摘要
目的基于糖原合酶激酶3β/β连环蛋白(GSK-3β/β-catenin)信号通路探究水蛭素对腹膜纤维化大鼠的干预作用。方法选取6~8周龄SD大鼠60只,随机取10只作为正常组,其余50只建立腹膜纤维化模型。将40只建模成功大鼠随机分为模型组、水蛭素低剂量组、水蛭素高剂量组、氯沙坦钾组,每组10只。正常组和模型组大鼠给予生理盐水灌胃,水蛭素低剂量组给予40 mg/kg水蛭素灌胃,水蛭素高剂量组给予80 mg/kg水蛭素灌胃,氯沙坦钾组给予25 mg/kg氯沙坦钾灌胃,均连续灌胃4周。检测各组大鼠超滤量、葡萄糖转运量;取腹膜组织,测量腹膜厚度,进行HE染色病理观察;取血检测氧化应激指标晚期糖基化终末产物(AGEs)、丙二醛(MDA)、谷胱甘肽(GSH)、总超氧化物歧化酶(T-SOD)水平;RT-PCR法和Western blot法分别检测腹膜组织中GSK-3β、β-catenin mRNA和蛋白表达情况。结果与正常组比较,模型组超滤量及血清GSH、T-SOD水平均明显降低(P均<0.05),葡萄糖转运量、腹膜厚度、血清AGEs和MDA水平及腹膜组织中GSK-3β、β-catenin mRNA和蛋白相对表达量均明显升高(P均<0.05);与模型组比较,水蛭素低、高剂量组和氯沙坦钾组超滤量及血清GSH、T-SOD水平均明显升高(P均<0.05),葡萄糖转运量、腹膜厚度、血清AGEs和MDA水平及腹膜组织中GSK-3β、β-catenin mRNA和蛋白相对表达量均明显降低(P均<0.05);与水蛭素低剂量组比较,水蛭素高剂量组和氯沙坦钾组超滤量及血清GSH、T-SOD水平均更高(P均<0.05),葡萄糖转运量、腹膜厚度、血清AGEs和MDA水平及腹膜组织中GSK-3β、β-catenin mRNA和蛋白相对表达量均更低(P均<0.05);且水蛭素高剂量组超滤量及血清GSH、T-SOD水平均明显高于氯沙坦钾组(P均<0.05),葡萄糖转运量、腹膜厚度、血清AGEs和MDA水平及腹膜组织中GSK-3β、β-catenin mRNA和蛋白相对表达量水平均明显低于氯沙坦钾组(P均<0.05)。结论水蛭素可改善
Objective It is to investigate the interventional effect of hirudin on peritoneal fibrosis in rats via the signaling pathway of glycogen synthase kinase 3β/β-catenin(GSK-3β/β-catenin).Methods Sixty SD rats aged 6-8 weeks were selected,in which 10 rats were randomly taken as the normal group,and the remaining 50 rats were modeled as peritoneal fibrosis.The 40 successfully modeled rats were randomly divided into model group,hirudin low-dose group,hirudin high-dose group,and chlorosartan potassium group,with 10 rats in each group.The rats in the normal group and model group were given normal saline by gavage,the hirudin low-dose group was given 40 mg/kg of hirudin by gavage,the hirudin high-dose group was given 80 mg/kg of hirudin by gavage,and the potassium chlorthalidomide group was given 25 mg/kg of potassium chlorthalidomide by gavage,all continuously gavaged for 4 weeks.The ultrafiltration volume and glucose transport volume of rats in each group were detected;the peritoneal tissues of the rats were taken to detect peritoneal thickness and observe pathological changes by HE staining;the blood of the rats was taken to detect the levels of oxidative stress indicators such as advanced glycosylation end products(AGEs),malondialdehyde(MDA),glutathione(GSH),and total superoxide dismutase(T-SOD);the expressions of GSK-3β,β-catenin mRNA and protein in peritoneal tissues were detected by RT-PCR and Western blot.Results Compared with the normal group,the ultrafiltration volume and the levels of serum GSH and T-SOD were significantly lower(all P<0.05),while the glucose transport,peritoneal thickness,the levels of serum AGEs and MDA,and the relative expressions of GSK-3β,β-catenin mRNA and proteins in the peritoneal tissues were all significantly higher in the model group(all P<0.05).Compared with the model group,the ultrafiltration volume and the levels of serum GSH and T-SOD were significantly higher(all P<0.05),while the glucose transport,peritoneal thickness,the levels of serum AGEs and MDA,and the relative exp
作者
杨薇
平高华
姚吉太
张峥
宋美卿
高峰
YANG Wei;PING Gaohua;YAO Jitai;ZHANG Zheng;SONG Meiqing;GAO Feng(Shanxi Academy of Traditional Chinese Medicine,Taiyuan 030012,Shanxi,China)
出处
《现代中西医结合杂志》
CAS
2023年第16期2203-2208,共6页
Modern Journal of Integrated Traditional Chinese and Western Medicine
基金
山西省自然科学基金面上项目(201801D121297,201801D221386)。
关键词
腹膜纤维化
水蛭素
腹膜功能
氧化应激
peritoneal fibrosis
hirudin
peritoneal function
oxidative stress
