圣世散对先兆流产模型小鼠细胞因子信号转导抑制因子蛋白表达的影响
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摘要
目的探讨圣世散对先兆流产模型小鼠母胎界面细胞因子信号转导抑制因子(SOCS)1、SOCS2、SOCS3蛋白表达的影响。方法采用雌性CBA/J小鼠与雄性BALB/c小鼠交配建立正常妊娠模型,雌性CBA/J小鼠与雄性DBA/2小鼠交配建立先兆流产模型,将先兆流产模型随机分为模型对照组,圣世散低、中、高剂量组,连续给药14d后处死取材,应用Western blot方法检测小鼠胎盘蜕膜组织SOCS1、SOCS2以及SOCS3蛋白的表达水平。结果 SOCS1、SOCS2、SOCS3在各组小鼠胎盘蜕膜组织中均有表达,SOCS1、SOCS3蛋白在小鼠胎盘蜕膜组织中的表达各组间差异有统计学意义(P均<0.05),SOCS2蛋白表达在各组间差异无统计学意义(P>0.05)。与正常妊娠组相比,先兆流产模型对照组SOCS1蛋白表达升高(P<0.05),先兆流产模型对照组及圣世散低剂量组SOCS3蛋白表达降低(P<0.05)。与先兆流产模型对照组相比,圣世散低剂量组小鼠SOCS1、圣世散低和中剂量组小鼠SOCS3蛋白表达差异均无统计学意义(P均>0.05),圣世散中、高剂量组可降低SOCS1蛋白表达,圣世散高剂量组可升高SOCS3蛋白表达(P<0.05),圣世散高剂量组与正常妊娠组比较差异无统计学意义(P>0.05)。结论圣世散高剂量组可通过影响SOCS的蛋白表达,调节妊娠母体免疫耐受,从而维持正常妊娠。
Objective To investigate the effects of Huihuifang Shengshisan on the expression of SOCS1,SOCS2 and SOCS3 in maternal-fetal interface of threatened abortion model mice. Methods The normal pregnancy model was established by mating female CBA/J mice with male BALB/c mice. The threatened abortion model was established by mating female CBA/J mice with male DBA/2 mice. The threatened abortion model was randomly divided into model control group,Shengshi powder low,medium and high dosage groups. The samples were sacrificed after 14 days of continuous administration. The expression levels of SOCS1,SOCS2 and SOCS3 in the placental decidua were detected by Western blot. Results SOCS1,SOCS2 and SOCS3 were all expressed in mouse placental decidua. The expression of SOCS1 and SOCS3 protein in decidua and placenta of mice was significantly different(P<0.05). There was no significant difference between all the groups on expression of SOCS2 protein(P>0.05). Compared with the normal pregnancy group,the expression of SOCS1 protein in the threatened abortion model control group was increased,and the expression of SOCS3 protein in the threatened abortion model control group and the low dose group of Shengshisan decreased,the difference was statistically significant(P<0. 05). Compared with the control group of the threatened abortion model,the low dose of Shengshisan had no significant effect on the expression of SOCS1 protein in threatened abortion mice. The low dose and middle dose group of Shengshisan had no significant effect on the expression of SOCS3 protein in threatened abortion mice(P>0.05). The middle and high dose group of Shengshisan significantly reduced the expression of SOCS1 protein in the maternal-fetal interface of the mice. The high dose of Shengshisan significantly increased the expression of SOCS3 protein,the difference was statistically significant(P<0.05).There was no significant difference between the dose group and the normal pregnancy group(P>0.05).Conclusion The high-dose group of Huihuifang Shengshisan can maintain the normal pregnancy by affecting the expression of SOCS protein,regulating the dynamic balance of the immune network and pregnancy immune tolerance.
Objective To investigate the effects of Huihuifang Shengshisan on the expression of SOCS1,SOCS2 and SOCS3 in maternal-fetal interface of threatened abortion model mice. Methods The normal pregnancy model was established by mating female CBA/J mice with male BALB/c mice. The threatened abortion model was established by mating female CBA/J mice with male DBA/2 mice. The threatened abortion model was randomly divided into model control group,Shengshi powder low,medium and high dosage groups. The samples were sacrificed after 14 days of continuous administration. The expression levels of SOCS1,SOCS2 and SOCS3 in the placental decidua were detected by Western blot. Results SOCS1,SOCS2 and SOCS3 were all expressed in mouse placental decidua. The expression of SOCS1 and SOCS3 protein in decidua and placenta of mice was significantly different(P<0.05). There was no significant difference between all the groups on expression of SOCS2 protein(P>0.05). Compared with the normal pregnancy group,the expression of SOCS1 protein in the threatened abortion model control group was increased,and the expression of SOCS3 protein in the threatened abortion model control group and the low dose group of Shengshisan decreased,the difference was statistically significant(P<0. 05). Compared with the control group of the threatened abortion model,the low dose of Shengshisan had no significant effect on the expression of SOCS1 protein in threatened abortion mice. The low dose and middle dose group of Shengshisan had no significant effect on the expression of SOCS3 protein in threatened abortion mice(P>0.05). The middle and high dose group of Shengshisan significantly reduced the expression of SOCS1 protein in the maternal-fetal interface of the mice. The high dose of Shengshisan significantly increased the expression of SOCS3 protein,the difference was statistically significant(P<0.05).There was no significant difference between the dose group and the normal pregnancy group(P>0.05).Conclusion The high-dose group of Huihuifang Shengshisan can maintain the normal pregnancy by affecting the expression of SOCS protein,regulating the dynamic balance of the immune network and pregnancy immune tolerance.
引文
[1]谢幸,苟文丽.妇产科学[M]. 8版.北京:人民卫生出版社,2014:48.
[2]符水秀.中医药治疗先兆流产新进展[J].中国民族民间医药杂志,2013,1:76-77.
[3]杜小利,刘敬霞,杨利霞,等.回回药方圣世散对早期先兆流产患者血人绒毛膜促性腺激素及孕激素的影响[J].宁夏医科大学学报,2014,3:245-247.
[4]何冬梅,尤昭玲,雷磊,等.寿胎丸对反复自然流产小鼠母胎界面SOCS1和SOCS3蛋白表达的影响[J].湖南中医药大学学报,2009,29(1):26-28.
[5] Clark DA,McDermott M,Sczewzuk MR. Impairment of host versus graft reaction in pregnant mice. II.Selective suppression of cytotoxic cell generation correlates with soluble suppressor activity and successful allogeneic pregnancy[J]. Cell Immunol,1980,52(1):106-118.
[6] Tangri S,Wegmann TG,Lin H,et al. Maternal antiplacental reactivity in natural,immunologically mediated fetal resorptions[J]. J Immuno1,1994,152(10):4903-4911.
[7] Achmann J,Raue A,Schilling M,et al. Division of labor by dual feedback regulators controls JAK2/STAT5 signaling over broad ligand range[J]. Mol Syst Biol,2011,19(7):516-520.
[8] Lindemann C,Hackmann O,Delic S,et al. SOCS3promoter methylation is mutually exclusive to EGFR amplification in gliomas and promotes glioma cell invasion through STAT3 and FAK activation[J]. Acta Neuropathol,2011,122(2):241-251.
[9] San Martin S,Fitzgerald JS,Weber M,et al. Stat3 and Socs3 expression patterns during murine placenta development[J]. Eur J Histochem,2013,57(2):19-23.
[10] Ilian MT,Joanne E. SOCS2 can enhance interleukin-2(IL-2)and IL-3 signaling by accelerating SOCS3 degradation[J]. Mol Celhxlar Biol,2005,25:9115.
[11] Kubo M,Hanada T,Yoshinura A. Suppressors of cymkine signaling and inmunity[J]. Nat Inmunol,2003,4(12):1169.
[12]何冬梅,尤昭玲,雷磊,等.寿胎丸对反复自然流产小鼠母胎界面SOCS1和SOCS3蛋白表达的影响[J].湖南中医药大学学报,2009,29(1):26-28.
[13]高如宏,陈卫川.《回族医方集粹》[M].银川:宁夏人民出版社,2008:213-214.
[14]杜小利,吴心芳,罗文玉,等.回回药方圣世散对早期先兆流产患者血人绒毛膜促性腺激素雌激素及孕激素的影响[J].四川中医,2013,31(11):63-65.
[15]杜小利,朱宁娃.回回药方圣世散治疗先兆流产35例[J].中医杂志,2012,53(3):217-218.
[2]符水秀.中医药治疗先兆流产新进展[J].中国民族民间医药杂志,2013,1:76-77.
[3]杜小利,刘敬霞,杨利霞,等.回回药方圣世散对早期先兆流产患者血人绒毛膜促性腺激素及孕激素的影响[J].宁夏医科大学学报,2014,3:245-247.
[4]何冬梅,尤昭玲,雷磊,等.寿胎丸对反复自然流产小鼠母胎界面SOCS1和SOCS3蛋白表达的影响[J].湖南中医药大学学报,2009,29(1):26-28.
[5] Clark DA,McDermott M,Sczewzuk MR. Impairment of host versus graft reaction in pregnant mice. II.Selective suppression of cytotoxic cell generation correlates with soluble suppressor activity and successful allogeneic pregnancy[J]. Cell Immunol,1980,52(1):106-118.
[6] Tangri S,Wegmann TG,Lin H,et al. Maternal antiplacental reactivity in natural,immunologically mediated fetal resorptions[J]. J Immuno1,1994,152(10):4903-4911.
[7] Achmann J,Raue A,Schilling M,et al. Division of labor by dual feedback regulators controls JAK2/STAT5 signaling over broad ligand range[J]. Mol Syst Biol,2011,19(7):516-520.
[8] Lindemann C,Hackmann O,Delic S,et al. SOCS3promoter methylation is mutually exclusive to EGFR amplification in gliomas and promotes glioma cell invasion through STAT3 and FAK activation[J]. Acta Neuropathol,2011,122(2):241-251.
[9] San Martin S,Fitzgerald JS,Weber M,et al. Stat3 and Socs3 expression patterns during murine placenta development[J]. Eur J Histochem,2013,57(2):19-23.
[10] Ilian MT,Joanne E. SOCS2 can enhance interleukin-2(IL-2)and IL-3 signaling by accelerating SOCS3 degradation[J]. Mol Celhxlar Biol,2005,25:9115.
[11] Kubo M,Hanada T,Yoshinura A. Suppressors of cymkine signaling and inmunity[J]. Nat Inmunol,2003,4(12):1169.
[12]何冬梅,尤昭玲,雷磊,等.寿胎丸对反复自然流产小鼠母胎界面SOCS1和SOCS3蛋白表达的影响[J].湖南中医药大学学报,2009,29(1):26-28.
[13]高如宏,陈卫川.《回族医方集粹》[M].银川:宁夏人民出版社,2008:213-214.
[14]杜小利,吴心芳,罗文玉,等.回回药方圣世散对早期先兆流产患者血人绒毛膜促性腺激素雌激素及孕激素的影响[J].四川中医,2013,31(11):63-65.
[15]杜小利,朱宁娃.回回药方圣世散治疗先兆流产35例[J].中医杂志,2012,53(3):217-218.