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| 基于NLRP3/Caspase-1信号通路探究槲寄生滴眼液对干眼症小鼠的治疗效果 |
| Exploring the therapeutic effect of mistletoe eye drops on dry eye mice based on the NLRP3/Caspase-1 signaling pathway |
| 投稿时间：2023-12-26 修订日期：2024-03-25 |
| DOI： |
| 中文关键词: 槲寄生滴眼液 干眼症小鼠 NOD样受体蛋白3 半胱天冬酶-1 泪液分泌量 结膜上皮 泪腺 |
| 英文关键词:Mistletoe eye drops Dry eye mice NOD like receptor protein 3 Caspase-1 Tear secretion volume Conjunctival epithelium lacrimal gland |
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| 中文摘要: |
| 目的:基于NOD样受体蛋白3(NLRP3)/半胱天冬酶-1(Caspase-1)信号通路探究槲寄生滴眼液对干眼症小鼠的治疗效果。方法:将干眼症模型小鼠(采用苯扎氯铵溶液滴眼造模)随机分成模型组(以生理盐水干预)、槲寄生滴眼液组(每次5 μL槲寄生滴眼液滴眼,每天2次)、NLRP3/Caspase-1通路抑制剂(VX-765)组(腹腔注射50 mg/kg的VX-765,每天1次)、槲寄生滴眼液+VX-765组(每次5 μL槲寄生滴眼液滴眼,每天2次,以及腹腔注射50 mg/kg的VX-765,每天1次)；12只/组。另取12只健康小鼠作为对照组(以生理盐水干预)。持续给药14天。酚红棉线测定泪液分泌情况；苏木素-伊红染色观察结膜上皮及泪腺组织病理改变情况；酶联免疫吸附法测定血清白细胞介素(IL)-18、IL-1β水平；荧光定量PCR和蛋白印迹法分别测定结膜上皮及泪腺组织中NLRP3、Caspase-1信使RNA(mRNA)和蛋白表达。结果:与对照组比较,模型组结膜上皮细胞排列紊乱,杯状细胞数量减少,固有层可见淋巴细胞浸润等病理损伤,泪腺组织呈现腺泡空泡样改变,结构不清晰,大小不均一,各小叶及腺泡间细胞排列紊乱等病理变化,泪液分泌量(被浸湿的长度)显著降低,血清IL-18、IL-1β、结膜上皮及泪腺组织NLRP3、Caspase-1 mRNA和蛋白表达显著升高(P＜0.05)。与模型组比较,槲寄生滴眼液组、VX-765组结膜上皮及泪腺组织上述病理损伤减轻,泪液分泌量(被浸湿的长度)显著升高,血清IL-18、IL-1β、结膜上皮及泪腺组织NLRP3、Caspase-1 mRNA和蛋白表达显著降低(P＜0.05)。与槲寄生滴眼液组和VX-765组比较,槲寄生滴眼液+VX-765组结膜上皮及泪腺组织上述病理损伤进一步减轻,泪液分泌量(被浸湿的长度)显著升高,血清IL-18、IL-1β、结膜上皮及泪腺组织NLRP3、Caspase-1 mRNA和蛋白表达显著降低(P＜0.05)。结论:槲寄生滴眼液可减轻干眼症小鼠结膜上皮及泪腺组织损伤,改善其干眼症状和炎症,可能通过下调NLRP3/Caspase-1信号通路实现。 |
| 英文摘要: |
| Objective: To investigate the therapeutic effect of mistletoe eye drops on dry eye mice based on the NOD like receptor protein 3 (NLRP3)/Caspase-1 signaling pathway. Methods: Dry eye model mice (eye drops modeling with benzalkonium chloride solution) were randomly divided into model group (intervention with normal saline), mistletoe eye drops group (5 μL mistletoe eye drops each time, twice a day), NLRP3/Caspase-1 pathway inhibitor (VX-765) group (intraperitoneally injected with 50 mg/kg of VX-765, once a day), mistletoe eye drops+VX-765 group (5 μL mistletoe eye drops twice a day, and 50 mg/kg VX-765 intraperitoneally injected once a day); 12 pieces/group. Another 12 healthy mice were selected as control group (with normal saline intervention). Continued administration for 14 days. The tear secretion was measured with phenol red cotton thread; the pathological changes of conjunctival epithelium and lacrimal gland tissues were observed by hematoxylin-eosin staining; serum levels of interleukin (IL)-18 and IL-1β were determined by enzyme-linked immunosorbent assay; the messenger RNA (mRNA) and protein expressions of NLRP3 and Caspase-1 in conjunctival epithelium and lacrimal gland tissues were determined by fluorescence quantitative PCR and western blot. Results: Compared with control group, the model group showed disordered arrangement of conjunctival epithelial cells, decreased number of goblet cells, and pathological damage such as lymphocyte infiltration in the lamina propria, the lacrimal gland tissue showed acinar vacuolar like changes with unclear structure and uneven size, the arrangement of cells between lobules and acini was disordered, and the volume of tear secretion (length of being soaked) was significantly reduced, the serum IL-18, IL-1β, NLRP3, Caspase-1 mRNA and protein expressions in conjunctival epithelium and lacrimal gland tissues were significantly increased (P<0.05). Compared with model group, the above pathological injuries of conjunctival epithelium and lacrimal gland tissues were reduced in mistletoe eye drops group and VX-765 group, and the volume of tear secretion (length of being soaked) was significantly increased, the serum IL-18, IL-1β, NLRP3, Caspase-1 mRNA and protein expressions in conjunctival epithelium and lacrimal gland tissues were significantly decreased (P<0.05). Compared with mistletoe eye drops group and VX-765 group, the above pathological injuries of conjunctival epithelium and lacrimal gland tissues in mistletoe eye drops+VX-765 group were further reduced, and the volume of tear secretion (length of being soaked) was significantly increased, the serum IL-18, IL-1β, NLRP3, Caspase-1 mRNA and protein expressions in conjunctival epithelium and lacrimal gland tissues were significantly decreased (P<0.05). Conclusions: Mistletoe eye drops can alleviate damage to conjunctival epithelium and lacrimal gland tissue in mice with dry eye syndrome, improve dry eye symptoms and inflammation, possibly by downregulating the NLRP3/Caspase-1 signaling pathway. |
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