绝经期和生育期雌激素缺乏对小鼠免疫系统的影响

Impact of estradiol deficiency on immune system in young and aged mice

目的探讨绝经期和生育期雌激素(E_2)缺乏对小鼠免疫系统的影响。方法清洁级健康雌性C57BL/6小鼠100只,分为手术去卵巢组、药物去卵巢组、自然绝经组(3组实验组)及发情间期组(对照组),每组25只。经刀豆蛋白A(Con-A)刺激后,采用ELISA法检测血清免疫球蛋白(Ig)M、Ig G、Ig A和E2水平,流式细胞术检测各组CD4/CD8比值,RT-PCR法检测4组小鼠脾脏IL-2、IL-4、IL-5、IL-10 m RNA表达水平。结果 3组实验组小鼠血清E2、Ig M、Ig G水平均明显低于对照组,差异均有统计学意义(均P<0.01)。手术去卵巢组小鼠血清Ig M、Ig G和Ig A水平均低于药物去卵巢组和自然绝经组,差异均有统计学意义(均P<0.01)。自然绝经组CD4/CD8比值低于对照组,差异有统计学意义(P<0.01);手术去卵巢组、药物去卵巢组与对照组CD4/CD8比值比较差异均无统计学意义(均P>0.05)。3组实验组小鼠IL-2、IL-4、IL-5 m RNA表达水平均明显低于对照组,差异均有统计学意义(均P<0.01);各组小鼠IL-10 m RNA表达水平比较差异均无统计学意义(均P>0.05)。结论 Con-A刺激后E_2缺乏状态下年轻与老龄化小鼠之间细胞因子模式有所不同,E_2缺乏对IL-2、IL-4、IL-5和Ig水平有影响,而E2对IL-10水平作用有限。

Objective To investigate the effects of estrogen deficiency on immune system in young and aged mice.Methods One hundred healthy female C57BL/6 mice were divided into 4 groups with 25 in each group ： natural menopausal group , surgical ovariectomy group , medical ovariectomy and diestrus group （control）. Blood and spleen samples were collected from animals 4 h after injection of Con- A for stimulation, the serum estradiol （E2）, IgM, IgG, IgA levels were assessed using enzyme linked immunosorbent assay （ELISA）, CD4/CD8 ration was determined by flow cytometry. The mRNA expression levels of IL- 2, IL- 4, IL- 5 and IL- 10 in spleen cells were detected by reverse transcription- polymerase chain reaction （RT- PCR）.Results The serum E2 levels natural menopausal group , surgical ovariectomy group and medical ovariectomy were significantly lower than that in control group （all P〈0.01）. The IgM and IgG levels in above three groups were significantly lower than those in the control group （all P〈0.01）; the IgM, IgG and IgA levels were the lowest in surgical overiectomy group （all P〈0.01）. The ratio of CD4/CD8, in the natural menopause group was lower than that in the control group （P〈0.01）. There was no significant difference in the ratio of CD4/CD8 between the surgical Ovariectomy group , medical ovariectomy and diestrus group （both P 〉0.05 ）. The expression levels of IL- 2, IL- 4 and IL- 5 mRNA of the mouse spleen were increased in the three experimental groups compared to control group （all P〈0.01）, there was no significant difference in IL- 10 mRNA expression levels （P 〉0.05）.Conclusion The responses of immune system to Con- A stimulation are different between the young and aged mice with E2 deficiency.The E2 deficiency affects IL- 2, IL- 4, IL- 5 and immunoglobulin levels , while has limited effect on IL- 10 levels in mice.