目的 探讨车叶草苷对小鼠Lewis肺癌种植瘤的抑瘤和抗炎作用。方法 SPF级小鼠36只,制备荷瘤小鼠模型,然后将成瘤小鼠随机分为模型对照组、车叶草苷组、顺铂对照组。分别施加经口灌服车叶草苷或腹腔注射顺铂等干预因素,1次/d,连续3周。末次给药后,测量小鼠体质量、瘤体质量,检测血清中IL-1β、TNF-α含量;检测瘤组织中TLR4、MYD88、NF-κB的表达水平;检测瘤组织中p-NF-κB的表达定位及水平。结果 与模型对照组比较,车叶草苷组和顺铂对照组小鼠血清IL-1β、TNF-α含量显著降低,差异有统计学意义(P<0.01);车叶草苷组和顺铂对照组比较无统计学差异。与模型对照组比较,车叶草苷组和顺铂对照组小鼠瘤组织中TLR4、MYD88、NF-κB表达水平显著降低,差异有统计学意义(P<0.01);车叶草苷组和顺铂对照组比较无统计学差异。与模型对照组(0.261±0.026)比较,车叶草苷组(0.171±0.026)和顺铂对照组(0.207±0.020)小鼠瘤组织中p-NF-κB表达水平显著降低,差异有统计学意义(P<0.01);车叶草苷组和顺铂对照组比较无统计学差异。结论 车叶草苷对Lewis荷瘤鼠具有明显的抑瘤作用,能够降低荷瘤小鼠整体的炎性反应状态。
Abstract
Objective To observe the anti-tumor and anti-inflammatory effect of asperuloside on mice with Lewis lung cancer, and to investigate the anti-inflammatory mechanism by which asperuloside inhibits the overactive tlr4/myd88/nf-κb pathway. Methods Thirty-six healthy c57bl/6j mice of SPF grade, after one week of adaptive feeding, underwent subcutaneous injection of Lewis cells under the armpits to establish a tumor-bearing model before they were randomly divided into the model control group, asperuloside group and cisplatin control group. Corresponding intervention was implemented, such as orally taking asperuloside or intraperitoneal injection of cisplatin, once a day for 3 weeks. After the last dose, the health status of these mice was observed, body mass and tumor mass measured, and their peripheral blood was collected. Levels of il-1β and tnf-α in serum were detected by ELISA. The expression levels of tlr4, myd88 and nf-κb in tumor tissues were measured with Western-blot technology. The localization and level of p-nf-κb in tumor tissues were measured by immunohistochemical technology. Results There was no significant difference in body weight between the three groups before administration. After administration, the weight of mice in the asperuloside group increased (P<0.01) compared with the model control group, and the difference was statistically significant. Compared with the asperuloside group, the weight of mice in the cisplatin control group was reduced (P<0.01) and the difference was also statistically significant. Compared with the model control group, the tumor index of mice in the asperuloside group and cisplatin control group was reduced (P< 0.01), and the difference was statistically significant. Compared with the model control group, the serum contents of il-1β and tnf-α were decreased(P<0.01), so were the expression levels of tlr4, myd 88, nf-κb and p- nf-κb in tumor tissues (P<0.01), and the difference was statistically significant. Conclusions Asperuloside can reduce inflammatory response in Lewis tumor- bearing mice.
关键词
车叶草苷 /
Lewis肺癌 /
抗炎 /
TLR4/MYD88/NF-κB信号通路
Key words
asperuloside /
Lewis lung cancer /
anti-inflammatory /
tlr4/myd88/nf-κb signaling pathway
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] 洪 庆,徐曼丽,汤 建.车叶草苷的研究进展[J].中国野生植物资源,2018,37(4):43-45.
[2] Yinghan Chan,Sin Wi,Joycelin Zhu, et al. Emerging therapeutic potential of the iridoid molecule, asperuloside: a snapshot of its underlying molecular mechanisms[J]. Chem Biol Interact,2020,315(5):1-10.
[3] Liao Y,Xu L,Lin X,et al.Temporal trend in lung cancer burden attributed to ambient fine particulate matter in Guangzhou,China[J].Biomed Environ Sci,2017,30(10):708-717.
[4] Sigismund S,Avanzato D,Lanzetti L.Emerging functions of the EGFR in cancer[J].Mol Oncol,2018,12(1):3-20.
[5] Gazdar A F,Bunn P A,Minna J D.Small-cell lung cancer:what we know,what we need to know and the path forward[J].Nat Rev Cancer,2017,17(12): 725-737.
[6] 李红霞,杨 磊,陈小丽,等.鸡矢藤环烯醚萜苷体外抗肿瘤活性研究[J].中国药师,2017,20(12):2117-2122.
[7] 冯 原,江 颖,周 颖,等.补肺化瘀汤对气虚血瘀证Lewis肺癌小鼠的影响[J].中成药,2019,41(11):2625-2631.
[8] He Jingyu,Lu Xianyuan,Wei Ting, et al. Asperuloside and asperulosidic acid exert an anti-inflammatory effect via suppression of the NF-κB and MAPK signaling pathways in LPS-Induced RAW 264.7 macrophages[J]. Int J Mol Sci, 2018,19(2027):1-12.
[9] Qiu Jiaming,Chi Gefu,Wu Qianchao, et al.Pretreatment with the compound asperuloside decreases acute lung injury via inhibiting MAPK and NF-κB signaling in a murine model[J]. Int Immunopharmacol,2016,31(2):109-115.
[10] 程建超,张星星,童佳兵,等.芪玉三龙汤对肺癌小鼠肿瘤组织TLR4/MyD88/NF-κB通路分子表达的影响[J].中药药理与临床,2019,35(5):101-106.
[11] 杨 静,周 颖,金咏梅,等.胰腺癌患者循环肿瘤细胞及TLR4、TLR9、myd88的表达水平与其化疗效果及转移、复发的关系[J].现代生物医学进展,2017,17(28):5524-5527.
[12] 程建超,张星星,童佳兵,等.芪玉三龙汤对肺癌小鼠肿瘤组织TLR4/MyD88/NF-κB通路分子表达的影响[J].中药药理与临床,2019,35(5):101-106.
[13] Zhou J,Deng Y,Li F,et al.Icariside Ⅱ attenuates lipopolysaccharide-induced neuroinflammation through inhibiting TLR4/MyD88/NF-κB pathway in rats[J].Biomed Pharmacother,2019,11(3):315-324.