虎杖苷通过AMPK/Nrf2途径调控糖尿病大鼠伤口愈合和血管生成的机制研究  

The mechanism of polydatin regulating wound healing and angiogenesis in diabetic rats through AMPK/Nrf2 pathway

作　　者：童海江[1] 周恺骅 夏伟仁[1] 王社梁[1] 孙海燕[1] 王亚玲[1] 陈立新 TONG Haijiang;ZHOU Kaihua;XIA Weiren;WANG Sheliang;SUN Haiyan;WANG Yaling;CHEN Lixin(Shaoxing Second Hospital Medical Community General Hospital,Shaoxing,312000;Chengqin Biotechnology(Shanghai)Co.LTD,Shanghai,200030)

机构地区：[1]绍兴第二医院医共体总院,浙江绍兴312000 [2]诚勤生物科技(上海)有限公司,上海200030

出　　处：《浙江中医杂志》2024年第3期190-193,共4页Zhejiang Journal of Traditional Chinese Medicine

基　　金：浙江省中医药科技计划项目虎杖甙调控miR-128-3p/SIRT1/自噬对糖尿病伤口愈合的促进作用研究,编号:2021ZB309。

摘　　要：目的:基于AMPK/Nrf2途径探讨虎杖苷(PD)对糖尿病(DM)大鼠伤口愈合和血管生成的作用机制。方法:建立DM大鼠模型,将45只DM大鼠随机分为DM组、DM+PD组和DM+PD+ML385组(n=15),另取15只健康大鼠作为对照组,建立伤口愈合受损的模型,DM+PD组大鼠予PD灌胃(20mg/kg),DM+PD+ML385组大鼠在PD的基础上腹腔注射ML385抑制AMPK/Nrf2通路(30mg/kg)。比较各组大鼠伤口愈合情况,通过免疫组化染色检测分析微血管密度,Westernblot及RT-qPCR分析转化生长因子β1(TGF-β1)、血管内皮生长因子(VEGF)以及AMPK/Nrf2通路转录和翻译水平。结果:四组小鼠的上述指标比较差异显著(P<0.05)。DM组的伤口愈合百分比、生成血管数目、TGF-β1和VEGF蛋白水平、AMPK和Nrf2 mRNA和蛋白表达水平显著低于对照组(P<0.05)。DM+PD组的伤口愈合百分比、生成血管数目、TGF-β1和VEGF蛋白水平、AMPK和Nrf2mRNA和蛋白表达水平显著高于DM组(P<0.05)。DM+PD+ML385组的伤口愈合百分比、生成血管数目、TGF-β1和VEGF蛋白水平、AMPK和Nrf2 mRNA和蛋白表达水平显著低于DM+PD组而显著高于DM组(P<0.05)。结论:PD可能通过调控AMPK/Nrf2通路诱导血管生成,进而促进DM模型大鼠的伤口愈合。Objective:To investigate the mechanism of polydatin on wound healing and angiogenesis in rats with diabetes mellitus(DM)based on AMPK/Nrf2 pathway.Methods:The DM rat model was established,and 45 DM rats were randomly divided into DM group,DM+PD group and DM+PD+ML385 group(n=15).Another 15 healthy rats were selected as the control group,and a model with impaired wound healing was established.Rats in DM+PD group were given PD administration(20mg/kg).Rats in DM+PD+ML385 group were intraperitoneally injected with ML385 on the basis of PD to inhibit AMPK/Nrf2 pathway(30mg/kg).Wound healing of rats in each group was compared.Microvascular density was analyzed by immunohistochemical staining,and transcription and translation levels of TGF-β1,VEGF and AMPK/Nrf2 pathways were analyzed by Western blot and RTqPCR.Results:There were significant differences in the above indexes among the four groups(P<0.05).Wound healing percentage,number of blood vessels,TGF-β1 and VEGF protein levels,mRNA and protein expression levels of AMPK and Nrf2 in DM group were significantly lower than those in control group(P<0.05).Wound healing percentage,number of blood vessels,TGF-β1and VEGF protein levels,mRNA and protein expression levels of AMPK and Nrf2 in DM+PD group were significantly higher than those in DM group(P<0.05).Wound healing percentage,number of blood vessels,TGF-β1 and VEGF protein levels,mRNA and protein expression levels of AMPK and Nrf2 in DM+PD+ML385 group were significantly lower than those in DM+PD group but significantly higher than those in DM group(P<0.05).Conclusion:PD may induce angiogenesis by regulating AMPK/Nrf2 pathway,thus promoting wound healing in DM model rats.

关 键 词：虎杖苷 糖尿病 伤口愈合 血管生成 AMPK/Nrf2 

分 类 号：R285.5[医药卫生—中药学]