寿胎丸调控组蛋白修饰对复发性流产小鼠子宫内膜蜕膜化的影响OACSTPCD
Effects of Shoutai Pills in Regulating Histone Modification on Endometrial Decidualization of Mice with Recurrent Spontaneous Abortion
目的 观察寿胎丸对复发性流产(RSA)小鼠子宫内膜蜕膜化的影响,基于组蛋白修饰探讨其治疗RSA的可能作用机制.方法 将40只雌性CBA/J小鼠分为正常组、模型组、寿胎丸低剂量组(7.5 g/kg)、寿胎丸高剂量组(15 g/kg)和地屈孕酮组(3 mg/kg),正常组与BALB/C雄性小鼠合笼饲养,其余各组与DBA/2雄性小鼠合笼饲养建立RSA小鼠模型,造模后各给药组灌胃相应药液,正常组和模型组灌胃等体积纯水,连续10 d.观察胚胎情况,计算胚胎丢失率,ELISA检测血清泌乳素(PRL)含量,HE染色观察蜕膜组织形态,RT-PCR检测蜕膜组织PRL mRNA表达,Western blot检测蜕膜组织PRL、H4乙酰化(H4ac)、H3K27乙酰化(H3K27ac)、H3K27三甲基化(H3K27me3)蛋白表达.结果 与正常组比较,模型组小鼠胚胎丢失率明显升高,血清PRL含量明显减少,蜕膜细胞排列紊乱,出现大面积出血坏死;蜕膜组织PRL mRNA和蛋白表达明显降低,H4ac、H3K27ac蛋白表达明显降低,H3K27me3蛋白表达明显升高,差异均有统计学意义(P<0.05).与模型组比较,寿胎丸低、高剂量组和地屈孕酮组小鼠胚胎丢失率明显降低,血清PRL含量明显增加,蜕膜细胞排列紧密,坏死减少,腺体完整;寿胎丸高剂量组和地屈孕酮组小鼠蜕膜组织PRL mRNA和蛋白表达明显升高,H4ac、H3K27ac蛋白表达明显升高,H3K27me3蛋白表达明显降低,差异均有统计学意义(P<0.05).结论 寿胎丸可促进RSA小鼠子宫内膜蜕膜化,其机制与调节子宫内膜基质细胞组蛋白修饰有关.
Objective To observe the effect of Shoutai Pills on endometrial decidualization of mice with recurrent spontaneous abortion(RSA);To explore its possible mechanism in the treatment of RSA based on histone modification.Methods Totally 40 female CBA/J mice were divided into normal group,model group,Shoutai Pills low-dosage group(7.5 g/kg),Shoutai Pills high-dosage group(15 g/kg)and dydrogesterone group(3 mg/kg).The normal group were co housed with BALB/C male mice,while the other groups were co housed with DBA/2 male mice to establish an RSA mouse model.After modeling,the administration groups were given corresponding medication solution by gavage,while the normal group and model group were given equal volume of pure water by gavage for 10 consecutive days.The embryo condition was observed and the embryo loss rate was calculated,ELISA was used to detect serum prolactin(PRL)content,HE staining was used to observe the morphological changes of decidual tissue,RT-PCR was used to detect PRL mRNA expression in decidual tissue,Western blot was used to detect the protein expressions of H4ac,H3K27ac,H3K27me3.Results Compared with the normal group,the model group mice showed a significant increase in embryo loss rate,a significant decrease in serum PRL content,disordered arrangement of decidual cells,and extensive bleeding and necrosis;the expression of PRL mRNA and protein in decidual tissue significantly decreased,the protein expressions of H4ac and H3K27ac significantly decreased,while the expression of H3K27me3 protein significantly increased,with statistical significance(P<0.05).Compared with the model group,the embryo loss rate of Shoutai Pills low-and high-dosage groups and the dexamethasone group significantly decreased,the serum PRL content significantly increased,tightly arranged decidual cells,reduced necrosis,and intact glands;the expression of PRL mRNA and protein in decidual tissue of mice in Shoutai Pills high-dosage group and the dexamethasone group significantly increased,the protein expressions of H4ac and H3K27ac significantly increased,the expression of H3K27me3 protein significantly decreased,with statistical significance(P<0.05).Conclusion Shoutai Pills can promote endometrial decidualization in RSA mice,which is related to the changes of histone modification in endometrial stromal cells.
靳梓琪;任守杨;王天一;马珺卓;王子璐;张铭娜;张宇
河北中医药大学中西医结合学院(研究所),河北省中西医结合肝肾病证研究重点实验室,河北 石家庄 050200河北中医药大学基础医学院,河北 石家庄 050200石家庄市人民医院,河北 石家庄 050000
中医学
寿胎丸复发性流产蜕膜组织组蛋白修饰小鼠
Shoutai Pillsrecurrent spontaneous abortionendometrial decidualizationhistone modificationmice
《中国中医药信息杂志》 2024 (001)
104-109 / 6
国家自然科学基金联合基金(U21A20403);国家自然科学基金面上项目(82074247);河北省自然科学基金(H2021423031);河北省中医药管理局科研计划(2022182);河北省研究生创新项目(CXZZSS2022103);河北省大学生科技创新能力培育专项(22E50130D、22E50135D);国家大学生创新创业训练计划(202114432012)
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