基于P38MAPK/P53信号通路探讨寿胎丸对复发性流产小鼠的影响*

作者：冯 玮，王艳辉，史力卉，雷 磊

单位：湖南中医药大学中西医结合学院，湖南 长沙 410208

引用：引用：冯玮，王艳辉，史力卉，雷磊.基于P38MAPK/P53信号通路探讨寿胎丸对复发性流产小鼠的影响[J].中医药导报,2025,31(4):67-72.

DOI：10.13862/j.cn43-1446/r.2025.04.011

PDF： 下载PDF

摘要：目的：观察寿胎丸对复发性流产（RSA）小鼠的影响，通过p38丝裂原活化蛋白激酶（P38MAPK）/抑癌基因（P53）信号通路研究其作用机理。方法：根据Clark的经典建模流程，将40只雌性CBA/J小鼠与20只雄性DBA/2小鼠以2∶1的比例进行合笼交配，构建RSA小鼠模型，将40只妊娠小鼠随机分为地屈孕酮组、模型组、寿胎丸高剂量组、寿胎丸中剂量组、寿胎丸低剂量组，每组8只。将8只雌性CBA/J小鼠与4只雄性BALB/c小鼠以2∶1的比例合笼，构建正常妊娠小鼠模型，将8只正常妊娠小鼠模型设置为空白组。各组小鼠予相应药物干预，观察小鼠的妊娠状态，并计算小鼠胚胎丢失率；苏木素-伊红（HE）染色观察各组小鼠胎盘组织病理学改变；Western blotting检测胎盘组织P38MAPK、磷酸化P38MAPK（p-P38MAPK）、P53、B细胞淋巴瘤-2（Bcl-2）蛋白表达；ELISA检测血清中MDA含量；PCR检测胎盘组织P38MAPK mRNA、p-P38MAPK mRNA、P53 mRNA、Bcl-2 mRNA表达。结果：空白组小鼠子宫淡红色，胚胎发育均衡，大小一致，排列有序；模型组小鼠胎盘形态破坏，细胞排列不规则、细胞核固缩；与模型组比较，地屈孕酮组、寿胎丸高剂量组、寿胎丸中剂量组、寿胎丸低剂量组大鼠胎盘组织内病理状态改善，细胞排列有序，形态较规则。模型组小鼠胚胎丢失率及血清MDA含量高于空白组（P<0.01）；寿胎丸高剂量组、寿胎丸中剂量组及地屈孕酮组小鼠胚胎丢失率及血清MDA含量均低于模型组（P＜0.01或P＜0.05）。模型组小鼠胎盘组织中p-P38MAPK/P38MAPK及P53蛋白相对表达量高于空白组（P<0.01），Bcl-2蛋白相对表达量低于空白组（P<0.01）；寿胎丸高剂量组、寿胎丸中剂量组及地屈孕酮组小鼠胎盘组织p-P38MAPK/P38MAPK及P53蛋白相对表达量均低于模型组（P<0.01）；寿胎丸高剂量组、寿胎丸中剂量组、寿胎丸低剂量组及地屈孕酮组小鼠胎盘组织Bcl-2蛋白相对表达量均高于模型组（P<0.01）。模型组小鼠胎盘组织P38MAPK mRNA及P53 mRNA相对表达量高于空白组（P<0.01），Bcl-2 mRNA相对表达量低于空白组（P<0.01）；寿胎丸高剂量组、寿胎丸中剂量组、寿胎丸低剂量组及地屈孕酮组小鼠胎盘组织P38MAPK mRNA及P53 mRNA相对表达量均低于模型组（P<0.01或P<0.05），Bcl-2 mRNA相对表达量均高于模型组（P<0.01）。结论：寿胎丸可能通过P38MAPK/P53信号通路调控氧化应激，发挥防治小鼠复发性流产的作用。

关键词：复发性流产；寿胎丸；P38MAPK/P53通路；氧化应激；小鼠

Abstract：Objective: To observe the effects of Shou Tai Wan on recurrent abortion (RSA) mice, and to study its mechanism of action through the P38MAPK/P53 signaling pathway. Methods: According to Clark's classical modeling procedure, 40 female CBA/J mice and 20 male DBA/2 mice were mated in a combined cage based on a 2∶1 ratio to construct the RSA mouse model, and 40 pregnant mice were randomly divided into dydrogesterone group, model group, Shou Tai Wan high dose group, Shou Tai Wan medium dose group, and Shou Tai Wan low dose group, with 8 mice in each group. Totally 8 female CBA/J mice and 4 male BALB/c mice were caged together based on a 2∶1 ratio to construct a normal pregnancy mouse model, and the 8 normal pregnancy mice model was set as blank group. The mice in each group were given appropriate drug interventions. The pregnancy status of the mice was observed, and the embryo loss rate was calculated. Hematoxylin-eosin (HE) staining was used to observe the histopathological changes in the placenta of the mice in each group. Western blotting detected p38 mitogen-activated protein kinase (P38MAPK), phosphorylated p38MAPK (p-P38MAPK), oncogene (P53), and B-cell lymphoma-2 (Bcl-2) protein expression. ELISA was used to detect MDA content in serum. PCR was used to detect the expression of P38MAPK mRNA, p-P38MAPK mRNA, P53 mRNA, and Bcl-2 mRNA in placental tissues. Results: The uterus of mice in the blank group was light red, with balanced embryonic development, uniform size and orderly arrangement. The placenta of mice in the model group was irregularly arranged with disrupted morphology and solidified cell nuclei. Compared with the model group, the pathological state of the placenta tissue was improved in the dydrogesterone group as well as the Shou Tai Wan high, medium and low dose groups, and the cellular arrangement was orderly with a more regular morphology. The model group showed higher embryo loss rate and serum MDA content than blank group (P<0.01). The Shou Tai Wan high dose group, Shou Tai Wan medium dose group and dydrogesterone group showed lower embryo loss rate and serum MDA content than model group (P<0.01 or P<0.05). The model group showed higher p-38MAPK/P38MAPK and relative expression of P53 proteins than blank group (P<0.01), while lower relative expression of Bcl-2 proteins than blank group (P<0.01). The Shou Tai Wan high dose group, Shou Tai Wan medium dose group and dydrogesterone group showed lower p-38MAPK/P38MAPK and relative expression of P53 proteins than model group (P<0.01). The Shou Tai Wan high dose group, Shou Tai Wan medium dose group, Shou Tai Wan low dose group and dydrogesterone group showed higher relative expression of Bcl-2 proteins than model group (P<0.01). The model group showed higher relative expression of P38MAPK mRNA and P53 mRNA than blank group (P<0.01), while lower relative expression of Bcl-2 mRNA than blank group (P<0.01). The Shou Tai Wan high dose group, Shou Tai Wan medium dose group, Shou Tai Wan low dose group and dydrogesterone group showed lower relative expression of P38MAPK mRNA and P53 mRNA than model group (P<0.01 or P<0.05), while higher relative expression of Bcl-2 mRNA than model group (P<0.01). Conclusion: Shou Tai Wan may regulate oxidative stress through the P38MAPK/P53 signaling pathway, and play a role in preventing recurrent abortion in mice.

Key words：recurrent miscarriage; Shou Tai Wan; P38MAPK/P53 pathway; oxidative stress; mice

发布时间：2025-12-20

点击量：19