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谌泽芳,李泽潞,李涵宇,李艳军,余曦明,张伟,贺冰.少腹逐瘀汤改善高胰岛素血症小鼠子宫内膜容受性的机制研究[J].湖南中医药大学学报英文版,2022,42(10):1632-1640.[Click to copy
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| 少腹逐瘀汤改善高胰岛素血症小鼠子宫内膜容受性的机制研究 |
| 谌泽芳,李泽潞,李涵宇,李艳军,余曦明,张伟,贺冰 |
| (湖南中医药大学, 湖南 长沙 410208;湖南中医药大学第二附属医院, 湖南 长沙 410005) |
| 摘要: |
| 目的 探讨少腹逐瘀汤对高胰岛素血症小鼠子宫内膜容受性的影响及作用机制。方法 从70只SPF级雌性小鼠中随机选取10只作为正常组，其余小鼠构建高胰岛素血症所致子宫内膜容受性受损的动物模型。造模成功后雌、雄鼠2∶1进行合笼。孕鼠随机分为正常组、模型组、阿司匹林组（7.500 mg/kg）、戊酸雌二醇组（0.104 mg/kg）、少腹逐瘀汤正常剂量组、少腹逐瘀汤高剂量组（7.500、15.000 g/kg），10只/组。交配日后第5天观察小鼠胞饮突表达，交配日后第10天记录各组着床位点数。比较各组小鼠血糖、血清胰岛素水平和子宫环氧合酶２（cyclooxygenase-2， COX-2）、白血病抑制因子（leuke-mia inhibitory, LIF）、溶血磷脂酸受体３（lysophosphatidic acid receptor 3, LPAR3）蛋白及整合素αvβ3 mRNA表达。结果 交配日后第5天，与正常组比较，模型组子宫发育不良，胞饮突发育差，血糖、血清胰岛素水平均明显升高（P<0.01），子宫内膜COX-2、LIF、LPAR3蛋白和整合素αvβ3 mRNA表达均明显降低（P<0.01）；与模型组比较，各药物组子宫发育好，胞饮突发育良好，血糖和血清胰岛素水平均明显降低（P<0.05），子宫内膜COX-2、LIF、LPAR3蛋白表达均明显升高（P<0.05），阿司匹林组、少腹逐瘀汤高剂量组整合素αvβ3 mRNA表达均明显升高（P<0.01）。交配日后第10天，与正常组比，模型组平均胚胎着床位点数明显减少（P<0.05），血糖、血清胰岛素水平均明显升高（P<0.01），子宫内膜COX-2、LIF、LPAR3蛋白和整合素αvβ3 mRNA表达均明显降低（P<0.01）；与模型组比较，各药物组平均胚胎着床位点数均明显增多（P<0.05），血清胰岛素水平均明显降低（P<0.05，P<0.01），子宫内膜COX-2、LIF、LPAR3蛋白表达均明显升高（P<0.05，P<0.01）。结论 少腹逐瘀汤能增加子宫内膜容受性受损小鼠胚胎着床位点数，改善子宫内膜容受性，其机制可能与调节糖代谢水平，影响子宫内膜整合素αvβ3 mRNA的表达，上调COX-2、LIF、LPAR3蛋白的表达有关。 |
| 关键词: 少腹逐瘀汤 子宫内膜容受性 高胰岛素血症 整合素 环氧合酶2 白血病抑制因子 溶血磷脂酸受体3 |
| DOI：10.3969/j.issn.1674-070X.2022.10.008 |
| Received:April 27, 2022 |
| 基金项目:第六批全国老中医药专家学术经验继承工作继承人项目（国中医药人教发〔2017〕29号）；湖南省自然科学基金项目（2019JJ50459）。 |
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| Mechanism of Shaofu Zhuyu Decoction on improving endometrial receptivity in mice with hyperinsulinemia |
| CHEN Zefang,LI Zelu,LI Hanyu,LI Yanjun,YU Ximing,ZHANG Wei,HE Bing |
| (Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;The Second Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410005, China) |
| Abstract: |
| Objective To explore the effect and mechanism of Shaofu Zhuyu Decoction on endometrial receptivity in mice with hyperinsulinemia. Methods A total of 70 SPF female mice were randomly divided into normal group (n=10) and the rest to establish the animal model of endometrial receptivity damage caused by hyperinsulinemia. After successful modeling, the female and male mice were closed in one cage with the proportion of 2:1. Pregnant mice were randomly divided into normal group, model group, aspirin group (7.500 mg/kg), Progynova group (0.104 g/kg), Shaofu Zhuyu Decoction normal (7.500 g/kg, equivalent to clinical dose) and high-dose groups (15.000 g/kg, 2 times of clinical dose), 10 mice in each group. The expression of pinopode in mice was observed on the 5th day after mating, and the number of implantation points in each group was recorded on the 10th day after mating. The mRNA expression levels of blood glucose, serum insulin, cyclooxygenase-2 (COX-2), leukemia inhibitory factor (LIF), lysophosphatidic acid receptor 3 (LPAR3) protein and integrin alphavbeta 3 (αvβ3) in uterus of mice in each group were compared. Results On the fifth day after mating, compared with normal group, model group showed poor development of uterus and pinopode, significant higher blood glucose and serum insulin (P<0.01), and significant lower mRNA expression levels of COX-2, LIF, LPAR3 and αvβ3 in endometrium (P<0.01). Compared with model group, all drug groups showed normal development of uterus and pinopode, significant lower blood glucose and serum insulin (P<0.05), higher expression levels of COX-2, LIF, and LPAR3 in endometrium (P<0.05). Compared with model group, there was significant higher mRNA expression of αvβ3 for aspirin group and high-dose group of Shaofu Zhuyu Decoction (P<0.01). On the 10th day after mating, there was significant lower number of embryo implantation sites (P<0.05), higher level of blood glucose and serum insulin (P<0.01), and lower mRNA expression levels of COX-2, LIF, LPAR3 and αvβ3 (P<0.01) in model group than normal group; there was significant higher number of embryo implantation site (P<0.05), lower level of serum insulin (P<0.05, P<0.01), higher expression levels of COX-2, LIF, LPAR3 (P<0.05, P<0.01) in drug groups than model group. Conclusion Shaofu Zhuyu Decoction may increase the number of embryo implantation sites for mice with endometrial receptivity damage and improve endometrial receptivity. The mechanism may be related with regulating sugar metabolism level, influencing mRNA expression of αvβ3 and up-regulation of COX-2, LIF and LPAR3. |
| Key words: Shaofu Zhuyu Decoction endometrial receptivity hyperinsulinemia integrin cyclooxygenase-2 leukemia inhibitory lysophosphatidic acid receptor 3 |
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