AKT/FoxO3a通路在白藜芦醇抑制大鼠肾脏间质纤维化中的作用  

Effect of AKT/FoxO3a pathway in resveratrol inhibiting renal interstitial fibrosis in rats

作　　者：孙荣嵘 冯小华 王婷婷[1] 刘楠 张瑞城 钟良宝[1] SUN Rongrong;FENG Xiaohua;WANG Tingting;LIU Nan;ZHANG Ruicheng;ZHONG Liangbao(Department of Rheumatology and Immunology,First Affiliated Hospital of Hainan Medical College,Haikou 570206,China)

机构地区：[1]海南医学院第一附属医院肾内风湿免疫科

出　　处：《药物评价研究》2019年第11期2165-2168,共4页Drug Evaluation Research

基　　金：海南省自然科学基金(20158333)

摘　　要：目的探讨蛋白激酶B (Akt)/FoxO3a通路在白藜芦醇抑制肾脏纤维化中的作用。方法将55只SD大鼠随机分为假手术组(10只)和造模组(45只),采用单侧输尿管梗阻法构建大鼠肾间质纤维化模型,45只造模SD大鼠术后随机分为模型组和白藜芦醇(20、40 mg/kg)干预组,每组15只。干预组大鼠于术后ig白藜芦醇20、40 mg/kg,1次/d,持续2周。模型组大鼠ig等量生理盐水。HE、Masson染色观察肾组织病理变化,免疫组化检测α-SMA阳性细胞,Western blot检测Akt、p-Akt、FoxO3a、p-FoxO3a蛋白。结果假手术组、模型组、白藜芦醇20 mg/kg干预组和白藜芦醇40 mg/kg干预组肾小管损伤病理评分分别为(0.36±0.05)、(4.07±0.53)、(3.92±0.48)和(3.21±0.35),其中白藜芦醇20 mg/kg干预组与模型组间无显著性差异,假手术组评分显著低于白藜芦醇干预组(P<0.05),白藜芦醇40 mg/kg干预组又显著低于造模对照组(P<0.05)。假手术组、模型组和白藜芦醇40 mg/kg干预组α-SMA阳性细胞比例分别为(3.84±0.62)%、(52.36±14.27)%和(26.15±4.63)%,3组间具有显著性差异(P<0.01)。FoxO3a和Akt蛋白表达三组间无显著性差异,p-Akt和pFoxO3a蛋白表达在模型组SD大鼠显著减低,但白藜芦醇40 mg/kg干预组p-Akt和p-FoxO3a蛋白表达高于模型组,低于假手术组。结论白藜芦醇可以减低p-Akt和p-FoxO3a蛋白表达,发挥抗肾间质纤维化作用。Objective To investigate the role of protein kinase B(Akt)/FoxO3 a pathway in the inhibition of renal fibrosis by resveratrol.Methods 55 SD rats were devided into sham-operated group(10 rats) and model group(45 rats).The rat model of renal interstitial fibrosis was established by unilateral ureteral obstruction.45 SD rats were randomly divided into model group and resveratrol(20,40 mg/kg) intervention group,and each group had 15 rats.The rats in the intervention group were ig 20,40 mg/kg resveratrol,once daily for 2 weeks.The rats in model group received the same amount of normal saline.HE and Masson staining was used to observe renal pathological change.a-SMA positive cells were detected by immunohistochemical staining.Akt,p-Akt,FoxO3 a,and p-FoxO3 a were detected by Western blot analysis.Results The pathological scores of renal tubular injury in shamoperated group,model group,resveratrol 20 mg/kg intervention group,and resveratrol 40 mg/kg intervention group were(0.36±0.05),(4.07±0.53),(3.92±0.48),and(3.21±0.35),respectively.There was no significant difference between resveratrol 20 mg/kg intervention group and model control group.The scores in sham-operated group was significantly lower than that in the resveratrol intervention group(P <0.05),and resveratrol(40 mg/kg) intervention group was lower than that in model control group(P <0.05).The percentage of alpha-SMA positive cells in sham-operated group,model group,and resveratrol 40 mg/kg intervention group was(3.84±0.62)%,(52.36±14.27)%,and(26.15±4.63)%,respectively.There was significant difference among the three groups(P <0.01).There was no significant difference of FoxO3 a and Akt protein expression among the three groups.The p-Akt and p-FoxO3 a protein expression in model group SD rats was decreased significantly.However,the expression of p-Akt and p-FoxO3 a protein in resveratrol 40 mg/kg intervention group was higher than that in model control group,and lower than that in sham-operated group.Conclusion Resveratrol can reduce the expression of p-A

关 键 词：白藜芦醇 AKT/FoxO3a通路 大鼠 肾间质纤维化 P-AKT p-FoxO3a 

分 类 号：R965[医药卫生—药理学]