玉郎伞多糖对S_(180)荷瘤小鼠氧化应激、免疫调节及血管生成的影响

Effects of Yulangsan polysaccharide on oxidative stress,immune regulation and angiogenesis in S_(180)tumor-bearing mice

目的探讨玉郎伞多糖(Yulangsan polysaccharides,YLSPS)对S_(180)荷瘤小鼠的体内抗肿瘤作用及其机制。方法以昆明小鼠建立S_(180)皮下移植瘤模型,随机分为模型组、环磷酰胺(cyclophosphamide,CTX 20 mg·kg^(-1)·d^(-1))组、YLSPS低,中,高剂量(150、300、600 mg·kg^(-1)·d^(-1))组,连续给药8 d后处死小鼠,检测小鼠瘤体质量、抑瘤率及其脏器指数;通过HE染色观察小鼠移植瘤细胞的形态学特征;测定血清中超氧化物歧化酶(superoxide dismutase,SOD)、谷胱甘肽过氧化物(glutathione peroxidase,GSH-PX)活性,丙二醛(malondialdehyde,MDA)及过氧化氢酶(catalase,CAT)的含量;采用ELISA法测定小鼠血清中血管内皮生长因子(vascular endothelial growth factor,VEGF)的含量;免疫组织化学法检测药物对微血管密度(microvascular density,MVD)表达的影响。结果与模型组比较,YLSPS(300、600 mg·kg^(-1)·d^(-1))可显著抑制S_(180)荷瘤小鼠的肿瘤生长,提高小鼠脾脏指数和胸腺指数(P<0.05或P<0.001);移植瘤HE染色表明,相较于模型组,经YLSPS干预后肿瘤细胞异型性降低,病理性核分裂减少,可见散在及融合成片状的坏死灶;血清生化指标显示YLSPS(300、600 mg·kg^(-1)·d^(-1))能够明显升高血清GSH-Px、CAT和SOD水平,降低血清MDA及VEGF水平(P<0.05或P<0.001);ELISA法与免疫组织化学法表明YLSPS(300、600 mg·kg^(-1)·d^(-1))可显著抑制VEGF、MVD的表达(P<0.05或P<0.001)。结论YLSPS可抑制荷瘤小鼠肿瘤的生长,其机制可能与增强小鼠免疫功能、抗氧化作用及抑制S_(180)肿瘤组织中VEGF与MVD的表达有关。

Objective To investigate in vivo anti-tumor effects and mechanism of Yulangsan polysaccharide(YLSPS)on S_(180) tumor-bearing mice.Methods The S_(180) subcutaneous transplanted tumor model was established by Kunming mice.All mice were randomly divided into model group,cyclophosphamide(CTX 20 mg·kg^(-1)·d^(-1))group,YLSPS low,medium and high dosage(150,300 and 600 mg·kg^(-1)·d^(-1))groups,and they were sacrificed after 8 d of continuous administration.The tumor weights,tumor inhibition rates and organ indexes were measured;morphological characteristics of transplanted tumor cells were identified by HE staining;the activity of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),the activity of malondialdehyde(MDA)and catalase(CAT)in serum were checked;the content of vascular endothelial growth factor(VEGF)in mice serum was determined by ELISA;drug effects on microvascular density(MVD)expression were detected by immunohistochemistry.Results Compared with the model group,YLSPS(300,600 mg·kg^(-1)·d^(-1))significantly inhibited the tumor growth of S_(180)tumor-bearing mice and increased the spleen index and thymus index(P<0.05 or P<0.001).Compared with the model group,HE staining indicated that tumor cell atypia and pathologic karyokinesis decreased after YLSPS intervention;diffused and flaked necrotic foci were observed.Serum biochemical index showed that YLSPS(300,600 mg·kg^(-1)·d^(-1))could significantly increase serum GSH-Px,CAT and SOD levels and decrease serum MDA and VEGF levels(P<0.05 or P<0.001);ELISA and immunohistochemistry indicated that YLSPS(300,600 mg·kg^(-1)·d^(-1))could significantly inhibit the expression of VEGF and MVD(P<0.05 or P<0.001).Conclusion YLSPS could inhibit the tumor growth in S_(180)tumor-bearing mice,and the mechanism may be related to enhancing immune function and anti-oxidation,and inhibiting the expression of VEGF and MVD in S_(180)tumor tissues.