摘要
目的 探讨柚皮素调节酪氨酸蛋白激酶2(janus kinase 2,JAK2)/信号转导与转MCP-1录激活因子 3(signal transducer and activator of transcription 3,STAT3)/细胞因子信号转导抑制因子-1(suppressor of cytokine signaling 1,SOCS1)信号通路对糖尿病视网膜病变(diabetes retinopathy,DR)大鼠的治疗作用.方法 构建DR大鼠模型,并随机分为DR组、柚皮素组、激活剂组、柚皮素+激活剂组,以正常大鼠为对照组,各组按照相应分组干预后,检测大鼠血糖、糖化血红蛋白;分离视网膜组织,检测白细胞介素(interleukin-6,IL)-6、IL-1β、谷胱甘肽(glutathione,GSH)、过氧化氢酶(catalase,CAT),检测大鼠病理变化及血视网膜血管屏障通透性,并对视网膜组织黏附因子(vascular cell adhesion molecule 1,VCAM-1)、抗血管内皮生长因子(vascular endothelial growth factor,VEGF)mRNA及JAK2/STAT3/SOCS1通路相关蛋白进行检测.结果 对照组血糖为(5.16±0.53)mmoL、糖化血红蛋白为(4.26±0.45)％、IL-6 为(63.11±6.35)pg/mL、IL-1β 为(23.11±2.38)pg/mL、伊文思蓝(EB)含量为(4.72±0.49)ng/mg、VCAM-1为 1.02±0.11、VEGF mRNA表达为0.93±0.10、p-JAK2/JAK2为(0.24±0.03)、p-STAT3/STAT3 为(0.19±0.02)、GSH 为(17.62±1.81)nmoUmg、CAT 为(11.68±1.19)IU/mg、SOCS1 为 1.44±0.16,DR 组血糖为(18.85±1.89)mmoL、糖化血红蛋白为(11.62±1.18)％、IL-6 为(89.17±8.99)pg/mL、IL-1β为(52.11±5.28)pg/mL、EB 含量为(10.24±1.08)ng/mg、VCAM-1 为 1.56±0.16、VEGF mRNA表达为 1.61±0.18、p-JAK2/JAK2 为 0.55±0.06、p-STAT3/STAT3 表达为 0.47±0.05,均较对照组降低(P＜0.05);DR 组 GSH 为(8.27±0.88)nmoUmg)、CAT 为(6.85±0.71)IU/mg、SOCS1为 0.86±0.09,均较对照组增加(P＜0.05).柚皮素组血糖为(13.11±1.34)mmoL、糖化血红蛋白为(7.36±0.76)％.IL-6为(67.08±6.75)pg/mL、IL-1β为(31.61±3.22)pg/mL、EB含量为(6.15±0.63)ng/mg、VCAM-1为 1.15±0.12、VEGF mRNA 表达为 1.17±0.12、p-JAK2/JAK2 为 0.29±0.03、p-STAT3/STAT3 为 0.21±0.03,均较 DR 组降低(P＜0.05),GSH 为(15.22±1.59)nmoUmg、CAT为(10.95±1.11)IU/mg、SOCSI表达为1.37±0.15,均较DR组升高(P＜0.05);激活剂逆转了柚皮素对DR大鼠的保护作用.结论 柚皮素调节JAK2/STAT3/SOCS1信号通路可改善DR大鼠损伤.
Abstract
Objective To investigate the therapeutic effect of naringenin on diabetes retinopathy(DR)rats by regulating Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)/suppressor of cytokine signaling1(SOCS1)signaling pathway.Methods A DR rat model was constructed and randomly sepa-rated into DR group,naringenin group,activator group,and naringenin+activator group,with normal rats as the con-trol group.After intervention according to corresponding groups,blood glucose and glycosylated hemoglobin of rats were detected.Retinal tissue was separated,and interleukin-6(IL-6),IL-1 β,glutathione(GSH),and catalase(CAT)were detected.The pathological changes in rats and blood retinal vascular barrier permeability were detect-ed,and the retinal tissue adhesion factor 1(VCAM-1),anti vascular endothelial growth factor(VEGF)mRNA,and JAK2/STAT3/SOCS1 pathway related proteins were detected.Results In the control group,blood glucose lev-els were(5.16±0.53)mmoL,glycosylated hemoglobin(4.26±0.45)％,IL-6(63.11±6.35)pg/mL,IL-1β(23.11±2.38)pg/mL,Evans blue(EB)content(4.72±0.49)ng/mg,VCAM-1(1.02±0.11),VEGF mRNA expression(0.93±0.10),p-JAK2/JAK2(0.24±0.03),p-STAT3/STAT3(0.19±0.02),GSH(17.62±1.81)nmoL/mg,CAT(11.68±1.19)IU/mg,and SOCS1 expression 1.44±0.16;while in DR group,blood glucose were(18.85±1.89)mmoL,HBA1c(11.62±1.18)％,IL-6(89.17±8.99)pg/mL,IL-1β(52.11±5.28)pg/mL,EB(10.24±1.08)ng/mg,VCAM-1 1.56±0.16,VEGF 1.61±0.18,P-JAK2/JAK2 0.55±0.06 and P-STAT3/STAT3 0.47±0.05,all decreased compared with that of the control group(P＜0.05).The expressions of GSH were(8.27±0.88)nmoUmg,CAT(6.85±0.71)IU/mg and SOCS1 0.86±0.09 in group DR,all increased compared with those of the control group(P＜0.05).In naringin group,blood glucose was(13.11±1.34)mmoL,HBA1c(7.36±0.76)％,IL-6(67.08±6.75)pg/mL,IL-1β(31.61±3.22)pg/mL,EB content was(6.15±0.63)ng/mg,VCAM-1 1.15±0.12,VEGF mRNA expression 1.17±0.12,P-JAK2/JAK2 0.29±0.03,and P-STAT3/STAT3 0.21±0.03,all lower than those in DR Group(P＜0.05).However,the expressions of GSH were(15.22±1.59)nmoUmg,CAT(10.95±1.1 1)IU/mg,and SOCS1(1.37±0.15),all higher than those of DR group(P＜0.05).The activator reversed the protective effect of naringenin on DR Rats.Conclusion Naringenin improves DR rat injury by regulating the JAK2/STAT3/SOCS1 signaling pathway.
NETL
NSTL
万方数据