秀珍菇粉对H22荷瘤小鼠体内抗肿瘤作用研究

Anti-tumor activities of Pleurotus geesteranus fruit body powder on H22 tumor-bearing mice

目的本试验旨在研究秀珍菇抗肿瘤作用及其抑瘤机制。方法选用ICR雄性小鼠60只,取10只作为空白组,剩余50只小鼠通过腋部皮下接种H22小鼠腹水构建荷瘤小鼠模型,造模后随机分为模型组、阳性药(CTX)组、秀珍菇低、中、高剂量组,每组10只。模型组小鼠灌服生理盐水,阳性药组小鼠按20 mg/kg体重隔天腹腔注射注射环磷酰胺(CTX)生理盐水溶液,秀珍菇低、中、高剂量组小鼠分别按750、1500、3000 mg/kg体重每天剂量灌服秀珍菇生理盐水混悬液。给药10 d后,测定各组小鼠平均瘤重,肿瘤抑制率;测定免疫器官脏器指数、血清免疫球蛋白和细胞因子含量;测定肝、肾抗氧化指标;观察肿瘤和脾组织HE染色病理切片。结果(1)CTX及秀珍菇低、中、高剂量组小鼠的平均瘤重均极显著低于模型组(P<0.01),四组小鼠肿瘤抑制率分别为55.18%,29.06%、47.47%和48.80%。(2)与空白组比较,模型组小鼠脾指数、血清IgA和TNF-α含量及肝MDA含量显著升高(P<0.05,P<0.01),血清IL-6含量有上升趋势(P>0.05),而血清IL-2含量、肝CAT和GSH-Px活性及肾SOD、GSH-Px和CAT活性显著降低(P<0.05,P<0.01);同时,CTX组小鼠胸腺指数显著低于空白组(P<0.05)。(3)秀珍菇对荷瘤小鼠免疫和抗氧化功能异常改变具有逆转作用:与模型组比较,秀珍菇各剂量组小鼠血清IgA和TNF-α含量及高剂量组小鼠IL-6水平显著降低(P<0.05,P<0.01),低剂量组小鼠血清IL-2水平显著升高(P<0.01);秀珍菇处理还显著提高了各剂量组荷瘤小鼠肝CAT活性及肾SOD和CAT活性(P<0.05,P<0.01),显著升高中、高剂量组肝GSH-Px活性和低、中剂量组肾GSH-Px活性(P<0.05,P<0.01),并显著降低中剂量组的肝MDA含量(P<0.05)。(4)与CTX组比较,秀珍菇高剂量组小鼠脾指数显著提高(P<0.05),而血清IL-6水平显著降低(P<0.05)。(5)肿瘤组织病理切片显示CTX组和秀珍菇各剂量组的肿瘤坏死面积明显增加。结论秀珍菇可抑制H22实体移植瘤生长,其机制与其具有较强的免疫调节和抗氧化作用有关。

Objective To investigate the anti-tumor effects and mechanism of Pleurotus geesteranus powder(PGP)on H22 tumor-bearing mice.Methods The mouse tumor-bearing model was established by subcutaneous injection of ascites of H22 hepatocellular carcinoma into mice via the axilla.Sixty male ICR mice were randomly divided into one blank control(C)and five H22 tumor-bearing groups including tumor model control,positive control(cyclophosphamide,CTX)and three PGP groups.The mice in the model control group received 0.9%saline solution by oral gavage,the mice in the positive control group were intra-abdominally injected with CTX saline solution(20 mg/kg body weight every other day),and mice in the PGP-treated groups were administered PGP(dispersed in 0.9%saline solution)at low(750 mg/kg body weight,PGP-L),mid(1500 mg/kg body weight,PGP-M)and high(3000 mg/kg body weight,PGP-H)doses per day.The administration cycle was 10 d.When the trial was finished,the mean tumor weight,tumor inhibition rate and immune organ index were calculated,and the levels of serum immunoglobulins and cytokines,and antioxidant parameters in the liver and kidney were determined.Microscopic morphology of tumor and spleen tissues were observed by hematoxylin and eosin(HE)staining.Results(1)The mean tumor weight in the CTX and three PGP groups was significantly decreased compared with the model control(P<0.01).The tumor inhibition rate in the CTX and three PGP groups(low,mid,high)were 55.18%,29.06%,47.47%,and 48.80%,respectively.(2)Compared with the blank control,the spleen index(P<0.01),levels of serum immunoglobulin A(IgA,P<0.01)and tumor necrosis factorα(TNF-α,P<0.05),and liver malondialdehyde(MDA,P<0.05)were increased in the model group,whereas serum interleukiN-2(IL-2)content(P<0.01),activities of liver catalase(CAT,P<0.01),glutathione peroxidase(GSH-Px,P<0.01),kidney superoxide dismutase(SOD,P<0.01),GSH-Px(P<0.05),and CAT(P<0.01)in the model group were significantly decreased.Furthermore,the serum IL-6 content in the model group tended to be increased(P>0.05).The thymus index in the CTX group was significantly higher than in the blank control(P<0.05).(3)Treatment with PGP reversed the above abnormal performance in the model control.Levels of IgA and TNF-αin the three PGP treated(low,mid,high)groups(IgA:P<0.01,P<0.01,P<0.01;TNFα:P<0.05,P<0.01,P<0.05),IL-6 levels in the PGP-H group(P<0.05),and liver MDA content in the PGP-M group(P<0.05)were lower than in the model control group.IL-2 levels in the PGP-L group(P<0.05),activities of liver CAT(P<0.05,P<0.05,P<0.01),kidney CAT(P<0.01,P<0.01,P<0.01)and kidney SOD(P<0.01,P<0.01,P<0.01)in three PGP-treated(low,mid,high)groups,liver GSH-Px in the PGP-M and PGP-H groups(P<0.05),and kidney GSH-Px in the PGP-L and PGP-M groups(P<0.01)were significantly higher than in the model control group.(4)Compared with the CTX group,the spleen index in the PGP-H group was increased,and IL-6 levels were decreased significantly(P<0.05).(5)Furthermore,compared with the model control group,increased necrotic areas of tumors in the CTX group and all PGP groups were observed by HE staining.Conclusions PGP might have anti-tumor effects related to its immunoregulatory and antioxidant functions.