猫棒束孢联合环磷酰胺对H22荷瘤小鼠的治疗作用

Therapeutic effects of Isaria felina combined with cyclophosphamidein hepatoma H22 tumor-bearing mice

目的 研究冬虫夏草来源的猫棒束孢(Isaria felina,IF)联合环磷酰胺(cyclophosphamide, CTX)对肝癌H22荷瘤小鼠的治疗作用。方法 建立H22荷瘤小鼠模型,随机分组,设正常对照组(NC group,蒸馏水)、模型对照组(MC group,蒸馏水)、CTX组(CTX group, 25 mg/kg)、IF组(IF group, 400 mg/kg)和IF+CTX组(IF+CTX group, IF 400 mg/kg+CTX 25 mg/kg),每组5只小鼠;蒸馏水、IF灌胃给药,CTX腹腔注射给药,连续给药10 d。实验结束后,计算各组小鼠平均肿瘤体积和瘤重、抑瘤率、q值、免疫器官脏器指数;检测血常规和血清细胞因子含量;观察肿瘤组织苏木精-伊红(HE)染色病理形态变化。结果 各给药组小鼠的肿瘤体积和重量均显著低于MC组(P<0.05)。CTX组、IF组、IF+CTX组小鼠的抑瘤率分别为49.3%、34.2%、72.8%,q值为1.09。IF+CTX组白细胞(WBC)、淋巴细胞(Lymph)、血小板(PLT)数量显著高于CTX组(P<0.05)。MC组小鼠的脾指数显著高于NC组,IF+CTX组小鼠脾指数显著低于MC组(P<0.05)。MC组小鼠的血清IFN-γ水平显著低于NC组,IF组和IF+CTX组的IFN-γ水平显著高于MC组和CTX组(P<0.05)。MC组肿瘤细胞生长状态良好,数量多,排列紧密;CTX组、IF组和IF+CTX组肿瘤组织可见肿瘤细胞排列松散,多处肿瘤细胞灶性坏死,坏死细胞核固缩碎裂。结论 IF和CTX联用对H22荷瘤小鼠有相加的抑瘤作用,可减轻小鼠的免疫功能抑制,具有免疫调节功能。

Objective To investigate the therapeutic effects of Isaria felina derived from Cordyceps sinensis combined with cyclophosphamide(CTX)in hepatoma H22 tumor-bearing mice.Methods An H22 tumor-bearing mouse model was established and mice were divided randomly into a normal control group(NC group,distilled water),model control group(MC group,distilled water),positive control group(CTX group,25 mg/kg),Isaria felina group(IF group,400 mg/kg),and combined administration group(IF+CTX group,IF 400 mg/kg+CTX 25 mg/kg),with 5 mice in each group.Distilled water and IF were administered by gavage,and CTX was administered by intraperitoneal injection.The administration cycle was 10 days.At the end of the experiment,the mean tumor volume and weight,tumor inhibition rate,q value,and immune organ index were calculated,and routine blood indexes and cytokine levels were determined.Histopathological changes in tumor tissues were observed by HE staining.Results The tumor volume and mass were significantly lower in mice in each treatment group compared with those in mice in the MC group(P<0.05).The tumor inhibition rates in the CTX,IF,and IF+CTX groups were 49.3%,34.2%,and 72.8%,respectively,and the q value was 1.09.The numbers of white blood cells,Lymph,and platelets were significantly higher in the IF+CTX group than in the CTX group(P<0.05).The spleen index was significantly higher in the MC group compared with that in the NC group,and significantly lower in the IF+CTX group compared with that in the MC group(P<0.05).Serum interferon-γlevels were significantly lower in the MC group than in the NC group,and were significantly higher in the IF and IF+CTX groups compared with those in the MC and CTX groups(P<0.05).Pathologically,tumor cells in the MC group grew well and were numerous and closely arranged,while cells in the CTX,IF,and IF+CTX groups were arranged loosely,with focal necrosis and nuclear pyknosis of necrotic cells in many places.Conclusions The combination of IF and CTX has an additive anti-tumor effect on H22 tumor-bearing mice,which can alleviate immunosuppression and have an immunomodulatory function.