Ailitong group were significantly decreased; β-EP levels were significantly increased (P<0.05); ET-1 levels between the 2 groups were not significantly different (P>0.05). Conclusion Ailitong Ointment can significantly relieve the cancer pain of BALB/c nude rats， whose mechanism may be correlated with Ailitong Ointment in inhibiting tumor growth， decreasing NGF and TNF-α contents and increasing β-EP levels.
〔Keywords〕 Ailitong Ointment; cancer pain; tumor necrosis factor alpha; spinal nerve growth factor; beta-endorphin; endothelin-1
癌性疼痛亦称癌痛，是恶性肿瘤患者最常见亦是最痛苦的症状之一，其中包括由肿瘤直接引起的疼痛(如肿瘤压迫，骨、神经、内脏、皮肤、软组织肿瘤浸润或转移等)、肿瘤治疗引起的疼痛及肿瘤诊断检测引起的疼痛等。据国际癌症研究中心(International Agency for Research on Cancer， IARC)统计，2018年全球有18 078 957新增癌症病例，每10万人群中每年约有237人[1]。癌痛是癌症患者常见的症状之一，有80%的晚期癌症患者存在癌痛，其中50%的患者为中、重度癌痛，严重影响着生活质量[2]。我国约25%新诊断的癌症患者、33%正在接受治疗的癌症患者以及75%的晚期肿瘤患者伴有不同程度的疼痛[3]。然而由于目前治疗方法的局限性和治疗所带来的不良反应，仍有20%～40%癌痛患者不能得到满意的镇痛治疗[4]，因此，积极寻找更安全有效的癌痛治疗方法具有重要的意义。癌理通膏是佛山市中医院肿瘤中心依据中医理论及多年临床治疗经验研制的院内中药新制剂，具有活血止痛、化瘀散结、攻毒抗癌之功效。在临床应用中观察到癌理通膏有较好的止痛疗效，但其作用机制有待进一步研究。本研究通过皮下注射Walker 256乳腺癌细胞的方法建立裸鼠癌痛模型，动态观察癌理通膏对裸鼠自发痛评分和肿瘤体积的影响，同时检测癌理通膏对肿瘤重量及脊髓神經生长因子(nerve growth factor， NGF)、肿瘤坏死因子-α(tumornecrosis factor alpha， TNF-α)、内皮素-1(endothelin-1， ET-1)和β-内啡肽(beta-endorphin， β-EP)表达的影响。, http://www.100md.com(陈学彰 田华琴 梁贵文 王斌 李宏良 叶伟琼)