Effect and Mechanism of Marein on Diabetic Retinopathy
Effect and Mechanism of Marein on Diabetic Retinopathy
Zhipeng Song1,2, Jialiang Xin1,3, Xiaoli Wei1,2, Abula Zulipiya1,3, Kadier Kedireya1,2 and Xinmin Mao1,3*
ABSTRACT
This study was aimed at investigating the therapeutic effect of marein on db/db mice and its mechanism of action intervening in diabetic retinopathy. For in vivo experiment: 10 healthy db/m mice were used as the control group. Forty healthy db/db mice were randomly divided into the model, positive, ranibizumab and marein groups. There were 10 mice in each group. All mice were adaptively fed for one week. They were given the appropriate drugs by gavage. Tissue material was taken after 12 weeks. Haematoxylin-eosin (H&E) staining was used to detect the pathological changes of retinal tissue. Cell apoptosis was analysed by TUNEL staining. The expression of retinal proteins was detected by tissue immunofluorescence and immunohistochemical staining. The mRNA level of VEGF was detected by RT-qPCR. In the in vitro experiments, cell viability was detected by CCK-8 reagent. The expression of related proteins was detected by western blot. We found that marein can effectively reduce triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL) and blood glucose concentration (BGC) in db/db mice (P < 0.05). The results showed that marein could effectively alleviate diabetic retinopathy, such as oedema, cell body shrinkage, abnormal nuclear morphology, etc., and ultimately enhance retinal function. In vivo and in vitro experiments showed that after a period of intervention, marein regulates diabetic retinopathy by inhibiting the protein expressions of VEGF, PI3K, fibrin (FN) and spleen tyrosine kinase (SYK), and upregulating the level of E-cadherin, an epithelial marker. Molecular docking results showed that marein could integrate with VEGFA, PI3K and SYK, and the resulting conjugate was more potent than the positive drug metformin. Among the above factors, the combination effect of SYK and marein was the most ideal. To conclude marein can improve glucose and lipid metabolism disorders in db/db mice after a treatment period, so it has positive significance for the prevention and treatment of diabetes. Marein can act on SYK, VEGF and PI3K/AKT factors and change the expression of fibrosis and inflammatory factors in tissues by affecting their pathways. It can integrate with these and many other proteins, and the formed conjugates have a better therapeutic effect.
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