自然铜、鹿衔草对肺癌骨转移模型裸鼠肿瘤组织ICAM-1、MMP-9及PTHrP表达的影响  

Effects of Pyrite and Pyrola Herb on ICAM-1, MMP-9 and PTHrP Expression in Bone Metastasis Model of Lung Cancer in Nude Mice

作　　者：林思思[1] 袁拯忠[1] LIN Sisi;YUAN Zhengzhong(Department of Traditional Chinese Medicine,The First Affiliated Hospital,Wenzhou Medical University,Wenzhou,Zhejiang province,325000,China)

机构地区：[1]浙江省温州市温州医科大学附属第一医院中医科

出　　处：《浙江中西医结合杂志》2019年第9期714-717,共4页Zhejiang Journal of Integrated Traditional Chinese and Western Medicine

基　　金：浙江省温州市科技计划项目(No.Y20170734)

摘　　要：目的探讨自然铜、鹿衔草在裸鼠肺癌骨转移过程中对细胞间黏附分子-1(ICAM-1)、基质金属蛋白酶-9(MMP-9)及甲状旁腺激素相关蛋白(PTHrP)表达水平的影响。方法50只BALB/c祼鼠以A549肺癌细胞建立肺癌胫骨局部骨转移模型。将模型鼠随机分为自然铜组、鹿衔草组、联合给药组、阳性对照组及模型对照组。自然铜组按6g/kg隔天灌胃自然铜混悬液;鹿衔草组按6g/kg隔天灌胃鹿衔草混悬液,联合给药组按6g/kg隔天灌胃自然铜和鹿衔草混合溶液,阳性对照组腹腔注射帕米磷酸二钠注射液;模型对照组给予生理盐水处理。3周后收集肿瘤组织标本,采用免疫组织化学法及实时荧光定量PCR法(qRT-PCR)检测ICAM-1、MMP-9、PTHrP蛋白及mRNA表达水平。结果自然铜组、鹿衔草组及联合给药组ICAM-1表达阳性细胞百分率分别为(35.2±1.1)%、(33.6±4.0)%、(38.3±4.6)%,MMP-9表达阳性细胞百分率为(59.2±0.7)%、(65.4±1.7)%、(67.7±1.7)%,均低于模型对照组[(90.2±0.7)%、(94.3±0.4)%,P均<0.01]及阳性对照组[(57.9±2.3)%、(76.7±2.4)%,P均<0.01];联合给药组PTHrP表达阳性细胞百分率(73.3±7.2)%,低于模型对照组[(85.9±3.6)%,P<0.05]。自然铜、鹿衔草及联合给药组ICAM-1 mRNA相对表达量分别为(10±0.5)×10^-2、(7.3±0.6)×10^-2、(6.6±1.1)×10^-2,MMP-9 mRNA相对表达量分别为(11.9±2.2)×10^-2、(21.7±5.1)×10^-2、(23.4±5.9)×10^-2,均低于模型对照组[(100.8±13.8)×10^-2、(100.3±9.0)×10^-2,P均<0.01]及阳性对照组[(20.4±3.2)×10^-2、(45.5±7.4)×10^-2,P<0.01,P<0.05];联合给药组PTHrP mRNA相对表达量为(74.7±17.1)×10^-2,低于模型对照组水平[(100.9±14.9)×10^-2,P<0.01]。结论自然铜、鹿衔草及其联合用药可能通过下调ICAM-1、MMP-9、PTHrP表达水平抑制裸鼠肺癌骨转移过程。Objective To investigate the effects of pyrite and pyrola herb on the expression of intercellular adhesion molecule-1(ICAM-1), matrix metalloproteinase-9(MMP-9) and parathyroid hormone-related protein(PTHrP) in bone metastasis of lung cancer in nude mice. Methods Fifty BALB/c nude mice were used to establish local tibial metastasis model of lung cancer with A549 lung cancer cells. The model mice were randomly divided into pyrite group, pyrola herb group, combined drug group, positive control group and model control group. Pyrite group, pyrola herb group and combined drug group were gavaged with pyrite suspension, pyrola suspension, and mixed solution by 6g/kg every other day, respectively. The positive control group was given pamidronate disodium injection intraperitoneally. The model control group was treated with normal saline. Tumor tissue samples were collected 3 weeks later, and the expression levels of ICAM-1, MMP-9, PTHrP protein and mRNA were detected by immunohistochemistry and real-time fluorescence quantitative PCR(qRT-PCR). Results The percentages of ICAM-1 positive cells in pyrite group, pyrola group and combined drug group were (35.2±1.1)%, (33.6±4.0)%, (38.3±4.6)%, respectively. The percentages of MMP-9 positive cells were (59.2±0.7)%, (65.4±1.7)%, (67.7±1.7)%, respectively. All of them were lower than those in the model control group[(90.2±0.7)%, (94.3±0.4)%, P<0.01, respectively] and the positive control group[(57.9±2.3)%, (76.7±2.4)%, P<0.01, respectively];For the percentages of PTHrP positive cells, the ratio was (73.3±7.2)% in combined drug group, lower than that in model control group[(85.9±3.6)%, P<0.05]. The relative expression of ICAM-1 mRNA in pyrite, pyrola and combined drug group were(10±0.5)×10^-2, (7.3±0.6)×10^-2 and (6.6±1.1)×10^-2, MMP-9 mRNA were (11.9±2.2)×10^-2, (21.7±5.1)×10^-2 and (23.4±5.9)×10^-2. All of them were lower than those in model control group[(100.8±13.8)×10^-2, (100.3±9.0)×10^-2, P<0.01, respectively], and in positive control group[(20.4

关 键 词：裸鼠 自然铜 鹿衔草 细胞间黏附分子-1 基质金属蛋白酶-9 甲状旁腺激素相关蛋白 

分 类 号：R28[医药卫生—中药学]