和厚朴酚调节mTOR/HIF-1α/VEGF信号通路对烟曲霉菌性角膜炎大鼠角膜组织损伤的影响OA
Impact of honokiol on corneal tissue damage in rats with Aspergillus fumigatus keratitis by regulating mTOR/HIF-1α/VEGF signaling pathway
目的 探究和厚朴酚(HNK)调节哺乳动物雷帕霉素靶蛋白(mTOR)/缺氧诱导因子-1α(HIF-1α)/血管内皮生长因子(VEGF)信号通路对烟曲霉菌性角膜炎(AFK)大鼠角膜组织损伤的影响.方法 随机将SD大鼠分为Ctrl组(5 µL DMSO溶剂)、模型组(5 µL DMSO溶剂)、低剂量HNK(L-HNK)组(2 µg/mL HNK)、中剂量HNK(M-HNK)组(4 µg/mL HNK)、高剂量HNK(H-HNK)组(8 µg/mL HNK)和mTOR激活剂+H-HNK组(10 mg/kg MHY1485+8 µg/mL HNK).除Ctrl组外,其余组均采用角膜接触镜法制备AFK大鼠模型.裂隙灯显微镜下观察、评估角膜组织损伤程度;平板菌落计数法评估角膜组织中烟曲霉菌含量;HE染色观察角膜组织病理学变化;ELISA检测角膜组织中炎症因子白细胞介素(IL)-1β、IL-6、肿瘤坏死因子α(TNF-α)水平;Western blot测定角膜组织中mTOR、HIF-1α、VEGF蛋白表达水平.结果 与Ctrl组比较,模型组大鼠角膜组织损伤评分、菌落数及IL-1β、TNF-α、IL-6表达增加(P<0.05),同时角膜胶原纤维排列紊乱、肿胀,大量炎性细胞浸润,坏死组织脱落;与模型组比较,L-HNK组、M-HNK组、H-HNK组大鼠角膜组织损伤评分、菌落数及IL-1β、TNF-α、IL-6表达减少(P<0.05),角膜组织上述变化均减轻,且H-HNK组减轻最为明显;与H-HNK组比较,mTOR激活剂+H-HNK组大鼠角膜组织损伤评分、菌落数及IL-1β、TNF-α、IL-6表达增加(P<0.05),角膜组织上述变化均加重.与Ctrl组比较,模型组大鼠角膜组织中mTOR、HIF-1α、VEGF蛋白表达增加(P<0.05);与模型组比较,H-HNK组大鼠角膜组织中上述蛋白表达均减少(P<0.05);与H-HNK组比较,mTOR激活剂+H-HNK组大鼠角膜组织中上述蛋白表达均增加(P<0.05).结论 HNK能够减轻AFK大鼠角膜组织损伤,可能通过抑制mTOR/HIF-1α/VEGF信号通路而实现.
Objective To explore the impact of honokiol(HNK)on corneal tissue damage in rats with aspergillus fumigatus keratitis(AFK)by regulating mammalian target of rapamycin(mTOR)/hypoxia inducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF)signaling pathway.Methods SD rats were randomly divided into the Ctrl group(5 µL DMSO solvent),model group(5 µL DMSO solvent),low-dose HNK(L-HNK)group(2 µg/mL HNK),medium-dose HNK(M-HNK)group(4 µg/mL HNK),high-dose HNK(H-HNK)group(8 µg/mL HNK),and mTOR activator+H-HNK group(10 mg/kg MHY1485+8 µg/mL HNK).Except for the Ctrl group,the AFK rat models were established by the corneal contact lens method in the other groups.Slit-lamp microscopy was used to observe and evaluate the degree of corneal tissue damage.Plate colony counting was employed to assess aspergillus fumigatus content in corneal tissues.HE staining was performed to examine the histopathological changes in corneal tissues.ELISA was utilized to detect the levels of inflammatory cytokines interleukin(IL)-1β,IL-6,and tumor necrosis factor alpha(TNF-α)in corneal tissues.And Western blot was conducted to determine the protein expression levels of mTOR,HIF-1α,and VEGF in corneal tissues.Results Compared with the Ctrl group,the model group showed increased corneal tissue injury scores,colony counts,and elevated expression of IL-1β,TNF-α,and IL-6(P<0.05),along with disordered collagen fiber arrangement,swelling,extensive inflammatory cell infiltration,and necrotic tissue shedding.In contrast to the model group,the L-HNK group,M-HNK group and H-HNK group exhibited reduced corneal tissue injury scores,colony counts,and decreased expression of IL-1β,TNF-α,and IL-6(P<0.05),along with alleviated corneal tissue changes,the most pronounced in the H-HNK group.Compared with the H-HNK group,the mTOR activator+H-HNK group showed increased corneal tissue injury scores,colony counts,and elevated expression of IL-1β,TNF-α,and IL-6(P<0.05),along with aggravated corneal tissue changes.Compared with the Ctrl group,the model group demonstrated increased protein expression of mTOR,HIF-1α,and VEGF in the corneal tissue(P<0.05).Compared with the model group,the H-HNK group exhibited decreased expression of these proteins(P<0.05).Compared with the H-HNK group,the mTOR activator+H-HNK group showed increased expression of these proteins(P<0.05).Conclusion HNK can alleviate corneal tissue damage in AFK rats,which may be achieved by inhibiting the mTOR/HIF-1α/VEGF signaling pathway.
王敏;霍楠;安伟乔;赵军波
邯郸市中心医院感染性疾病科,河北 邯郸 056001邯郸市中心医院眼科,河北 邯郸 056001邯郸市中心医院老年病科,河北 邯郸 056001邯郸市中心医院眼科,河北 邯郸 056001
医药卫生
和厚朴酚mTOR/HIF-1α/VEGF信号通路烟曲霉菌性角膜炎角膜组织损伤
honokiolmTOR/HIF-1α/VEGF signaling pathwayaspergillus fumigatus keratitiscorneal tissue damage
《局解手术学杂志》 2026 (2)
139-144,6
邯郸市科学技术研究与发展计划项目(21422083122)
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