不同证候小鼠肾上腺皮质激素与细胞因子表达的关系

The Correlation between Adrenal Corticosteroids and Cytokines Expressions in Mice of Different Syndromes

目的研究细胞因子在不同证候小鼠肾上腺中的表达及其与血清皮质激素的关系。方法采用实验小鼠及其标准化四诊及辨证方法,对60只正常小鼠与190只H22肝癌荷瘤小鼠予以辨证分型,用ELISA方法检测血清皮质酮、醛固酮含量,以及实时荧光定量PCR技术检测肾上腺细胞因子表达。结果获得正常无证、正常气盛证、正常气虚证小鼠,以及邪毒壅盛证、邪毒居中证、邪毒微弱证、邪毒气虚证荷瘤小鼠。荷瘤小鼠血清皮质激素显著高于正常小鼠(P<0.05),荷瘤小鼠4个证候组间,以邪毒壅盛证升高最显著(P<0.05)。相对于正常小鼠而言,白细胞介素(IL)-1β、IL-2、IL-6、IL-10、IL-12α、IL-12β和肿瘤坏死因子-α(TNF-α)等细胞因子在荷瘤小鼠不同证候中表达升高,仅IL-1α和IL-5在荷瘤小鼠中表达下降,而IL-13和转化生长因子-β1(TGF-β1)表达呈无规律性。其中IL-4与干扰素-α(INF-α)在正常与荷瘤小鼠肾上腺中均未检测到其表达。值得注意的是,邪毒程度越严重者,皮质酮与醛固酮水平及IL-6表达越高,而IL-1β、IL-2、IL-5、IL-12α、IL-12β、TNF-α表达越低。结论荷瘤小鼠血清皮质激素水平升高可能是在肿瘤慢性应激诱导下,部分细胞因子参与肾上腺皮质激素的合成与分泌,其中IL-6可能正向调控邪毒证荷瘤小鼠皮质激素分泌,而IL-1β、IL-2、IL-5、IL-12α、IL-12β、TNF-α则可能起到负性调控作用。

ABSTRACT Objective To study the cytokines expressions in the adrenal gland and its correlation with ser- um adrenal corticosteroids in mice of different syndromes. Methods Using the quantitative four diagnosis and syndrome differentiation methods, 60 normal mice and 190 H22 liver cancer bearing mice were syndrome typed. Serum corticosterone and aldosterone were tested by ELISA, and mRNA expressions of cytokines in the adrenal gland were detected using Real-time PCR. Results Mice of different syndromes were obtained, such as normal mice of no syndrome, normal mice of vigorous qi syndrome, normal mice of qi deficiency syndrome, liver cancer bearing mice of excessive evil toxic syndrome, liver cancer bearing mice of evil lying in the middle syndrome, liver cancer bearing mice of weak evil toxic syndrome, and liver cancer bearing mice of poisonous pathogenic factors and qi deficiency syndrome. The serum corticosteroids were significantly higher in the liver cancer bearing mice than in the normal mice （P 〈0.05）. The cortex hormones increased most significantly in the liver cancer bearing mice of excessive evil toxic syndrome （P 〈0.05）. Compared with the normal mice, IL-I~, IL-2, IL-6, IL-10, IL- 12~, IL-1213, and TNF-a gene expressions increased in the liver cancer bearing mice, while only expressions of IL-1 a and IL-5 decreased. But the expressions of IL-13 and transforming growth factor ~1 （TGF-~I） showed no regularity. The expressions of IL-4 and INF-a were not detected in all mice. It is notable that the more severe de- gree of poisonous pathogenic factors, the higher the expressions of serum corticosterone and aldosterone levels as well as IL-6, the lower expressions of IL-I~, IL-2, IL-5, IL-12cc, IL-1215, and TNF-a. Conclusions The in- creased serum corticosteroid level in liver cancer bearing mice could possibly be induced by chronic tumor stress, partial cytokines were involved in the synthesis and secretion of the adrenal hormone. Of them, IL-6 might positively regulate the secretion of corticosteroids, while IL-lJ3, IL-2, IL-5, IL-12a, IL-1213, and TNF-a might negativelv reaulate their secretions.