The Impacts of Carnosic Acid on Optic Nerve Injury in Glaucoma Rats by Adjusting Keap1-Nrf2 Pathway
HE Liye1,2,3, ZHANG Haijiang1,2,3*
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 sto chastically 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 f luorescence gold retrograde method was used to label rat RGCs (retinal ganglion cells). Retinal capture was per formed 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 apopto sis 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 surviv ing 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.
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