Search

AIM: To investigate the therapeutic effect of finerenone (FIN) on diabetic retinopathy (DR) in rats, and to explore its possible mechanism. METHODS: (1) A total of 30 clean-grade male SD rats were selected. Ten rats were randomly selected as control group, and the remaining rats were DR rats. After successful modelling, the DR rats were randomly divided into DR group and DR+FIN group, with 10 rats in each group. The rats in DR+FIN group received 10 mg/kg FIN by intragastric administration every day, while those in DR group were given an equal volume of normal saline intragastrically for 3 months. Double immunofluorescence staining was used to examine the activation of deep retinal microglia, and the CellF system was used to analyze the numbers of retinal pericytes and acellular capillaries (AC). A multifocal retinal imaging system was used to examine the neuroretinal function of the rats, and RT-qPCR and Western blot were used to examine the mRNA and protein expression of related factors. (2) Rat microglia HAPI cells were cultured in vitro and randomly divided into normal glucose (NG) group, high glucose (HG) group, and HG+FIN group. The cells in NG group was cultured in NG nutrient solution (containing 1 g/L glucose), the cells in HG group was cultured in HG nutrient solution (containing 4. 5 g/L glucose), and the cells in HG+FIN group were cultured in HG medium for 24 h and treated with 10 mmol/L FIN. The migration of the cells in each group was examined by wound healing assay. RESULTS: (1) Compared with control group, the number of retinal pericytes, a-wave amplitude and b-wave amplitude were significantly decreased in DR group (P<0. 05), while the number of AC, ionized calcium-binding adaptor molecule 1 (Iba1)expression in deep retinal vascular layer, fasting blood glucose (FBG) level and the relative expression levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), IL-8, vascular cell adhesion molecule 1 (Vcam1), transforming growth factor-β1 (TGF-β1), C-C motif chemokine ligand 2 (Ccl-2) and mineralocorticoid receptor (MR) in the retinal tissue were significantly increased (P<0. 05). Compared with DR group, the number of retinal pericytes, a-wave amplitude and b-wave amplitude of the rats in DR+FIN group were significantly increased (P<0. 05), while the number of AC, Iba1 expression in deep retinal vascular layer, FBG level and the relative expression levels of IL-1β, TNF-α, IL-8, Vcam1, TGF-β1, Ccl-2 and MR in the retinal tissue were significantly decreased (P<0. 05). (2) Treatment with FIN significantly inhibited HAPI cell migration induced by HG. CONCLUSION: Treatment with FIN attenuates DR in rats by inhibiting microglial activation and inflammatory response. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To carry out preliminary investigation on the material bases of efficacy and mechanism of making prescriptions of “cholic acid-hyodeoxycholic acid” based on the network pharmacology. METHODS: Data of chemical compositions, action targets and related diseases of cholic acid and hyodeoxycholic acid were retrieved to construct “drug-composition-target-disease” network and conduct classified enrichment analysis of gene ontology ( GO ) and pathway enrichment analysis based on Kyoto encyclopedia of genes and genomes ( KEGG), so as to investigate the functional mechanism of “cholic acid-hyodeoxycholic acid”. RESULTS: The “drug-composition-target-disease” network contained 2 kinds of drugs, 2 kinds of active compositions, 6 related targets and 8 kinds of related diseases. Key target spots involved mineralocorticoid receptors, liver X receptor-α oxysterols and liver X receptor β oxysterols, key diseases included atherosclerosis and so on. (X) enrichment analysis contained 87 (X) items, of which 68 involved biological process, mainly included negative regulation of pinocytosis and positive regulation of triacylglycerol biosynthesis; 19 items involved molecular function, mainly included steroid hormone receptor activity and ligand-dependent nuclear receptor activity. KEGG pathway enrichment analysis contained 2 pathways, respectively were signaling pathways of insulin resistance and thyroid hormones. GONCLUSIONS: This study has preliminarily verified the basic pharmacological actions and the mechanism of “cholic acid-hyodeoxycholic acid”, and laid foundations for further revealing the functional mechanism. [ABSTRACT FROM AUTHOR]