Li Na, Chen Ji-Lin, Sun Yi-Jian, Sun Jia-Fan, Wang Ting-Hua, Saik Amy Yi Hsan, Ong Alan Han-Kiat
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.
J Nat Med. 2025 Aug 8. doi: 10.1007/s11418-025-01935-1.
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.
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。