三七总皂苷对碘酸钠所致视网膜损伤的保护作用及机制研究

Study on protective effect and mechanism of panax notoginseng saponins on retina injury induced by sodium iodate

目的探讨三七总皂苷(PNS)对碘酸钠所致视网膜损伤的保护作用及作用机制。方法75只C57BL/6雄性小鼠,分为正常组、模型组和PNS低(50 mg·kg^(-1))、中(100 mg·kg^(-1))、高剂量(200 mg·kg^(-1))组,每组15只。PNS治疗组小鼠按相应的剂量预保护7 d后,模型组和PNS治疗组小鼠以25 mg·kg^(-1)剂量尾静脉注射碘酸钠溶液,建立小鼠视网膜损伤模型。PNS治疗组继续灌胃给药28 d。采用眼底照相及OCT检测小鼠视网膜损伤情况;FFA法观察视网膜血管渗漏情况;HE染色观察小鼠视网膜组织形态变化;试剂盒检测血清中抗氧化指标水平,ELISA法检测小鼠血清中炎性细胞因子的表达水平;Western blot法检测各组小鼠视网膜组织细胞核内Nrf2、核内NF-κB p65、HO-1与NQO1蛋白的表达情况。结果与正常组比较,模型组小鼠视网膜出现大量的黄白色类似玻璃膜疣状沉积,视网膜相对厚度下降(P<0.01),视网膜血管出现大面积的渗漏;血清中SOD活力与GSH含量下降(P<0.01),MDA、IL-6、TNF-α与IL-1β含量上升(P<0.01)。与模型组相比,PNS治疗组小鼠视网膜黄白色类似玻璃膜疣状沉积减少,视网膜相对厚度增加(P<0.05)、血管渗漏面积减少;血清中SOD活力与GSH含量上升(P<0.01),MDA、IL-6、TNF-α与IL-1β的含量下降(P<0.05);视网膜组织细胞核内Nrf2、HO-1和NQO1的蛋白表达上升(P<0.05),核内NF-κB p65的蛋白表达减少(P<0.05)。结论PNS可通过抗氧化应激与抗炎作用减弱碘酸钠诱导的视网膜损伤,其机制可能与PNS激活Nrf2/HO-1信号通路有关。

Objective To explore the protective effect and mechanism of panax notoginseng saponins(PNS)on retinal injury caused by sodium iodate.Methods 75 C57BL/6 male mice were divided into normal group,model group,and PNS low(50 mg·kg^(-1)),middle(100 mg·kg^(-1)),High-dose(200 mg·kg^(-1))groups,15 mice per group.After 7 days of pre-protection of the mice in the PNS groups according to the corresponding dose,the mice in the model group and the PNS treatment groups were injected with sodium iodate solution 25 mg·kg^(-1)through the tail vein to establish a mice model of retinal injury.The PNS treatment groups continued to intragastric administration for 28 days after modeling.Fundus photography and OCT were used to detect the retinal damage of mice;FFA was used to observe the leakage of retinal vascular;HE staining was used to observe the pathological changes of mice retinal;kits were used to detect the level of antioxidant index in serum of mice,ELISA were used to detect the serum level of inflammatory factors;Western blot was used to detect the expression of Nrf2(nucleus),NF-κB p65(nucleus),HO-1,NQO1 proteins of retinal tissues.Results Compared with the control group,a large number of yellow white drusen-like deposits appeared in the retina,the thickness of the retina was decreased(P<0.01),and extensive leakage of retinal blood vessels,the activity of SOD and the content of GSH were decreased in the serum(P<0.01),and the content of MDA,IL-6,TNF-α and IL-1β were increased in the model group(P<0.01).The yellow white drusen-like deposits in the retina of the administration groups were decreased,the thickness of the retina increased(P<0.05),and the blood vessel leakage was reduced;the SOD activity and the content of GSH in the serum increased(P<0.01),and the content of MDA,IL-6,TNF-α and IL-1β decreased(P<0.05);the protein expression of Nrf2 in the nucleus and HO-1 and NQO1 in the retinal tissue were increased(P<0.05),and the protein expression of NF-κB p65 in the nucleus was decreased(P<0.05).Conclusion PNS could attenuate sodium iodate-induced retinal damage through anti-oxidative stress and anti-inflammatory effects.The mechanism might be related to the activation of Nrf2/HO-1 signaling pathway by PNS.