癌痛方正丁醇提取物抑制癌性疼痛的分子机制  

Molecular Mechanism of n-Butanol Extracts of Aitongfang on Inhibiting Cancer Pain

作　　者：黄鹤归 徐慧 黄贺达 杨全伟[1] 黄小龙[3] 覃双来[2] 胡作为[2] HUANG Hegui;XU Hui;HUANG Heda;YANG Quanwei;HUANG Xiaolong;QIN Shuanglai;HU Zuowei(Department of Pharmacy,Wuhan First Hospital,Wuhan 430022,China;Department of Oncology,Wuhan First Hospital,Wuhan 430022,China;Department of Respiratory,Wuhan First Hospital,Wuhan 430022,China)

机构地区：[1]武汉市第一医院药学部,武汉430022 [2]武汉市第一医院肿瘤科,武汉430022 [3]武汉市第一医院呼吸内科,武汉430022

出　　处：《医药导报》2022年第1期12-16,共5页Herald of Medicine

基　　金：国家自然科学基金资助项目(81803646);湖北省自然科学基金资助项目(2018CFB326,2018CKB921);武汉市卫生计生委科研计划资助项目(WZ18C03,WX18Z33,WX18Q47);武汉中青年医学骨干人才培养工程第八批(武卫通[2020]55号)。

摘　　要：目的探讨癌痛方正丁醇提取物(BTE)对Lewis肺癌小鼠肿瘤细胞凋亡、增殖及降钙素基因相关肽(CGRP)/磷酸化环磷腺苷效应元件结合蛋白(p-CREB)信号通路的影响。方法以皮下注射肿瘤细胞的方法建立C57BL/6小鼠Lewis肺癌模型,共20只,随机分为模型对照组及BTE组,每组10只。模型对照组给予0.9%氯化钠溶液灌胃,BTE组给予BTE1.97 g·kg^(-1)·d^(-1)灌胃,连续14 d,处死动物,剥离肿瘤组织。检测两组肿瘤质量、体积改变,苏木精-伊红(HE)染色法分析肿瘤组织形态改变,免疫荧光法检测5-溴脱氧尿嘧啶核苷(BRDU)阳性细胞比例及TUNEL阳性细胞数比例,Western blotting法分析CGRP/p-CREB信号通路改变。结果模型对照组和BTE组肿瘤质量分别为(2.20±0.82),(1.38±0.41)g;体积分别为(3.34±1.35),(1.35±0.34)cm^(3)(均P<0.05)。BTE组肿瘤组织部分细胞肿胀及细胞核固缩,BRDU阳性细胞比例显著降低(P<0.01),TUNEL阳性细胞数比例显著升高(P<0.01),CGRP及p-CREB蛋白表达水平均显著降低(P<0.05,P<0.01)。结论BTE能抑制Lewis肺癌小鼠肿瘤细胞增殖,促进其凋亡,具有抗肿瘤及镇痛作用,其作用机制可能为抑制CGRP/p-CREB信号通路。Objective To investigate the effect of n-butanol extracts of Aitongfang(BTE)on apoptosis,proliferation and calcitonin gene related peptide(CGRP)/cAMP-response element binding protein(CREB)signal pathway in Lewis lung cancer mice.Methods A total of 20 C57BL/6 mice Lewis lung cancer mouse models were established by subcutaneous injection of tumor cells.They were randomly divided into model control group and BTE group,with 10 animals in each group.The BTE group was given 1.97 g·kg^(-1)·d^(-1) BTE by gavage,and the model control group was given 0.9%sodium chloride solution by gavage for 14 consecutive days.The animals were sacrificed and the tumor tissue was stripped.The tumor mass and volume changes of the two groups were detected.The HE staining was used to analyze the morphological changes of tumor tissues,and the ratio of BRDU positive cells and the ratio of TUNEL positive cells were detected by immunofluorescence,as well as the changes of CGRP/p-CREB signal pathway were analyzed by Western blotting.Results The tumor mass of model control group and BTE group were(2.20±0.82)and(1.38±0.41)g,respectively.The volumes were(3.34±1.35)and(1.35±0.34)cm^(3),respectively(all P<0.05).The tumor cells in the BTE group were swollen and the nucleus was pyknotic,at the same time,the ratio of BRDU positive cells was significantly reduced(P<0.01).The ratio of the number of TUNEL positive cells in the BTE group was increased significantly(P<0.01).Compared with the model control group,the expression of CGRP and p-CREB protein of the BTE group were decreased significantly(P<0.05,P<0.01).Conclusion The BTE could inhibit proliferation and increase apoptosis of cancer cell in Lewis lung carcinoma.The CGRP/p-CREB signal pathway may mediate the inhibitory effect of BTE on cancer pain.

关 键 词：癌痛方 肺癌 降钙素基因相关肽 癌性疼痛 

分 类 号：R285.5[医药卫生—中药学] R730.52[医药卫生—中医学]