The inhibitory effect of capsaicin on streptozocin-induced apoptosis of rat retinal cells / 中华实验眼科杂志

ABSTRACT

Background Diabetes mellitus (DM) can provoke the apoptosis of retinal cells and downregulate the expression of calcitonin gene related peptide (CGRP) in the retina.Capsaicin promotes the release of CGRP and elicits protective effects on human organs.However,whether CGRP protects retinal cells in diabetic retinopathy (DR) is still unclear.Objective The study was designed to examine the effect of capsaicin on the apoptosis of retinal cells in diabetic rats and its relationship with CGRP.Methods Forty clean healthy adult male Sprague-Dawey rats were randomly divided into the diabetes group,capsaicin pretreated group,streptozocin (STZ)control group,capsaicin control group and plain control group,with 8 rats per group.The diabetic model was established by the intraperitoneal injection of 60 mg/kg in all rats except those of the plain control group.0.4 mL of a 1％ capsaicin injected at 20 mg/kg was subcutaneously injected for 3 consecutive days prior to model establishment in the capsaicin pretreated group,after which 1.2 mL of STZ was intraperitoneally injected on the fourth day.Rats from the STZ control group were administered intraperitoneally 1.2 mL of 0.1 mol/L,pH 4.5,citrate buffer.The capsaicin control group received subcutaneous injections of 0.4 mL of 1％ capsaicin at 20 mg/kg for 3 consecutive days,after which 1.2 mL of 0.1 mol/L,pH 4.5,citrate buffer was administered intraperitoneally.The rats were sacrificed at the tenth week after model establishment and retinal specimens were prepared for the apoptosis assay by TUNEL staining and the quantitative analysis of caspase-3 activity.Expression of CGRP in the retina and serum was detected using ELISA.The use of experimental animals followed the Regulations for the Administration of Affairs Concerning Experimental Animals by State Science and Technology Commission.Results Retinal cell apoptosis was mainly localized to the retinal ganglion cell (RGC) layer.The apoptosis rate of RGCs was (43.4±5.0)％ in the DR model group and (30.0±5.1)％ in the capsaicin pretreated group,showing a significant difference (t =5.930,P＜0.01).Compared with the DR model group and capsaicin pretreated group,the apoptosis rates of the DR control group (12.4±9.9) ％ and the capsaicin control group (17.6-±6.1) ％ were significantly lower (t =8.800,t =4.925,P＜0.01).The apoptosis rate of the plain control group was (16.2±6.9)％,exhibiting significant differences in comparison with the DR control group and capsaicin control group (t =-0.989,t =0.951,P＞0.05).The specific activity of caspase-3 was (2.19±0.86) in the DR model group and (1.96±0.56) in the capsaicin pretreated group,presenting a significant difference (t =-0.515,P＜0.05).Those of the DR control group and capsaicin control group were (1.47±0.14) and (0.74±0.27),respectively,with considerable decline in comparison with the DR model group and capsaicin pretreated group (t=2.142,t=2.797,P＜0.05).The retinal and serum CGRP levels were (424.4±44.2)and (148.8±39.1) ng/L,respectively,displaying significantly lower levels than (543.2±74.4) and (237.5±78.7) ng/L (t =3.070,2.359,P＜0.05) from the capsaicin pretreated group.Conclusions Apoptosis of retinal ganglion cells occurs in the STZ-induced diabetic rats.Pretreatment of capsaicin reduces retinal cell apoptosis,which may be associated with an increase of CGRP in the retina.