Effects of acacetin on angiogenesis in diabetes retinopathy rats by regulating Hippo signaling pathway

doi:10.11958/20230889

Abstract

Abstract:

Objective To investigate the impact of acacetin (Aca) on angiogenesis in diabetes retinopathy (DR) rats by regulating Hippo signaling pathway. Methods Sixty SD rats were grouped into the control group, the DR group, the Aca low dose group (10 mg/kg), the Aca medium dose group (20 mg/kg), the Aca high dose group (30 mg/kg) and Hippo-YAP signaling pathway inhibitor Verteporfin group (Aca high dose 30 mg/kg+Verteporfin 0.8 pmol/kg), with 10 rats in each group. Except the control group, streptozotocin and high-fat feed were used to construct the DR model. Body weight and fasting blood glucose (FBG) levels of rats were measured. Fluorescein angiography (FFA) was applied to observe retinal angiogenesis and fluorescein leakage. Enzyme linked immunosorbent assay was applied to detect serum levels of vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2). Pathological changes of retinal tissue were observed by hematoxylin-eosin staining. Western blot assay was applied to detect expression levels of VEGF, hypoxia-inducible factor 1 alpha (HIF-1α), vascular cell adhesion molecule-1 (VCAM-1) and Hippo signaling pathway proteins. Results Compared with the control group, retinal cells of rats in the DR group were arranged in a disordered and loose manner, with neovascularization and a large amount of fluorescein leakage, and body weight, the expression of large tumor suppressor homolog 2 (LATS2), p-Yes-associated protein (YAP) were reduced. FBG and expression levels of VEGF, Ang-2, HIF-1α, VCAM-1, YAP, transcription activator with PDZ binding motif (TAZ), TEA domain family member 1 (TEAD1) were increased (P<0.05). Compared with the DR group, retina cells of rats in the Aca low, medium and high-dose groups and the Verteporfin group were arranged neatly, with reduced neovascularization and fluorescence leakage, body weight and the expression levels of LATS2 and p-YAP were increased, and FBG, expression levels of VEGF, Ang-2, HIF-1α, VCAM-1, YAP, TAZ and TEAD1 were reduced (P<0.05). The effect was more obvious in the Aca high dose group. However, there was no significant difference in each indicator between the Verteporfin group and the Aca high dose group. Conclusion Aca can inhibit angiogenesis and improve retinal pathological damage in DR rats, and its mechanism of action may be related to regulating the Hippo signaling pathway.

Key words: diabetic retinopathy, retinal neovascularization, acacin, Hippo signaling pathway

CLC Number:

R774.1

Figures/Tables 8

References 24

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组别	体质量/g	FBG/（mmol/L）
对照组	432.68±45.09	5.27±0.62
DR组	285.93±29.65^a	23.59±2.61^a
Aca低剂量组	358.76±36.92^b	15.62±1.61^b
Aca中剂量组	382.05±39.02^bc	10.07±1.14^bc
Aca高剂量组	417.25±42.83^bcd	6.37±0.72^bcd
Verteporfin组	403.86±41.09^bcd	6.48±0.68^bcd
F	28.295^＊＊	253.633^＊＊

组别	体质量/g	FBG/（mmol/L）
对照组	432.68±45.09	5.27±0.62
DR组	285.93±29.65^a	23.59±2.61^a
Aca低剂量组	358.76±36.92^b	15.62±1.61^b
Aca中剂量组	382.05±39.02^bc	10.07±1.14^bc
Aca高剂量组	417.25±42.83^bcd	6.37±0.72^bcd
Verteporfin组	403.86±41.09^bcd	6.48±0.68^bcd
F	28.295^＊＊	253.633^＊＊

组别	VEGF/（ng/L）	Ang-2/（μg/L）
对照组	105.32±10.38	6.38±0.66
DR组	163.58±17.14^a	11.92±1.24^a
Aca低剂量组	139.74±13.18^b	9.27±1.01^b
Aca中剂量组	125.07±12.49^bc	8.04±0.91^bc
Aca高剂量组	109.31±11.26^bcd	7.05±0.77^bc
Verteporfin组	110.83±11.75^bcd	7.48±0.78^bcd
F	30.569^＊＊	47.819^＊＊

组别	VEGF/（ng/L）	Ang-2/（μg/L）
对照组	105.32±10.38	6.38±0.66
DR组	163.58±17.14^a	11.92±1.24^a
Aca低剂量组	139.74±13.18^b	9.27±1.01^b
Aca中剂量组	125.07±12.49^bc	8.04±0.91^bc
Aca高剂量组	109.31±11.26^bcd	7.05±0.77^bc
Verteporfin组	110.83±11.75^bcd	7.48±0.78^bcd
F	30.569^＊＊	47.819^＊＊

组别	VEGF	HIF-1α	VCAM-1
对照组	0.42±0.09	0.58±0.06	0.38±0.04
DR组	1.43±0.15^a	1.26±0.12^a	1.36±0.18^a
Aca低剂量组	0.91±0.09^b	0.95±0.09^b	0.99±0.10^b
Aca中剂量组	0.73±0.07^bc	0.73±0.08^bc	0.61±0.07^bc
Aca高剂量组	0.52±0.06^bcd	0.61±0.07^bcd	0.45±0.05^bcd
Verteporfin组	0.59±0.06^bcd	0.63±0.08^bcd	0.43±0.04^bcd
F	95.456^＊＊	57.885^＊＊	103.997^＊＊