【摘要】 该研究探讨鼠尾草酸(CA)对青光眼大鼠视神经损伤及Keap1-Nrf2通路的影响。首先,构建青光眼大鼠模型;将造模成功大鼠随机分为模型组(Model组),鼠尾草酸低、高剂量处理组(CA-L、CA-H组),鼠尾草酸高剂量处理+Nrf2抑制剂组(CA-H+ML385),每组18只,另取18只健康大鼠作为对照组(Control组);检测各组大鼠眼压; ELISA检测视网膜氧化应激水平; HE染色观察视网膜病理损伤;荧光金逆行标记大鼠视网膜神经节细胞(RGCs);视网膜捕片观察RGCs细胞并计数; TUNEL染色观察RGCs细胞凋亡; Western blot检测视网膜组织Keap1-Nrf2通路及凋亡相关蛋白表达情况。结果显示, Model组较Control组大鼠眼压, ROS、MDA水平, RGCs凋亡率, Bax/Bcl-2、Cleaved-caspase-3/caspase-3值, Keap1表达水平升高,神经纤维层厚度, RGCs存活数目, SOD活性,Nrf2、HO-1表达水平降低(P<0.05); CA-L、CA-H组较Model组大鼠眼压, ROS、MDA水平, RGCs凋亡率, Bax/Bcl-2、Cleaved-caspase-3/caspase-3值, Keap1表达水平降低,神经纤维层厚度, RGCs存活数目, SOD活性, Nrf2、HO-1表达水平升高(P<0.05); CA-H+ML385组较CA-H组大鼠眼压, ROS、MDA水平, RGCs凋亡率, Bax/Bcl-2、Cleaved-caspase-3/caspase-3值, Keap1表达水平升高,神经纤维层厚度, RGCs存活数目, SOD活性, Nrf2、HO-1表达水平降低(P<0.05)。总之,鼠尾草酸可减轻青光眼大鼠神经损伤,与调节Keap1-Nrf2通路有关。更多还原

【Abstract】 This study explores the impacts of CA(carnosic acid) on optic nerve injury in glaucomatous rats and the Keap1-Nrf2 pathway. Firstly, establish a rat model of glaucoma, and successfully modeled rats were stochastically assigned into a Model group, CA-L, CA-H groups(low and high-dose carnosic acid treatment groups), and CA-H+ML385 group(high-dose carnosic acid treatment+Nrf2 inhibitor), each with 18 rats. Additionally, 18 healthy rats were designated as Control group. The intraocular pressure of rats in each group was measured. ELISA was used to detect retinal oxidative stress levels. HE staining was used to observe retinal pathological damage. The fluorescence gold retrograde method was used to label rat RGCs(retinal ganglion cells). Retinal capture was performed to observe and count RGCs cells. TUNEL staining was used to observe apoptosis of RGCs cells. Western blot was performed to detect the Keap1-Nrf2 pathway and apoptosis related proteins in retinal tissue. The results showed that compared with the Control group, the levels of intraocular pressure, ROS, MDA, as well as the apoptosis rate of RGCs, the ratios of Bax/Bcl-2, Cleaved-caspase-3/caspase-3, and Keap1 expression levels in the Model group were all increased, while the thickness of the nerve fiber layer, the number of surviving RGCs, the activity of SOD, the expressions levels of Nrf2 and HO-1 were all decreased(P<0.05). Compared with the Model group, the levels of intraocular pressure, ROS, MDA, as well as the apoptosis rate of RGCs, the ratios of Bax/Bcl-2, Cleaved-caspase-3/caspase-3, and Keap1 expression levels in the CA-L and CA-H groups decreased, while the thickness of the nerve fiber layer, the number of surviving RGCs, the activity of SOD, and the expressions levels of Nrf2 and HO-1 increased(P<0.05). Compared with the CA-H group, the levels of intraocular pressure, ROS, MDA, as well as the apoptosis rate of RGCs, the ratios of Bax/Bcl-2, Cleaved-caspase-3/caspase-3, and Keap1 expression levels were all increased in the CA-H+ML385 group, while the thickness of the nerve fiber layer, the number of surviving RGCs, the activity of SOD, the expression levels of Nrf2 and HO-1 were all decreased(P<0.05). In conclusion, carnosic acid can improve nerve damage in glaucoma rats, which is related to adjusting Keap1-Nrf2 pathway.更多还原