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定坤丹介导的TGF-β1/Smad2信号通路对颗粒细胞增殖和凋亡的影响

Dingkun Pill-Mediated TGF-β1/Smad2 Pathway Effects on Granulosa Cell Proliferation and Apoptosis.

作者信息

Chen Lan, Yan Xiaojing, Lian Yuanpei, Wang Dijun, Cai Jiali, Yin Chunyan, Cao Ji

机构信息

Meng Research Institute, Changzhou Traditional Chinese Medicine Hospital, Changzhou, 213003, Jiangsu, China.

出版信息

Mol Biotechnol. 2025 Apr 25. doi: 10.1007/s12033-025-01439-z.

DOI:10.1007/s12033-025-01439-z
PMID:40278965
Abstract

To investigate influences of Dingkun Pill on granulosa cell proliferation and apoptosis (P&A) in polycystic ovary syndrome (PCOS) mice and its association with the TGF-β1/Smad2 signaling pathway (SPW) activity. Forty-eight female SD mice were rolled into experimental group (EG, Dingkun Pill), control group (CG, metformin), model group (MG, distilled water), and normal group (NG, distilled water), with 12 mice per group. The Beloosesky method was employed to establish the PCOS mouse model. Serum hormone (follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T)), expression of vascular endothelial growth factor (VEGF) in rat ovarian tissue and expression of HOXA10 in endometrial tissue, cell P&A, and expression level (EL) of TGF-β1 and Smad2 were compared among groups. Compared to the MG, the EG and CG exhibited significantly reduced levels of FSH, LH, and testosterone, while estradiol levels were significantly elevated. Furthermore, granulosa cell proliferation was notably enhanced, and the apoptosis rate was significantly decreased (P < 0.05). In addition, the expression of VEGF in ovarian tissue, as well as the expression of TGF-β1 and Smad2, was significantly lower in EG and CG compared to MG, while the expression of the HOXA10 gene in the endometrium was significantly increased (P < 0.05). Compared to CG, EG showed higher ovarian VEGF expression and lower HOXA10 gene expression (P < 0.05).Dingkun Pill notably improves serum hormone in a PCOS mouse model, inhibits granulosa cell apoptosis, and enhances granulosa cell proliferation activity. This effect is likely mediated through the inhibition of the TGF-β1/Smad2 SPW, suggesting a protective role of Dingkun Pill in PCOS.

摘要

探讨定坤丹对多囊卵巢综合征(PCOS)小鼠颗粒细胞增殖和凋亡(P&A)的影响及其与转化生长因子-β1/信号转导分子Smad2信号通路(SPW)活性的关系。将48只雌性SD小鼠分为实验组(EG,定坤丹)、对照组(CG,二甲双胍)、模型组(MG,蒸馏水)和正常组(NG,蒸馏水),每组12只。采用Beloosesky法建立PCOS小鼠模型。比较各组血清激素(促卵泡生成素(FSH)、促黄体生成素(LH)、睾酮(T))、大鼠卵巢组织中血管内皮生长因子(VEGF)的表达、子宫内膜组织中HOXA10的表达、细胞P&A以及转化生长因子-β1和Smad2的表达水平(EL)。与MG组相比,EG组和CG组的FSH、LH和睾酮水平显著降低,而雌二醇水平显著升高。此外,颗粒细胞增殖明显增强,凋亡率显著降低(P<0.05)。另外,与MG组相比,EG组和CG组卵巢组织中VEGF的表达以及转化生长因子-β1和Smad2的表达显著降低,而子宫内膜中HOXA10基因的表达显著增加(P<0.05)。与CG组相比,EG组卵巢VEGF表达较高,HOXA10基因表达较低(P<0.05)。定坤丹显著改善PCOS小鼠模型的血清激素水平,抑制颗粒细胞凋亡,并增强颗粒细胞增殖活性。这种作用可能是通过抑制转化生长因子-β1/信号转导分子Smad2信号通路介导的,提示定坤丹对PCOS具有保护作用。

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