加味四君子汤对增龄大鼠免疫系统的调节作用及其初步机制探讨

目的 观察中药复方制剂加味四君子汤对增龄大鼠免疫系统功能的调节作用,并对可能的作用机制行初步探讨. 方法 选取50只12月龄健康Wistar大鼠,雌雄各半,随机分为5组,即加味四君子汤(以下简称药物)低剂量组、中剂量组、高剂量组,阳性对照组、老年对照组,每组各10只；另选取10只3月龄的Wistar大鼠作为青年对照组.各组分别给予加味四君子汤1.6、3.2、6.4 g/(kg·d),六味地黄丸混悬液1.5 g/(kg·d),2ml蒸馏水灌胃,持续给药90d.称量大鼠体重后处死,观察试验大鼠的血清免疫球蛋白(IgG)水平；计算胸腺指教、脾脏指数；将胸腺和脾脏组织进行HE染色,光镜下观察组织形态学改变；用免疫组化法检测胸腺白介素-2(IL-2)的表达情况及脾脏肿瘤坏死因子-α(TNF-α)的表达情况. 结果 与青年对照组相比较,各组大鼠血清IgG、胸腺IL-2、胸腺和脾脏指数均显著降低(P＜0.01),脾脏TNF-α表达水平均明显升高(P＜0.01)；与老年对照组比较,药物组的IgG、胸腺IL-2、胸腺指数升高(P＜0.05或P＜0.01),脾脏TNF-α表达水平降低(P＜0.01).光镜下,药物组胸腺有不同程度的萎缩,胸腺组织被脂肪替代等病理变化程度降低,胸腺细胞分布较密,着色良好.脾脏的白髓分界欠清晰,白髓略微增多,中性粒细胞数量增多,淋巴细胞排列比较疏松. 结论 加味四君子汤通过细胞因子之间的相互调节作用,增加机体的体液免疫、控制机体的高炎性状态,从而延缓老龄大鼠的炎性免疫衰老.

The regulation and research of mechanism of Plus SiJunZi Decoction in immune system of the aging rat

Objective To observe the regulation function of traditional Chinese medicine Plus SiJunZi Decoction in the immune system of aging rats,and to discusse the mechanism.Methods Fifty Wistar rats(male 25 and female 25,12 months old)were randomly divided into 5 groups,low dose group,middle dose group,high dose group,positive control group and the elderly control group with 10 rats in each group.The animals in 5 groups received Plus SiJunZi Decoction at a dose of 1.6 g/(kg·d),3.2 g/(kg·d),6.4 g/(kg·d),and Liu Wei Di Huang Wan at a dose of 1.5 g/(kg·d),2 ml of distilled pour stomach.Another 10 healthy Wistar rats(3 months old) were used as young control group.All animals received the treatment for 90 days.Then the rats were sacrificed.The serum immunoglobulin(IgG) level was measured and the thymus index and spleen index was calculated.The expression of thymic interleukin-2(IL-2) and tumor necrosis factor α(TNF-α) in spleen was detected.The morphological changes under light microscope were observed.Results Compared with the young control group,the serum levels of IgG,the expression of IL-2 in thymus,thymus index and spleen index were significantly decreased(P<0.01),and the expression of TNF-α in spleen was significantly decreased(P<0.01) in the aged group.Compared with the elderly control group,the expression of IL-2 in thymus,thymus index and spleen index were significantly increased(P<0.05 or P<0.01),and the expression of TNF-α in spleen was significantly decreased(P<0.01) in the drug groups.The thymus of drug groups had varying degrees of atrophy and decreased degree of fat substitution.The cells of thymus showed dense distribution and good coloring.The boundaries of white pulp and red pulp of the spleens was less clear.The white pulp was increased slightly,and the number of neutrophils was increased.The lymphocytes arranged loosely.Conclusions Plus SiJunZi Decoction might increase the fluid immunity through controlling the regulation of cytokines,and delay the inflammatory immune senescence in aging rats.