氢化可的松诱发虚证状态对H22肝癌小鼠肿瘤增长的影响

目的?研究氢化可的松诱发的虚证状态对肝癌小鼠肿瘤增长的影响。方法?将雄性昆明种小鼠随机分为正常对照组、肿瘤模型组、氢化可的松组，氢化可的松肿瘤组，采用氢化可的松给药小鼠14?d造成虚证状态，给药第1天同步接种H22肝癌细胞至腋下复制荷瘤小鼠模型。动态观测小鼠体质量与肿瘤大小变化；处死小鼠后，取脾脏、胸腺称质量并计算脏器指数；采用实时荧光定量PCR技术检测肾上腺类固醇合成酶以及肿瘤增殖相关的mRNA表达；运用Western blot方法检测肿瘤Akt、p-Akt蛋白表达。结果?与正常对照组比较，肿瘤模型组脾脏显著增大（P＜0.05），肾上腺Cyp11a1、Cyp11b1、Cyp11b2的基因表达显著下调（P＜0.05）；使用氢化可的松的小鼠脾脏和胸腺明显萎缩（P＜0.01），肾上腺Star、Cyp11a1、Cyp21a1、Cyp11b1基因均下调（P＜0.05）。与肿瘤模型组比较，氢化可的松肿瘤组小鼠接种肿瘤第7天肿瘤体积减小（P＜0.05），同时氢化可的松显著抑制肿瘤组织Akt1基因表达（P＜0.05），促使Foxo3基因表达上调（P＜0.05）、抑制Akt、p-Akt蛋白表达。与氢化可的松组比较，氢化可的松肿瘤组小鼠脾脏、胸腺萎缩减轻，肾上腺类固醇合成酶基因表达均上调（P＜0.05）。结论?氢化可的松通过抑制内分泌免疫功能诱发小鼠虚证，短期使用小鼠肿瘤增殖减缓，而持续性虚损状态下促进肿瘤生长。 

The Effect of Hydrocortisone Induced Deficiency Syndrome on Tumor Growth in H22 Liver Cancer Mice

OBJECTIVE?To study the effect of hydrocortisone induced deficiency syndrome on tumor growth in H22 liver cancer mice. METHODS?Kunming male mice were randomly divided into normal control group， tumor model group，hydrocortisone group， and hydrocortisone tumor group. Mice were given hydrocortisone for 14?d， and H22 liver cancer cells were inoculated simultaneously under the axilla to replicate the liver cancer mice model on the first day of hydrocortisone administration. The mice body mass and tumor size were observed. The mice were executed， and the spleen and thymus were weighed and the organic index were calculated. Then， mRNA expression of adrenal steroid synthase genes and tumor growth associated genes were detected by qPCR. Akt and p-Akt protein expression were assayed by Western blot. RESULTS?Compared with normal control group， the spleen of tumor model group increased significantly (P<0.05). The gene expression of Cyp11a1，Cyp11b1 and Cyp11b2 significantly reduced (P<0.05). The spleen and thymus of the two hydrocortisone groups significantly decreased (P<0.01)， and Star， Cyp11a1， Cyp21a1 and Cyp11b1 of adrenal all down-regulated (P<0.05). Compared with the tumor model group， tumor tissue of hydrocortisone tumor mice was smaller in 7th day (P<0.05). At the same time， the hydrocortisone inhibited Akt1 expression in tumor tissue (P<0.05)， prompted Foxo3 expression (P<0.05)， inhibited Akt and p-Akt protein expression. Compared with the hydrocortisone group， the atrophy of spleen and thymus alleviated and adrenal steroid synthase genes all up-regulated (P<0.05) in the hydrocortisone tumor groups. CONCLUSION?Hydrocortisone can induce the deficiency syndrome in mice by inhibiting the endocrine immune function， the proliferation of tumor reduce in early stage， while tumor growth going up in persistent deficiency syndrome mice.