蝙蝠蛾拟青霉Cs-4菌粉对H22荷瘤小鼠的抗肿瘤作用  

Anti-tumor Effect of Paecilomyces hepiali Cs-4 Fermentation Powder on H22 Tumor-Bearing Mice

作　　者：闫芳 李欣[1] 包海鹰[1] 裴宏岩 杨明 图力古尔[1] 李玉[1] YAN Fang;LI Xin;BAO Haiying;PEI Hongyan;YANG Ming;TOLGOR Bau;LI Yu(Key Laboratory of Medicinal Fungal Resources and Development and UtilizationJilin Agricultural University,Changchun,Jilin 130118,China;Jiangxi Guoyao Co.,Ltd.,Nanchang,Jiangxi 330052,China)

机构地区：[1]吉林农业大学药用菌物资源及开发利用重点研究室,吉林长春130118 [2]江西国药有限责任公司,江西南昌330052

出　　处：《食用菌学报》2020年第4期77-84,共8页Acta Edulis Fungi

基　　金：国家中药标准化项目(ZYBZH-C-JX-39)。

摘　　要：利用H22细胞移植性肿瘤小鼠模型,探讨蝙蝠蛾拟青霉(Paecilomyces hepiali)Cs-4菌粉对荷瘤小鼠的抗肿瘤作用。将小鼠随机分成空白组、模型组、阳性对照组(环磷酰胺)和蝙蝠蛾拟青霉Cs-4菌粉低(0.5 g·kg^-1·d^-1)、中(1 g·kg^-1·d^-1)、高剂量(2 g·kg^-1·d^-1)组,连续给药10 d后,计算抑瘤率和脏器指数。肿瘤组织切片HE染色观察细胞排序、细胞完整度、细胞核数量和坏死区域大小等情况,免疫组化染色后观察并记录阳性细胞数及染色强度。用酶联免疫试剂盒测定小鼠血清中IL-6、IFN-γ、TNF-α、VEGF、AST、BUN含量。结果表明:在实验范围内,随着Cs-4菌粉给药剂量的增加,抑瘤率逐渐增加,高剂量组的抑瘤率可达78.4%;Cs-4菌粉各给药组小鼠的脏器指数分别有不同程度的恢复;模型组小鼠肿瘤组织细胞排列整齐紧密,可见大量细胞核,且生长状态良好,Cs-4菌粉各给药组的肿瘤细胞出现不同程度的细胞扭曲变形、模糊不清等现象;Cs-4菌粉可使VEGF、P53、BCL-2抗体结合阳性细胞数量减少,BAX、Caspase-3抗体结合阳性细胞数量增加,可提高小鼠血清中IL-6、IFN-γ、TNF-α含量,降低VEGF、AST含量。研究结果说明,Cs-4菌粉对H22造模的荷瘤小鼠具有一定的抗肿瘤作用,并可减少肝肾损伤,其作用机制可能与增强机体免疫力和影响体内VEGF、P53、BCL-2、BAX、Caspase-3蛋白的表达有关。The H22-based hepatocellular carcinoma ascites mouse model was used to evaluate the antitumor activity of Paecilomyces hepiali Cs-4 fermentation powder.Mice were randomly divided equally into six groups as follows:blank group,model group,positive control group(cyclophosphamide),low dose(0.5 g·kg^-1·d^-1),medium dose(1 g·kg^-1·d^-1)and high dose(2 g·kg^-1·d^-1)of P.hepiali Cs-4 powder.Mice in both the blank and model groups were administered physiological saline by oral gavage for 10 d,and mice administered different doses of P.hepiali Cs-4 powder were also fed intragastrically for 10 d.Then tumor inhibition rates and viscera indices were calculated.Hematoxylin-eosin(HE)staining was used to observe cell arrangement,cell integrity,number of nuclei,and necrotic area size of tumor tissue.Immunohistochemical staining was used to measure number of positive cells and staining intensity.Contents of IL-6,IFN-γ,vascular endothelial growth factor(VEGF),TNF-α,aspartate aminotransferase(AST)and blood urea nitrogen(BUN)in mice serum were determined by ELISA.The results showed that tumor inhibition rate increased as the Cs-4 powder dose increased within the tested range.The tumor inhibition rate of mice in the high dose group was 78.4%.Compared with the model group,organ indices of mice administered Cs-4 powder were recovered to different extents.Tumor cells in the model group were neatly and tightly arranged,with a large number of nuclei visible and in good growth condition.In contrast,tumor cells in Cs-4 powder treated groups were deformed and blurred under HE staining.Cs-4 powder resulted in reduced number of positive cells bound to VEGF,P53 and BCL-2,increased number of positive cells bound to BAX and Caspase-3,increased IL-6,IFN-γand TNF-αin the serum,and decreased serum levels of VEGF and AST.These results suggested that P.hepiali Cs-4 powder acts against tumor cells and protects liver and kidney from leisions in H22 tumor-bearing mice through immunoregulation and expression of VEGF,P53,BCL-2,BAX and Caspase-3 i

关 键 词：抑瘤率 脏器指数 HE染色 免疫组化染色 细胞因子 谷草转氨酶 血尿素氮 

分 类 号：TQ460.1[化学工程—制药化工]