酪酸梭菌双岐杆菌二联活菌对早产小鼠CD4^+ T细胞CD28和PD1表达的影响及意义

Effect and significance of Changlekang on CD28 and PD1 expression of CD4^+ T cells in premature mice

目的:探讨酪酸梭菌双歧杆菌二联活菌对CD28和程序性死亡分子1(PD1;CD279)在早产小鼠CD4^+T细胞表达的影响及意义。方法:用米非司酮(RU486)腹腔注射无菌孕鼠建立早产模型。随机选择出生后第1天(postnatal day 1,P1)的小鼠分为早产实验组(Ⅰ组)、早产对照组(Ⅱ组)和足月对照组(Ⅲ组),每组各16只。Ⅰ组与Ⅱ组为早产模型所生幼鼠,Ⅲ组为未进行干预的孕鼠自然分娩的幼鼠。Ⅰ组给予酪酸梭菌双岐杆菌二联活菌灌胃,同一时间给予Ⅱ组与Ⅲ组等量生理盐水灌胃。3组新生鼠分别在P14、P21,用流式细胞术检测CD4^+T细胞表面CD28及PD1表达量。结果:相对于Ⅲ组,Ⅱ组在P14时,CD4^+T细胞表面CD28及PD1的表达没有显著变化(P>0.05),但在P21时,两分子的表达均增高(P<0.05);相对于Ⅱ组或Ⅲ组,在P14和P21时,Ⅰ组CD28及PD1的表达均升高(P<0.05);相对于P14,在P21时,Ⅱ组CD28的表达更高(P<0.05),但Ⅰ组和Ⅲ组均无显著变化(P>0.05);相对于P14,在P21时,Ⅱ组PD1的表达增强(P<0.05),而Ⅰ组PD1的表达降低(P<0.05),Ⅲ组PD1的表达差异无统计学意义(P>0.05)。结论:早产小鼠CD4^+T细胞表面CD28和PD1表达异常;酪酸梭菌双岐杆菌二联活菌可能通过调节早产小鼠CD28和PD1的表达,促进CD4^+T细胞的成熟与活化,进而增强早产小鼠的免疫功能。

Objective:To investigate the effect of Changlekang(live clostridium butyricum and bifidobacterium)on the expression of CD28 and PD1 on CD4^+T cells in premature mice.Methods:Sterile mouse models of preterm birth were established by intraperitoneal injection of mifepristone.Male and female mice were randomly selected on the postnatal day 1(P1),and divided into preterm birth group(groupⅠ),preterm control group(groupⅡ)and full-term control group(groupⅢ)(n=16 in each group).The mice in groupⅠand groupⅡwere premature,and those in groupⅢwere spontaneous birth.Mice in groupⅠwere intragastrically administered with Changlekang,and those in groupⅡandⅢwere intragastrically treated with equivalent amount of saline.The expression of CD28 and PD1 on the surface of CD4^+T cells was detected by flow cytometry on P14 and P21,respectively for the three groups of mice.Results:Compared with groupⅢ,CD28 and PD1 expression on the surface of CD4^+T cells did not change significantly in groupⅡat P14(P>0.05),yet was significantly increased at P21(P<0.05).Notably increased CD28 and PD1 expression was seen in groupⅠat P14 and P21(P<0.05).The expression of CD28 was much higher at P21 than at P14 for groupⅡ(P<0.05),whereas remained almost unchanged for groupⅠandⅢ(P>0.05).PD1 expression was enhanced in groupⅡ,yet weakened in groupⅠat P21 compared to at P14(both P<0.05),and the change was insignificant in groupⅢ(P>0.05).Conclusion:CD28 and PD1 on CD4^+T cells are abnormally expressed in premature mice.However,Changlekang may promote maturation and activation of CD4^+T cells through regulating CD28 and PD1 expression,thus improving the immune function of premature rats.