α-硫辛酸对大鼠腹膜纤维化的作用及机制  

Effect of α-lipoic acid on peritoneal fibrosis of rats and its mechanism

作　　者：都元洪 甘平 DU Yuanhong;GAN Ping(School of Clinical Medicine,Guizhou Medical University,Guiyang 550004,Guizhou,China)

机构地区：[1]贵州医科大学临床医学院,贵州贵阳550004

出　　处：《贵州医科大学学报》2023年第4期389-395,共7页Journal of Guizhou Medical University

基　　金：贵州省科技计划项目(黔科合LH字[2017]7199号)。

摘　　要：目的 观察α-硫辛酸(α-LA)对高糖腹膜透析液诱导大鼠腹膜纤维化(PF)的作用及机制。方法 30只SD大鼠随机均分为空白对照组、模型组、α-LA腹腔注射高剂量组(400μmol/L)、α-LA腹腔注射中剂量组(300μmol/L)、α-LA腹腔注射低剂量组(200μmol/L)、α-LA灌胃组(300μmol/L),空白对照组大鼠腹腔注射生理盐水、后5组大鼠腹腔注射高糖腹膜透析液制作PF模型、后4组大鼠同时按分组设计给予相应药物,连续4周。取各组大鼠腹膜组织,苏木素伊红(HE)、Masson’s染色观察腹膜组织学形态及纤维化,免疫组化染色检测α-平滑机动蛋白(α-SMA)及Ⅰ型胶原蛋白(CollagenⅠ)表达,蛋白质印迹法(Western blot)检测转化生长因子β1(TGF-β1)、磷酸化Smad2(p-Smad2)及p-Smad3蛋白表达。结果 处理前各组大鼠体质量组间差异均无统计学意义(P> 0.05),处理后α-LA高剂量腹腔注射组较对照组、模型组和α-LA灌胃组体质量低(P <0.05);纤维化表达面积百分比、腹膜组织α-SMA、CollagenⅠ表达、腹膜组织TGF-β1、p-Smad2及p-Smad3蛋白表达结果显示:模型组大鼠各项指标高于空白对照组(P <0.05);α-LA腹腔注射高剂量组各项指标均低于模型组(P <0.05)、亦低于α-LA灌胃组(P <0.05)。结论 高剂量α-LA能减轻高糖腹膜透析液诱导的大鼠PF,其机制可能与抑制TGF-β1/Smads信号通路激活有关。Objective To observe the effect and mechanism of alpha-lipoic acid(α-LA)on peritoneal fibrosis(PF)induced by high glucose peritoneal dialysis solution(PDS)in rats.Methods Thirty SD rats were randomly divided into the control group,model group,α-LA intraperitoneal injection high-dose group(400μmol/L),α-LA intraperitoneal injection medium-dose group(300μmol/L),α-LA intraperitoneal injection low-dose group(200μmol/L),andα-LA gavage group(300μmol/L).Rats in the control group were injected intraperitoneally with saline,the latter 5 groups were injected intraperitoneally with high-sugar PDS to make PF model,and rats of the latter 4 groups were given the corresponding drugs simultaneously according to the group design for 4 weeks.Peritoneal tissues of each group were taken,and the morphology and fibrosis of the tissues were observed by hematoxylin eosin(HE)and Masson's staining,immunohistochemical staining was performed to detect the expression ofα-smooth motor protein(α-SMA)and collagen typeⅠ(CollagenⅠ),and the expression of transforming growth factorβ1(TGF-β1),phosphorylated Smad2 protein(p-Smad2),and phosphorylated Smad3 protein(p-Smad3)in peritoneal tissues was detected by Western blot.Results The differences in body mass index among the groups before treatment were not statistically significant(P>0.05),and theα-LA high-dose intraperitoneal injection group had lower body mass than the control group,the model group andα-LA gavage group after treatment(P<0.05).The percentage of fibrosis expression area,the expression ofα-SMA and CollagenⅠin peritoneal tissues,and the protein expression of TGF-β1,p-Smad2 and p-Smad3 in peritoneal tissues showed that the indexes increased significantly in the model group compared with the control group(P<0.05);The indexes ofα-LA intraperitoneal injection high dose group were lower than those of the model group(P<0.05)andα-LA gavage group(P<0.05).Conclusion High-doseα-LA can lessen PF of rats induced by high-glucose peritoneal dialysis fluid,and the mechanism ma

关 键 词：腹膜纤维化 腹膜透析液 Α-硫辛酸 腹腔注射 作用机制 

分 类 号：R572.2[医药卫生—消化系统]