The effect of icariin on apoptosis of ovarian granulosa cells in polycystic ovary syndrome rats by regulating the SDF-1/CXCR4 signaling pathway

doi:10.11958/20231504

Abstract

Abstract:

Objective To investigate the effect of icariin on apoptosis of ovarian granulosa cells in rats with polycystic ovarian syndrome (PCOS) by regulating stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor-4 (CXCR4) signal axis. Methods Granular cells successfully isolated from ovarian tissue of rats in the PCOS model group were grouped into the PCOS group, the low-dose icariin group, the medium-dose icariin group, the high-dose icariin group, the Rr-SDF-1 group and the high-dose icariin+Rr-SDF-1 group. Granular cells successfully isolated from ovarian tissue of rats in the normal control group were taken as the control group. Enzyme-linked immunosorbent assay (ELISA) was applied to detect levels of follicle-stimulating hormone (FSH), testosterone (T) and luteinizing hormone (LH) in supernatant of ovarian granulosa cells. CCK-8 method and EdU staining were applied to detect granulosa cell proliferation. Flow cytometry was applied to detect granulosa cell apoptosis. Western blot assay was applied to detect the expression of Bcl-2 associated X (Bax), Cleaved aspartate-specific cysteine protease-3 (Cleaved Caspase-3), SDF-1, and CXCR4 proteins in granulosa cells. Results Compared with the control group, the FSH level, OD₄₅₀ value and EdU positive cell rate were decreased in the PCOS group, and T and LH levels, apoptosis rate, Bax, Cleaved Caspase-3, SDF-1 and CXCR4 protein expression increased (P<0.05). Compared with PCOS group, the FSH level, OD₄₅₀ value and EdU positive cell rate were increased sequentially in the icariin low, medium and high dose groups, T and LH levels, apoptosis rate, Bax, Cleaved Caspase-3, SDF-1 and CXCR4 protein expression levels were decreased sequentially, and change trends of corresponding indicators were opposite to the above in the Rr-SDF-1 group (P<0.05). Compared with the high-dose icariin group, FSH level, OD₄₅₀ value and EdU positive cell rate were decreased in the high-dose icariin+Rr-SDF-1 group, and T and LH levels, apoptosis rate, Bax, Cleaved Caspase-3, SDF-1 and CXCR4 protein expression levels were increased (P<0.05). Conclusion Icariin may inhibit the apoptosis of ovarian granulosa cells in PCOS rats by inhibiting the SDF-1/CXCR4 signaling pathway.

Key words: icariin, stromal cell-derived factor-1/CXC chemokine receptor-4 signaling pathway, polycystic ovarian syndrome, granular cells, proliferation, apoptosis

CLC Number:

R285.5

Figures/Tables 8

References 20

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组别	FSH/（U/L）	T/（nmol/L）	LH/（U/L）
对照组	72.25±3.11	1.01±0.08	58.65±2.33
PCOS组	26.69±1.25^a	2.46±0.12^a	84.47±3.13^a
淫羊藿苷低剂量组	31.17±1.36^b	2.04±0.11^b	78.56±3.08^b
淫羊藿苷中剂量组	40.55±1.87^bc	1.58±0.09^bc	72.86±3.01^bc
淫羊藿苷高剂量组	63.35±2.81^bcd	1.11±0.07^bcd	64.43±2.85^bcd
Rr-SDF-1组	19.96±0.87^b	2.87±0.14^b	89.96±2.77^b
淫羊藿苷高剂量+ Rr-SDF-1组	35.67±1.62^e	1.63±0.09^e	71.88±2.93^e
F	564.801^＊＊	267.652^＊＊	86.309^＊＊

组别	FSH/（U/L）	T/（nmol/L）	LH/（U/L）
对照组	72.25±3.11	1.01±0.08	58.65±2.33
PCOS组	26.69±1.25^a	2.46±0.12^a	84.47±3.13^a
淫羊藿苷低剂量组	31.17±1.36^b	2.04±0.11^b	78.56±3.08^b
淫羊藿苷中剂量组	40.55±1.87^bc	1.58±0.09^bc	72.86±3.01^bc
淫羊藿苷高剂量组	63.35±2.81^bcd	1.11±0.07^bcd	64.43±2.85^bcd
Rr-SDF-1组	19.96±0.87^b	2.87±0.14^b	89.96±2.77^b
淫羊藿苷高剂量+ Rr-SDF-1组	35.67±1.62^e	1.63±0.09^e	71.88±2.93^e
F	564.801^＊＊	267.652^＊＊	86.309^＊＊

组别	OD₄₅₀值	EdU阳性细胞率/%	凋亡率/%
对照组	1.08±0.10	57.94±2.68	8.78±0.31
PCOS组	0.37±0.03^a	12.96±0.51^a	27.75±1.27^a
淫羊藿苷低剂量组	0.49±0.04^b	20.33±0.86^b	22.15±1.33^b
淫羊藿苷中剂量组	0.62±0.05^bc	29.95±1.37^bc	18.06±0.71^bc
淫羊藿苷高剂量组	0.87±0.08^bcd	43.36±2.45^bcd	11.53±0.62^bcd
Rr-SDF-1组	0.22±0.01^b	7.35±0.21^b	32.34±1.58^b
淫羊藿苷高剂量+ Rr-SDF-1组	0.53±0.04^e	24.56±1.08^e	19.94±0.87^e
F	156.952^＊＊	753.575^＊＊	384.293^＊＊

组别	OD₄₅₀值	EdU阳性细胞率/%	凋亡率/%
对照组	1.08±0.10	57.94±2.68	8.78±0.31
PCOS组	0.37±0.03^a	12.96±0.51^a	27.75±1.27^a
淫羊藿苷低剂量组	0.49±0.04^b	20.33±0.86^b	22.15±1.33^b
淫羊藿苷中剂量组	0.62±0.05^bc	29.95±1.37^bc	18.06±0.71^bc
淫羊藿苷高剂量组	0.87±0.08^bcd	43.36±2.45^bcd	11.53±0.62^bcd
Rr-SDF-1组	0.22±0.01^b	7.35±0.21^b	32.34±1.58^b
淫羊藿苷高剂量+ Rr-SDF-1组	0.53±0.04^e	24.56±1.08^e	19.94±0.87^e
F	156.952^＊＊	753.575^＊＊	384.293^＊＊

组别	Bax	Cleaved Caspase-3	SDF-1	CXCR4
对照组	0.56±0.04	0.36±0.04	0.39±0.02	0.26±0.02
PCOS组	1.37±0.11^a	0.89±0.07^a	1.68±0.13^a	1.01±0.10^a
淫羊藿苷低剂量组	1.12±0.09^b	0.73±0.06^b	1.25±0.11^b	0.86±0.07^b
淫羊藿苷中剂量组	0.95±0.08^bc	0.61±0.05^bc	0.78±0.06^bc	0.49±0.05^bc
淫羊藿苷高剂量组	0.70±0.05^bcd	0.43±0.03^bcd	0.56±0.04^bcd	0.37±0.04^bcd
Rr-SDF-1组	1.69±0.12^b	1.05±0.08^b	2.21±0.13^b	1.33±0.09^b
淫羊藿苷高剂量+Rr-SDF-1组	0.97±0.08^e	0.66±0.05^e	1.03±0.11^e	0.68±0.07^e
F	121.771^＊＊	110.491^＊＊	273.868^＊＊	186.704^＊＊