The Effect and Mechanism of Metformin on Inflammation in Polycystic Ovary Syndrome Model Rats

doi:10.12280/gjfckx.20250895

Abstract

Abstract:

Objective: To investigate the effect of metformin on the inflammatory response in polycystic ovary syndrome (PCOS) model rats and its regulatory role in the mitogen-activated protein kinase (MAPK)/nuclear factor-κB (NF-κB) pathway. Methods: Among 50 female SD rats, 40 rats were used to establish a PCOS model via letrozole induction and then randomly divided into the model group and low-, medium-, and high-dose metformin groups (n=10 each). The remaining 10 rats served as the control group. The low-, medium- and high-dose metformin groups were administered metformin via oral gavage at doses of 50 mg/kg, 100 mg/kg, and 200 mg/kg, respectively (all at a volume of 5 mL/kg). The control and model groups received 5 mL/kg normal saline via oral gavage. All treatments were administered once daily for four consecutive weeks. The estrous cycle changes were observed. Serum sex hormone levels [follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E₂), testosterone (T)] and inflammatory factor levels [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-18] were measured by enzyme-linked immunosorbent assay (ELISA). Ovarian morphology was examined via hematoxylin and eosin (HE) staining, and ovarian cell apoptosis was assessed via TUNEL staining. The expression levels of extracellular signal-regulated kinase (ERK), phosphorylated ERK (p-ERK), c-Jun N-terminal protein kinase (JNK), p-JNK, p38 MAPK, p-p38 MAPK, NF-κB p65, and p-NF-κB p65 proteins in ovarian tissues were detected by Western blotting. Results: The estrous cycle was disordered in the model group, while all metformin-treated groups showed improvements, with the most significant improvement observed in the high-dose metformin group. Compared with the control group, the model group exhibited decreased serum levels of FSH and E₂, and increased levels of LH, T, inflammatory factors, apoptosis rate, and the expression of p-ERK, p-JNK, p-p38 MAPK and p-NF-κB p65 proteins (all P<0.05). Compared with the model group, all metformin-treated groups demonstrated increased levels of FSH and E₂, and decreased levels of LH, T, inflammatory factors, apoptosis rate, and the expression of p-ERK, p-JNK, p-p38 MAPK and p-NF-κB p65 proteins, with the most significant improvements observed in the high-dose metformin group (all P<0.05). Ovarian morphology abnormalities improved in all metformin-treated groups, most notably in the high-dose metformin group. Conclusions: Metformin can improve the estrous cycle, regulate sex hormones, and reduce cell apoptosis in PCOS rats. Its mechanism of action may involve alleviating the inflammatory response by inhibiting the MAPK/NF-κB pathway.

Key words: Polycystic ovary syndrome, Rats, Inflammation, Mitogen-activated protein kinases, Nuclear factor-κB

ZHAO Xing-min, LIU Yan-ping, GAO Zheng, ZHANG Guo-qing. The Effect and Mechanism of Metformin on Inflammation in Polycystic Ovary Syndrome Model Rats[J]. Journal of International Obstetrics and Gynecology, 2026, 53(2): 143-149.

Figures/Tables 7

References 21

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组别	n	FSH（ng/mL）	LH（mg/mL）	E₂（pg/mL）	T（ng/mL）
对照组	10	6.34±0.54	8.42±0.92	182.59±15.58	1.96±0.23
模型组	10	2.96±0.39^a	21.46±1.58^a	124.79±10.73^a	3.49±0.31^a
二甲双胍低剂量组	10	3.75±0.42^ab	17.48±1.33^ab	139.68±11.85^ab	3.01±0.29^ab
二甲双胍中剂量组	10	4.46±0.48^abc	14.26±1.29^abc	152.36±12.96^abc	2.71±0.26^abc
二甲双胍高剂量组	10	5.57±0.53^abcd	11.38±1.11^abcd	166.96±13.38^abcd	2.27±0.25^abcd
F		81.570	162.299	30.220	50.387
P		<0.001	<0.001	<0.001	<0.001

组别	n	FSH（ng/mL）	LH（mg/mL）	E₂（pg/mL）	T（ng/mL）
对照组	10	6.34±0.54	8.42±0.92	182.59±15.58	1.96±0.23
模型组	10	2.96±0.39^a	21.46±1.58^a	124.79±10.73^a	3.49±0.31^a
二甲双胍低剂量组	10	3.75±0.42^ab	17.48±1.33^ab	139.68±11.85^ab	3.01±0.29^ab
二甲双胍中剂量组	10	4.46±0.48^abc	14.26±1.29^abc	152.36±12.96^abc	2.71±0.26^abc
二甲双胍高剂量组	10	5.57±0.53^abcd	11.38±1.11^abcd	166.96±13.38^abcd	2.27±0.25^abcd
F		81.570	162.299	30.220	50.387
P		<0.001	<0.001	<0.001	<0.001

组别	n	TNF-α	IL-6	IL-18
对照组	10	42.89±4.24	53.52±5.42	19.89±1.24
模型组	10	83.76±7.61^a	117.15±9.69^a	43.75±3.57^a
二甲双胍低剂量组	10	72.23±6.31^ab	96.43±9.11^ab	36.23±3.31^ab
二甲双胍中剂量组	10	61.68±5.11^abc	83.14±8.58^abc	29.68±2.07^abc
二甲双胍高剂量组	10	52.21±4.85^abcd	67.46±6.47^abcd	23.21±1.85^abcd
F		78.512	95.394	142.592
P		<0.001	<0.001	<0.001

组别	n	TNF-α	IL-6	IL-18
对照组	10	42.89±4.24	53.52±5.42	19.89±1.24
模型组	10	83.76±7.61^a	117.15±9.69^a	43.75±3.57^a
二甲双胍低剂量组	10	72.23±6.31^ab	96.43±9.11^ab	36.23±3.31^ab
二甲双胍中剂量组	10	61.68±5.11^abc	83.14±8.58^abc	29.68±2.07^abc
二甲双胍高剂量组	10	52.21±4.85^abcd	67.46±6.47^abcd	23.21±1.85^abcd
F		78.512	95.394	142.592
P		<0.001	<0.001	<0.001

组别	n	p-ERK	p-JNK	p-p38 MAPK	p-NF-κB p65
对照组	10	0.21±0.03	0.19±0.02	0.26±0.04	0.28±0.03
模型组	10	1.07±0.09^a	0.94±0.08^a	0.84±0.07^a	0.91±0.09^a
二甲双胍低剂量组	10	0.82±0.06^ab	0.76±0.07^ab	0.71±0.06^ab	0.77±0.07^ab
二甲双胍中剂量组	10	0.69±0.05^abc	0.57±0.05^abc	0.57±0.05^abc	0.58±0.06^abc
二甲双胍高剂量组	10	0.43±0.04^abcd	0.38±0.04^abcd	0.42±0.04^abcd	0.46±0.05^abcd
F		324.005	253.897	168.355	149.563
P		<0.001	<0.001	<0.001	<0.001