雌激素诱导DCN基因甲基化在盆腔器官脱垂发病机制中的作用

崔淑岭; 劳佩维; 沈柯炜; 张英芝

doi:10.16766/j.cnki.issn.1674-4152.003795

雌激素诱导DCN基因甲基化在盆腔器官脱垂发病机制中的作用

doi: 10.16766/j.cnki.issn.1674-4152.003795

宁波大学附属第一医院妇科，浙江宁波 315211

基金项目:

浙江省医药卫生科技计划项目 2023KY1106

详细信息

通讯作者:
张英芝，E-mail：zyzzzc2007@163.com

中图分类号: R711.2
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- 文章访问数: 10
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- 被引次数: 0
出版历程
- 收稿日期: 2024-02-25
- 网络出版日期: 2025-01-20

The role of estrogen-induced DCN gene methylation in the pathogenesis of pelvic organ prolapse

Department of Gynaecology, the First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315211, China

摘要

摘要: 目的检测盆腔器官脱垂(POP) 患者雌二醇(E2)、核心蛋白聚糖(DCN)基因甲基化水平，并研究其在POP发病机制中的作用。方法选取2023年1月—2024年1月于宁波大学附属第一医院妇科行盆底重建手术治疗的85例POP患者为研究对象，根据术前激素水平及绝经时间分为绝经后期组(PSM组，44例)和绝经过渡期组(TRM组，41例)，另选取同期30例盆腔良性疾病患者为对照组。采用50 nmol/L雌激素(H-EST组)、2 nmol/L雌激素(L-EST组)、50 nmol/L雌激素联合ER拮抗(ESR siRNA，H-EST+siER组)及siER(siER组)处理原代成纤维细胞，未行任何处理的原代成纤维细胞为对照(CON组)。检测并比较E2、DCN、Ⅰ型胶原酶(COL Ⅰ)、E2受体(ER)、DCN基因甲基化差异。结果 PSM组患者E2、DCN、COL Ⅰ及ER表达均显著低于TRM组和对照组(P < 0.05)，DCN甲基化率均显著高于TRM组和对照组(P < 0.05)。PSM组和TRM组POP患者E2与DCN、COLⅠ均呈正相关关系(r_s=0.713、0.654、0.679、0.639，均P < 0.05)，与DCN基因甲基化呈负相关关系(r_s=-0.821、-0.806，P < 0.05)。H-EST组、L-EST组细胞DCN、COL Ⅰ及ER表达均显著低于CON组、H-EST+siER组及siER组(P < 0.05)，DCN甲基化率均显著高于CON组、H-EST+siER组及siER组(P < 0.05)。结论 POP患者E2及DCN基因甲基化率显著升高，两者呈负相关关系，E2可能通过诱导DCN基因甲基化参与POP发病机制。
- 盆腔器官脱垂 /
- 雌激素 /
- 核心蛋白聚糖 /
- 甲基化 /
- 发病机制
Abstract: Objective To detect the methylation of estradiol (E2) and decorin (DCN) genes in patients with pelvic organ prolapse (POP) and to study their role in the pathogenesis of POP. Methods A total of 85 POP patients who underwent surgery between January 2023 and January 2024 were selected for the postmenopause group (PSM group, n=44) and menopausal transition period group (TRM group, n=41), additionally, 30 patients with pelvic benign diseases during the same period were selected as the control group. The Primary fibroblasts were treated with 50 nmol/L E2 (H-EST group), 2 nmol/L E2 (L-EST group), and 50 nmol/L E2 in combination with an ER antagonist (ESR siRNA, H-EST+siER group). Detect and compare the methylation differences of the estradiol (E2), DCN, type Ⅰ collagenase (COL Ⅰ), E2 receptor (ER) and DCN genes. Results The expressions of E2, DCN, COL Ⅰ and ER in the PSM group were significantly lower than those in the TRM group and the control group (P < 0.05), Furthermore the DCN methylation rate was significantly higher in the PSM group than in the TRM group and the control group (P < 0.05). In patients with POP in the PSM group and TRM group, E2 was found to be positively correlated with the expression of DCN, COL Ⅰ, and ER (r_s=0.713, 0.654, 0.679, 0.639, respectively, all P < 0.05), and negatively correlated with DCN gene methylation (r_s=-0.821, -0.806, all P < 0.05). The expressions of DCN, COL Ⅰ and ER in cells of the H-EST group and L-EST group were significantly lower than those of the CON group, H-EST+siER group and siER group (P < 0.05). Furthermore, the DCN methylation rate was significantly higher than that of the CON group, H-EST+siER group and siER group (P < 0.05). Conclusion The methylation rate of DCN genes and E2 level is markedly elevated in patients with POP, and there is a negative correlation. E2 may play a role in the development of POP by inducing methylation of the DCN gene.
- Pelvic organ prolapse /
- Estrogen /
- Decorin /
- Methylation /
- Pathogenesis

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图 1 3组研究对象DCN、COL Ⅰ、ER表达情况

Figure 1. Expression of DCN, COL Ⅰ, and ER among the three groups of research subjects

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表 1 3组研究对象临床基线资料比较

Table 1. Comparison of clinical baseline data among

组别	例数	年龄 (x±s, 岁)	BMI (x±s)	产次 (x±s, 次)	重体力劳动 (是/否, 例)	分娩方式 (阴道/剖宫产, 例)
PSM组	44	54.7±6.2	23.5±3.9	1.5±0.5	8/36	31/13
TRM组	41	54.1±6.5	23.1±4.1	1.4±0.5	6/35	28/13
对照组	30	54.3±6.8	23.3±4.2	1.6±0.6	5/25	24/6
统计量		0.095^a	0.103^a	1.256^a	0.194^b	1.287^b
P值		0.910	0.902	0.289	0.907	0.525
注：^a为F值，^b为χ²值。

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表 2 3组研究对象E2、DCN、COL Ⅰ、ER表达及DCN基因甲基化率比较(x±s)

Table 2. Comparison of E2, DCN, COL Ⅰ, ER expression, and DCN gene methylation rate among the three groups of research subjects

组别	例数	E2 (nmol/L)	DCN	COL Ⅰ	ER	DCN甲基化率(%)
PSM组	44	50.2±13.2^ab	0.4±0.1^ab	0.5±0.1^ab	0.3±0.1^ab	61.5±7.2^ab
TRM组	41	147.8±25.6^b	0.6±0.2^b	0.7±0.1^b	0.5±0.2^b	52.3±6.5^b
对照组	30	183.5±31.1	0.8±0.2	0.8±0.2	0.7±0.2	36.8±4.9
F值		332.811	50.766	49.738	50.766	132.254
P值		< 0.001	< 0.001	< 0.001	< 0.001	< 0.001
注：与TRM组比较，^aP < 0.05；与对照组比较，^bP < 0.05。

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表 3 2组POP患者E2与DCN、COL Ⅰ、ER表达及DCN基因甲基化率的相关性

Table 3. The Correlation between E2 and DCN, COL Ⅰ, ER expression, and DCN gene methylation rate in the two groups of POP patients

组别	DCN		COL Ⅰ		DCN甲基化率
组别	r_s值	P值	r_s值	P值	r_s值	P值
PSM组	0.713	0.021	0.654	0.017	-0.821	0.037
TRM组	0.679	0.015	0.639	0.021	-0.806	0.021

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表 4 各组原代成纤维细胞DCN、COL Ⅰ、ER表达及DCN基因甲基化率比较(x±s)

Table 4. Comparison of DCN, COL Ⅰ, ER expression, and DCN gene methylation rate in the four groups of primary fibroblasts

组别	n	DCN	COL Ⅰ	ER	DCN甲基化率(%)
H-EST组	9	0.2±0.1	0.3±0.1	0.4±0.1	47.8±4.5
L-EST组	9	0.4±0.1	0.5±0.1	0.6±0.1	41.3±4.2
CON组	9	0.6±0.2^ab	0.8±0.1^ab	0.8±0.2^ab	32.1±3.7^ab
H-EST+siER组	9	0.6±0.1^ab	0.8±0.2^ab	0.9±0.3^ab	31.9±3.5^ab
siER组	9	0.6±0.1^ab	0.8±0.2^ab	0.9±0.2^ab	32.2±3.8^ab
F值		18.857	18.001	14.750	33.586
P值		< 0.001	< 0.001	< 0.001	< 0.001
注：与H-EST组比较，^aP < 0.05；与L-EST组比较，^bP < 0.05。

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