美洲大蠊多肽PAP-2对Balb/c小鼠肝癌原位移植瘤免疫微环境的影响  

Effect of Periplaneta Americana polypeptide PAP-2 on the immune microenvironment of Balb/c mice with epatocellular carcinoma in situ transplanted tumors

作　　者：吕长玲 杜华钰 周杰 彭芳 吴定宇 LÜ Chang-ling;DU Hua-yu;ZHOU Jie;PENG Fang;WU Ding-yu(College of Pharmacy,Dali University,Dali 671000,Yunnan Province,China;Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D,Dali University,Dali 671000,Yunnan Province,China;College of Life Science and Engineering,Southwest Jiaotong University,Chengdu 610031,Sichuan Province,China)

机构地区：[1]大理大学药学院,云南大理671000 [2]大理大学云南省昆虫生物医药研发重点实验室,云南大理671000 [3]西南交通大学生命科学与工程学院,四川成都610031

出　　处：《中国临床药理学杂志》2023年第7期994-998,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金资助项目(81560600)。

摘　　要：目的探讨美洲大蠊多肽PAP-2对肝癌免疫微环境的影响,及其作用机制。方法通过给昆明种小鼠注入H22细胞悬液构建Balb/c小鼠肝癌原位移植瘤模型,将原位移植瘤小鼠随机分为10组:模型组,5-氟尿嘧啶组(20 mg·kg^(-1)5-FU),美洲大蠊多肽PAP-2低、中、高剂量组(50、100、200 mg·kg^(-1)PAP-2),5-氟尿嘧啶(20 mg·kg^(-1)5-FU)+PAP-2低、中、高剂量组(50、100、200 mg·kg^(-1)PAP-2),美洲大蠊CⅡ-3组(200 mg·kg^(-1)CⅡ-3),脱脂膏组(200 mg·kg^(-1)脱脂膏),5-Fu组隔天给药1次,其余各药物组每天1次,腹腔注射。通过检测抑瘤率、胸腺指数及脾指数,检测肿瘤组织中γ干扰素(IFN-γ)、白细胞介素-4(IL-4)、肿瘤坏死因子(TNF-α)和IL-1β的表达水平,检测小鼠脾细胞中相关淋巴细胞的变化水平。结果模型组、5-氟尿嘧啶组、美洲大蠊多肽PAP-2高剂量组、5-FU+PAP-2高剂量组、美洲大蠊CⅡ-3组、脱脂膏组的瘤质量分别为(0.96±0.15)、(0.33±0.19)、(0.30±0.23)、(0.12±0.04)、(0.35±0.12)和(0.41±0.06)g,IL-1β含量分别为(18.93±2.68)、(28.88±1.14)、(23.20±2.79)、(24.47±1.79)、(21.65±3.09)和(21.25±2.78)pg·mL^(-1),TNF-α含量分别为(12.32±1.12)、(25.71±0.98)、(14.25±1.94)、(23.06±1.71)、(13.49±1.38)和(14.34±2.18)pg·mL^(-1),巨噬细胞比例分别为(0.94±0.64)%、(3.19±1.12)%、(3.13±1.15)%、(5.45±3.49)%、(2.03±0.59)%和(3.76±0.44)%,B细胞比例分别为(35.53±9.84)%、(61.30±2.57)%、(59.63±3.36)%、(47.20±12.61)%、(53.60±5.68)%和(54.88±4.48)%。模型组的上述指标与其余各组相比,差异均有统计学意义(均P<0.05)。结论美洲大蠊多肽PAP-2能够提高肝癌原位移植瘤小鼠的免疫功能,一定程度上改善其免疫微环境。Objective To investigate the effect and mechanism of action of Periplaneta Americana polypeptide PAP-2 on the immune microenvironment of hepatocellular carcinoma.Methods Balb/c mice were randomly divided into 10 groups:model group,5-Fu group(20 mg·kg^(-1)5-Fu),PAP-2-L,-M,-H group(50,100,200 mg·kg^(-1) Periplaneta Americana polypeptide PAP-2),5-Fu(20 mg·kg^(-1)5-Fu)+PAP-2-L,-M,-H group(50,100,200 mg·kg^(-1) PAP-2),CⅡ-3 group(200 mg·kg^(-1) Periplaneta Americana CII-3),and degreasing paste group(200 mg·kg^(-1) degreasing paste ) ,5 - Fu group every other day,the rest of the group once a day. All were administeredintraperitoneally. The tumor inhibition rate,thymus and spleen indices were measured,and the tumor tissues weretested for interferon - γ ( IFN - γ) ,interleukin - 4 ( IL - 4) ,tumor necrosis factor - α ( TNF - α) and IL - 1β. Theexpression levels of related lymphocytes in mouse spleen cells were examined. Results The tumor weights of the modelgroup,5 - Fu group,Periplaneta Americana polypeptide PAP - 2 - H group,5 - FU + PAP - 2 - H group,CⅡ - 3group and degreasing paste group were ( 0. 96 ± 0. 15 ) ,( 0. 33 ± 0. 19 ) ,( 0. 30 ± 0. 23 ) ,( 0. 12 ± 0. 04 ) ,( 0. 35 ± 0. 12) and ( 0. 41 ± 0. 06) g;IL - 1β levels were ( 18. 93 ± 2. 68) ,( 28. 88 ± 1. 14) ,( 23. 20 ± 2. 79) ,( 24. 47 ± 1. 79 ) ,( 21. 65 ± 3. 09 ) and ( 21. 25 ± 2. 78 ) pg·mL^(-1);TNF - α levels were ( 12. 32 ± 1. 12 ) ,( 25. 71 ± 0. 98) ,( 14. 25 ± 1. 94) ,( 23. 06 ± 1. 71) ,( 13. 49 ± 1. 38) and ( 14. 34 ± 2. 18) pg·mL^(-1);macrophageratios were ( 0. 94 ± 0. 64) %,( 3. 19 ± 1. 12) %,( 3. 13 ± 1. 15) %,( 5. 45 ± 3. 49) %,( 2. 03 ± 0. 59) % and( 3. 76 ± 0. 44) %;proportion of B cells were ( 35. 53 ± 9. 84 ) %,( 61. 30 ± 2. 57 ) %,( 59. 63 ± 3. 36 ) %,( 47. 20 ± 12. 61) %,( 53. 60 ± 5. 68) % and ( 54. 88 ± 4. 48) %. All remaining groups showed statistically significantdifferences compared to the model group ( P < 0. 05) . Conclusion The Periplaneta Americana polypeptide PAP - 2can enhance the immun

关 键 词：美洲大蠊多肽PAP-2 肝细胞癌 免疫微环境 原位移植瘤 

分 类 号：R28[医药卫生—中药学]