Preventive and therapeutic effects of resveratrol on lens opacification in diabetic rats and its mechanism

To investigate the preventive and therapeutic effects of resveratrol on lens opacification in diabetic rats and its biological mechanism.

Fifty 8-week-old healthy male SPF grade SD rats were selected and randomly divided into blank control group, model group, gliclazide group, low-dose resveratrol group and high-dose resveratrol group according to their body weight, with 10 rats in each group.The diabetes model was established by intraperitoneal injection of streptozotocin in model group, gliclazide group, low-dose resveratrol group and high-dose resveratrol group.On the third day after modeling, rats in gliclazide group was gavaged with 2 mg/(kg·d) gliclazide suspension, and rats in low-dose and high-dose resveratrol groups were gavaged with 20 and 40 mg/(kg·d) resveratrol, respectively, for four weeks.Rats in blank control group and model group were gavaged with the same volume of normal saline once a day, also for four weeks.After the diabetes model was established, there were 10 rats in blank control group and 9 rats in the other four groups.The fasting blood glucose concentration of the rats was measured with a blood glucose meter.The concentrations of fasting insulin, superoxide dismutase (SOD) 1, SOD2, SOD3, and glutathione peroxidase (GPX1) were determined by enzyme-linked immunosorbent assay.Lens opacification after treatment was observed by slit lamp microscopy.Morphologic changes in lens cells were examined by hematoxylin-eosin staining.Apoptosis of lens epithelial cells (LECs) was detected using TUNEL.The relative expressions of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins in lens tissues were determined by Western blot.The study protocol was approved by the Welfare Ethics Committee of Experimental Animal of Zhengzhou University (No.IACYC2019-02).

Fasting blood glucose concentration, fasting insulin level, and apoptosis rate of LECs were increased and the concentrations of SOD1, SOD2, SOD3, and GPX1 were decreased in model group in comparison with blank control group, and the differences were statistically significant (all at P<0.05). Fasting blood glucose concentration, fasting insulin level, and apoptosis rate of LECs were decreased and the concentrations of SOD1, SOD2, SOD3, and GPX1 were increased in gliclazide group, low-dose resveratrol group, and high-dose resveratrol group compared with model group, and the differences were statistically significant (all at P<0.05). Fasting blood glucose concentration, fasting insulin level, and apoptosis rate of LECs were decreased and the concentrations of SOD1, SOD2, SOD3, and GPX1 were increased in gliclazide group and high-dose resveratrol group compared with low-dose resveratrol group, and the differences were statistically significant (all at P<0.05). The proportions of grade 0, 1 and 2 lens opacities after treatment were 100.00%, 0.00% and 0.00% in blank control group, 0.00%, 66.67% and 33.33% in model group, 77.78%, 22.22% and 0.00% in gliclazide group, 22.22%, 44.44% and 33.33% in low-dose resveratrol group, and 66.67%, 33.33% and 0.00% in high-dose resveratrol group, respectively, with a statistically significant difference (H=7.514, P<0.001). Compared with model group, lens opacification was less severe in blank control group, gliclazide group, low-dose resveratrol group, and high-dose resveratrol group, with statistically significant differences (all at P<0.05). Lens opacification was less severe in gliclazide group and high-dose resveratrol group compared with low-dose resveratrol group, showing statistically significant differences (both at P<0.05). Compared with model group, there were fewer abnormal changes of lens cells and sub-organelles in gliclazide group, low-dose resveratrol group and high-dose resveratrol group, and the abnormalities in gliclazide group and high-dose resveratrol group were slighter.Compared with model group, the relative expression levels of Nrf2 and HO-1 were higher in blank control group, gliclazide group, low-dose resveratrol group, and high-dose resveratrol group, with statistically significant differences (all at P<0.05). The relative expression levels of Nrf2 and HO-1 were higher in gliclazide group and high-dose resveratrol group compared with low-dose resveratrol group, showing statistically significant differences (both at P<0.05).

Resveratrol can reduce lens opacification in diabetic rats and its mechanism may be related to the regulation of the Nrf2/HO-1 signaling pathway by exerting antioxidative stress effects.