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黄连素可减轻糖尿病视网膜病变中NLRP3及下游炎性小体效应蛋白的表达。

Berberine attenuates the expression of NLRP3 and downstream inflammasome effectors in diabetic retinopathy.

作者信息

Li Na, Chen Ji-Lin, Sun Yi-Jian, Sun Jia-Fan, Wang Ting-Hua, Saik Amy Yi Hsan, Ong Alan Han-Kiat

机构信息

M. Kandiah Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Bandar Sungai Long, Kajang, 43000, Selangor, Malaysia.

Institute of Neuroscience, Kunming Medical University, Kunming, 650500, China.

出版信息

J Nat Med. 2025 Aug 8. doi: 10.1007/s11418-025-01935-1.

DOI:10.1007/s11418-025-01935-1
PMID:40779223
Abstract

The objective of this study is to investigate the protective effects of berberine (BBR) on diabetic retinopathy (DR) and its regulatory mechanism on NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome pathway. DR rat model was established by Streptozotocin (STZ) injection and treated with BBR. Retinal structure was evaluated by Optical Coherence Tomography (OCT), Hematoxylin and Eosin (HE) staining, and immunofluorescence. NLRP3 pathway proteins were detected by Western blot (WB), and the effects were further studied using RNA interference. BBR significantly improved retinal structure in DR rats and decreased the expression of NLRP3, Cysteine-aspartic acid protease-1(Caspase-1), Gasdermin D (GSDMD), Interleukin-1 beta (IL-1β), and Interleukin-18 (IL-18) (p < 0.05). In an in vitro study using human RPE cells line, BBR administration improved cell viability and reduced RPE pyroptosis, while RNA interference of NLRP3 pathway enhanced BBR's protective effects. BBR ameliorates DR by inhibiting NLRP3 inflammasome-mediated pyroptosis pathway.

摘要

本研究的目的是探讨黄连素(BBR)对糖尿病视网膜病变(DR)的保护作用及其对含NOD样受体家族吡咯结构域3(NLRP3)炎性小体通路的调控机制。通过注射链脲佐菌素(STZ)建立DR大鼠模型并用BBR进行治疗。通过光学相干断层扫描(OCT)、苏木精和伊红(HE)染色以及免疫荧光评估视网膜结构。通过蛋白质免疫印迹法(WB)检测NLRP3通路蛋白,并使用RNA干扰进一步研究其作用效果。BBR显著改善了DR大鼠的视网膜结构,并降低了NLRP3、半胱天冬酶-1(Caspase-1)、gasdermin D(GSDMD)、白细胞介素-1β(IL-1β)和白细胞介素-18(IL-18)的表达(p<0.05)。在一项使用人视网膜色素上皮(RPE)细胞系的体外研究中,给予BBR可提高细胞活力并减少RPE细胞焦亡,而NLRP3通路的RNA干扰增强了BBR的保护作用。BBR通过抑制NLRP3炎性小体介导的焦亡途径改善DR。

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本文引用的文献

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Int J Mol Sci. 2024 Dec 30;26(1):246. doi: 10.3390/ijms26010246.
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Retinal OCT-Derived Texture Features as Potential Biomarkers for Early Diagnosis and Progression of Diabetic Retinopathy.视网膜光学相干断层扫描衍生的纹理特征作为糖尿病视网膜病变早期诊断和病情进展的潜在生物标志物
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HDAC6 mediates NLRP3 inflammasome activation in the pathogenesis of diabetic retinopathy.HDAC6在糖尿病视网膜病变的发病机制中介导NLRP3炎性小体激活。
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Review on the role of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome pathway in diabetes: mechanistic insights and therapeutic implications.核苷酸结合寡聚化结构域样受体蛋白 3(NLRP3)炎症小体通路在糖尿病中的作用研究进展:机制见解与治疗意义。
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Discovery of astragaloside IV against high glucose-induced apoptosis in retinal ganglion cells: Bioinformatics and in vitro studies.黄芪甲苷抑制高糖诱导的视网膜神经节细胞凋亡的作用机制:生物信息学和体外研究。
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