基于PI3K/Akt信号通路探讨黄芩苷调节复发性流产小鼠子宫母胎界面免疫状态的影响

Effects of Baicalin on Regulating Immune Status of Uterine Maternal and Fetal Interface in RSA Mice Based on PI3K/Akt Signaling Pathway

目的:探讨黄芩苷对复发性流产(RSA)小鼠子宫母胎界面免疫状态的影响。方法:80只SPF级雌性CBA/J小鼠,其中16只小鼠建立正常妊娠模型设为对照组,64只小鼠建立RSA模型。RSA模型小鼠随机分为模型组、黄芩苷低剂量组(给药剂量为25 mg/kg)、黄芩苷中剂量组(给药剂量为50 mg/kg)和黄芩苷高剂量组(给药剂量为100 mg/kg),各16只。黄芩苷各剂量组按5 mL/kg剂量灌胃,对照组和模型组灌胃等体积的生理盐水,每日灌胃1次,连续14 d。比较各组小鼠流产率、胚胎丢失率,CD4^(+)和CD8^(+)T淋巴细胞、白介素-10(IL-10)、白介素-4(IL-4)、γ干扰素(IFN-γ)、肿瘤坏死因子-α(TNF-α)水平以及磷脂酰肌醇3-激酶(PI3K)、磷酸化丝氨酸/苏氨酸激酶(p-Akt)蛋白表达差异。结果:与模型组比较,黄芩苷各剂量组小鼠流产率、胚胎丢失率以及CD8^(+)T淋巴细胞、TNF-α、IFN-γ水平均显著降低,CD4^(+)T淋巴细胞、CD4^(+)/CD8^(+)、IL-4、IL-10水平和PI3K、p-Akt蛋白表达均显著升高(P<0.05);流产率、胚胎丢失率及CD8^(+)T淋巴细胞、TNF-α、IFN-γ水平与黄芩苷呈剂量依赖性降低,CD4^(+)T淋巴细胞、CD4^(+)/CD8^(+)、IL-4、IL-10水平及PI3K、p-Akt蛋白表达与黄芩苷呈剂量依赖性升高(P<0.05)。结论:黄芩苷可有效降低流产率,增强子宫母胎界面免疫状态,促进正常妊娠,该作用可能与调控PI3K/Akt信号通路蛋白表达相关。

Objective:To investigate the influence of baicalin on the immune state of the uterine maternal and fetal interface in recurrent spontaneous abortion(RSA)mice.Methods:16 SPF pregnant mice were taken as the blank control,64 SPF mice were established RSA model and then randomly divided into the model group,the baicalin groups of low-dose(25 mg/kg),medium-dose(50 mg/kg)and high-dose(100 mg/kg),with 16 mice in each group.The baicalin groups were given baicalin saline solution by gavage at the dose of 5 mL/kg,and the rats in the control group and the model group were given equal volume of saline solution.After 14 days of intervention,the rate of abortion,the rate of embryonic loss,the levels of CD4^(+)and CD8^(+)T lymphocytes,interleukin-10(IL-10),interleukin-4(IL-4),interferon-γ(IFN-γ)and tumor necrosis factor-α(TNF-α),as well as the protein expressions of sphosphoinositide 3-kinase(PI3K)and phospho-serine/threonine kinase(p-Akt)were compared among the groups.Results:Compared with those in the model group,the rate of abortion,the rate of embryonic loss,and the levels of CD8^(+)T lymphocytes,TNF-αand IFN-γwere significantly decreased,whereas the levels of CD4^(+)T lymphocytes,CD4^(+)/CD8^(+),IL-4 and IL-10,as well as the protein expressions of PI3K and p-Akt were significantly increased in different doses of baicalin groups(P<0.05).The rate of abortion,the rate of embryonic loss,the levels of CD8^(+)T lymphocytes,TNF-α,IFN-γshowed a dose-dependent reduction with baicalin;the levels of CD4^(+)T lymphocytes,CD4^(+)/CD8^(+),IL-4 and IL-10,as well as the protein expressions of PI3K and p-Akt showed a dose-dependent increase with baicalin(P<0.05).Conclusion:Baicalin can effectively reduce the abortion rate,enhance the immune state of uterus maternal and fetal interface to promote normal pregnancy,which may be related to the regulation of PI3K/Akt signaling protein expression.