芝麻林素通过抑制p38 MAPK通路减轻糖尿病视网膜病变大鼠炎症反应及视网膜损伤OA

Objective To reveal the therapeutic effect of sesamolin(Ses)on diabetic retinopathy(DR)in rats and its effect on the inflammatory response mediated by p38 mitogen-activated protein kinase(MAPK)signaling pathway.Methods SPF-grade male SD rats were intraperitoneally injected with 35 mg·kg-1 streptozotocin to establish DR model rats.Rats were randomly divided into six groups:control group,DR group,10/20/40-Ses group(gavage of 10,20,and 40 mg·kg-1 Ses,respectively),and 40-Ses+Anisomycin group(gavage of 40 mg·kg-1Ses,and tail vein injection of 2 mg·kg-1 p38 MAPK agonist Anisomycin),with 12 rats in each group.The control group consisted of normally fed rats,while the other groups consisted of DR model rats.The intervention lasted 4 weeks.The fasting blood glucose(FBG)in rats was measured using a blood glucose meter;the expression levels of glycated hemoglobin(HbA1c)and fasting insulin(FINS)in rats were detected using the enzyme-linked immunosorbent assay(ELISA)kit.Hematoxylin-eosin and TUNEL staining were per-formed on the retina of rats to observe its morphology and cell apoptosis.ELISA and quantitative real-time polymerase chain reaction(qRT-PCR)were employed to detect the protein and mRNA expression levels of inflammation-related indicators in rat retina,including tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,IL-6,intercellular adhesion molecule-1(ICAM-1),and monocyte chemoattractant protein-1(MCP-1);qRT-PCR was used to detect the mRNA expression levels of Bax and Bcl-2 in rat retina;Western blot was applied to detect the expression levels of phosphorylated p38 MAPK and p65 nuclear factor-κB(p65 NF-NF)in rat retina.Results The retinal structure of rats in the control group was clear and intact,while the retinal structure of rats in the DR group was disordered and loose.The retinal structure of rats in the 10/20/40-Ses group improved,while the retinal lesions of rats in the 40-Ses+Anisomycin group worsened.Compared with the control group,the FPG,HbA1c,FINS,Bax mRNA expression levels,and the TUNEL+cell ratio in the rat retina in the DR group increased;the expression levels of TNF-α,IL-1β,IL-6,ICAM-1,and MCP-1 protein and mRNA,as well as the phosphorylation levels of p38 MAPK and p65 NF-κB,increased;the relative expression level of Bcl-2 mRNA decreased,and the differences were all statisti-cally significant(all P＜0.05).Compared with the DR group,the FPG,HbA1c,FINS,Bax mRNA expression levels,and the TUNEL+cell ratio in the retina of rats in the 10/20/40-Ses group decreased;the expression levels of TNF-α,IL-1β,IL-6,ICAM-1,and MCP-1 protein and mRNA,as well as the phosphorylation levels of p38 MAPK and p65 NF-κB,decreased;the relative expression level of Bcl-2 mRNA increased,and the differences were all statistically significant(all P＜0.05).Com-pared with the 40-Ses group,the FPG,HbA1c,FINS,Bax mRNA expression levels,and the TUNEL+cell ratio in the retina of rats in the 40-Ses+Anisomycin group increased;the expression levels of TNF-α,IL-1β,IL-6,ICAM-1,and MCP-1 protein and mRNA,as well as the phosphorylation levels of p38 MAPK and p65 NF-κB,increased;the relative expression level of Bcl-2 mRNA decreased,and the differences were all statistically significant(all P＜0.05).Conclusion Ses exerts thera-peutic effects by inhibiting the activation of the p38 MAPK signaling pathway in DR and reducing excessive inflammatory re-sponses.