Notch信号通路在多囊卵巢综合征诱导心肌纤维化过程中的作用及分子机制

任楠楠; 周珊; 段海霞

doi:10.12125/j.chj.202107075

Notch信号通路在多囊卵巢综合征诱导心肌纤维化过程中的作用及分子机制

Role and molecular mechanism of Notch signaling pathway in the process of myocardial fibrosis mediated by polycystic ovary syndrome

摘要

摘要:
目的探讨Notch信号通路对多囊卵巢综合征诱导心肌纤维化进程的作用及其机制研究。
方法将来曲唑通过灌胃的建模方式建立大鼠的PCOS模型；实验分为：阴性对照组、来曲唑干预组（200 μg/d）、Notch1激动剂Jagged1处理组、Notch1激动剂Jagged1+来曲唑干预组（200 μg/d），建模时间为21 d，分别收集各组大鼠的血清检测雌二醇（E2）、促卵泡生长激素（FSH）含量的改变。称取SD大鼠心脏的质量和体质量，计算各组心脏系数。运用RT-PCR检测I型心肌胶原和III型心肌胶原在各组实验SD大鼠心肌中的改变。利用血液生化分析仪对各组SD大鼠血清中TG、TC、HDL、LDL以及ApoAI/ApoB。运用Western blot检测各组心脏组织中Notch信号通路相关分子的改变。
结果运用来曲唑灌胃的方式能够成功建立PCOS模型，模型组血清中TG、LDL与对照组血清相比含量显著升高（P<0.01），ApoAI/ApoB显著降低（P<0.05）。心脏系数PCOS模型组与对照组相比显著升高（P<0.05）。PCOS组胶原蛋白增加（P<0.05），Notch信号通路相关分子处于抑制状态。Notch信号通路的激动剂干预对血清中E2和FSH含量并无影响，Notch信号通路的激动剂干预能够抑制来曲唑诱导的大鼠心肌细胞胶原蛋白的表达升高（P<0.05）。
结论 Notch信号通路能够抑制PCOS介导的心肌纤维化进程，对PCOS引起的心血管疾病的发生具有保护作用。

Abstract:
AIM To investigate the role and mechanism of Notch signaling pathway in myocardial fibrosis induced by polycystic ovary syndrome.
METHODS Rats were given letrozole by gavage to establish PCOS model. The experiment was divided into: negative control group, letrozoleintervention group 200 μg/d, Notch1 agonist Jagged1 treatment group, Notch1 agonist Jagged1+ letrozole intervention group (200 μg/d). The changes of serum levels of estradiol (E2) and follicle-stimulating growth hormone (FSH) in each group were observed after successful modeling on 21 d. HE staining was used to detect the morphological changes of ovary in each group. Changes of molecules related to Notch signaling pathway in heart tissues of each group were detected by Western blot.
RESULTS PCOS model was successfully established by gavage of letrozole. Compared with the control group, TG, TC, HDL and LDL in serum were significantly increased in the PCOS model group (P<0.05). Heart coefficient of PCOS model group was significantly higher than that of the control group (P<0.05). In the PCOS group, the myocardial cells showed fibrotic changes, collagen increased, and molecules related to Notch signaling pathway were inhibited. The agonist intervention of Notch signaling pathway had no effect on the serum content and inhibited letrozole-induced increased collagen expression in rat cardiomyocytes.
CONCLUSION Notch signaling pathway can inhibit the process of myocardial fibrosis mediated by PCOS and has a protective effect on the occurrence of cardiovascular diseases caused by PCOS.

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