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[摘要]
目的：研究骨髓间充质干细胞来源的外泌体(BMSC-Exos)对大鼠糖尿病视网膜病变(DR)的治疗作用，重点探讨其通过TLR4/NF-κB 信号通路调节氧化应激和炎症反应的能力。
方法：由链脲佐菌素(STZ)诱导的糖尿病SD大鼠被随机分为4组：第1组\〖正常+磷酸盐缓冲液(PBS)\〗、第2组(正常+外泌体)、第3组(DR+PBS)以及第4组(DR+外泌体)。模型建立后第8 wk，向玻璃体腔内注射BMSC-Exos或PBS。第16 wk采集视网膜组织进行组织学分析\〖苏木精-伊红(HE)染色\〗、细胞凋亡检测(TUNEL法)，并评估氧化应激标志物\〖8-OHdG、超氧化物歧化酶(SOD)和谷胱甘肽(GSH)\〗，并检测了炎症细胞因子\〖采用酶联免疫吸附测定(ELISA)检测白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)\〗水平，以及分子谱分析\〖通过定量聚合酶链反应(qPCR)检测TLR4，NF-κB，和VEGF表达水平\〗。
结果：BMSC-Exos显著抑制DR大鼠体内TLR4/NF-κB通路的激活(P<0.01)，同时伴有视网膜血管渗漏减少(伊文思蓝染色法，P<0.001)、细胞凋亡减少(TUNEL检测，P<0.05)以及氧化应激反应减轻(SOD和GSH升高、8-OHdG水平降低，P<0.05)。炎症细胞因子(IL-6和TNF-α)水平显著下降(P<0.01)。
结论：BMSC-Exos通过抑制TLR4/NF-κB信号通路，减轻氧化应激、炎症反应及微血管功能障碍，从而缓解DR。该研究为早期DR提供了新的治疗策略。
[Key word]
[Abstract]
AIM:To investigate the therapeutic effects of bone marrow mesenchymal stem cell-derived exosomes(BMSC-Exos)on diabetic retinopathy(DR)in rats, with a focus on their ability to modulate oxidative stress and inflammatory responses through the TLR4/NF-κB signaling pathway.
METHODS:Streptozotocin(STZ)-induced diabetic Sprague-Dawley(SD)rats were randomly divided into four groups: Group 1 \〖normal+phosphate-buffered saline(PBS)\〗, Group 2(normal+Exos), Group 3(DR+PBS), and Group 4(DR+Exos). At the 8th week after modeling, BMSC-Exos or PBS were injected intravitreally. Retinal tissues were collected at the 16th week for histological analysis \〖hematoxylin and eosin(HE)staining\〗, apoptosis detection(TUNEL). Oxidative stress markers \〖8-OHdG, superoxide dismutase(SOD), and glutathione(GSH)\〗 were assessed, and inflammatory cytokines \〖enzyme-linked immunosorbent assay(ELISA)for interleukin(IL)-6 and tumor necrosis factor-alpha(TNF-α)\〗, and molecular profiling \〖quantitative polymerase chain reaction(qPCR)for TLR4, NF-κB, and VEGF\〗 were measured.
RESULTS:The BMSC-Exos treatment significantly suppressed the activation of the TLR4/NF-κB pathway in DR rats(P<0.01), which was accompanied by reduced retinal vascular leakage(Evans blue assay, P<0.001), decreased apoptosis(TUNEL, P<0.05), and attenuated oxidative stress(elevated SOD and GSH, reduced 8-OHdG, P<0.05). The levels of inflammatory cytokines(IL-6 and TNF-α)were markedly decreased(P<0.01).
CONCLUSION:BMSC-Exos alleviate DR by suppressing the TLR4/NF-κB axis, thus reducing oxidative damage, inflammation, and microvascular dysfunction. This research offers a novel therapeutic approach for early-stage DR.
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