文献类型：期刊文献

中文题名：基于Wnt/β-catenin信号通路探讨红芪多糖对糖尿病肾病db/db小鼠作用机制

英文题名：Mechanism of Hedysarum Polysaccharide in Diabetic Nephropathy in db/db Mice Based on Wnt/β-catenin Signal Pathway

作者：陈彦旭[1];金彩云[1];金智生[1];姜晓雪[1];张博玲[1];伏瑶琴[1];何流[2]

第一作者：陈彦旭

机构：[1]甘肃中医药大学,兰州730000;[2]贵州中医药大学第二附属医院,贵阳550000

第一机构：甘肃中医药大学

年份：2022

卷号：28

期号：21

起止页码：74

中文期刊名：中国实验方剂学杂志

外文期刊名：Chinese Journal of Experimental Traditional Medical Formulae

收录：CSTPCD;;北大核心:【北大核心2020】；CSCD:【CSCD2021_2022】；

基金：国家自然科学基金项目(81660777);甘肃中医药大学科学研究与创新基金项目(30140311)。

语种：中文

中文关键词：红芪多糖;糖尿病肾病;肾损伤;Wnt1;β-连环蛋白(β-catenin);糖原合成激酶-3β(GSK-3β);磷酸化糖原合成激酶-3(βp-GSK-3β)

外文关键词：Hedysarum polysaccharides;diabetic nephropathy;renal injury;Wnt1;β-catenin;glycogen synthesis kinase-3β(GSK-3β);phosphorylated GSK-3β(p-GSK-3β)

摘要：目的:观察红芪多糖(HPS)对糖尿病肾病db/db小鼠Wnt/β-连环蛋白(β-catenin)信号通路的影响。方法:将50只db/db小鼠按体质量随机分为模型组、厄贝沙坦组、HPS高、中、低剂量组,每组10只;另取10只C57BL/6小鼠作为正常组。正常组和模型组给予5 m L·kg^(-1)·d^(-1)蒸馏水,厄贝沙坦组给予22.75 mg·kg^(-1)·d^(-1)厄贝沙坦溶液,HPS高、中、低剂量组分别给予200、100、50 mg·kg^(-1)·d^(-1)HPS溶液。6组小鼠每日灌胃1次,连续给药12周。检测各组小鼠一般状态、血糖(GLU)、24 h尿蛋白(UTP)、血肌酐(SCr)、尿素氮(BUN),苏木素-伊红(HE)染色观察肾脏组织病理变化,蛋白免疫印迹法(Western blot)、实时荧光定量聚合酶链式反应(Real-time PCR)检测肾脏中Wnt1、β-catenin、糖原合成激酶-3β(GSK-3β)及磷酸化糖原合成激酶-3β(p-GSK-3β)的蛋白及m RNA的表达水平。结果:治疗12周后,与正常组比较,模型组小鼠一般状态较差且肾脏组织病理超微结构病变显著,其GLU、24 h UTP、SCr、BUN水平均升高(P<0.01);与模型组比较,HPS高、中剂量组小鼠一般状态及肾脏组织病理超微结构均得到一定程度改善,其GLU、24 h UTP、SCr、BUN水平均降低(P<0.05,P<0.01);与正常组比较,模型组Wnt1、β-catenin、GSK-3β及p-GSK-3βm RNA及蛋白表达水平均升高(P<0.01);与模型组比较,HPS高、中剂量组Wnt1、β-catenin、GSK-3β及p-GSK-3βm RNA及蛋白表达水平均明显降低(P<0.05,P<0.01)。结论:HPS可在一定程度上减轻糖尿病肾病的肾损伤,其机制可能与抑制Wnt/β-catenin信号通路激活有关。
Objective:To observe the effect of Hedysarum polysaccharides(HPS)on the Wnt/β-catenin signal pathway in db/db mice with diabetic nephropathy.Method:Fifty db/db mice were randomly divided into model group,irbesartan group,and high,middle,and low-dose HPS experimental groups according to their body mass,with 10 mice in each group,and another 10 C57BL/6 mice were selected as a normal group.The normal group and the model group were given 5 m L·kg^(-1)·d^(-1)distilled water,the irbesartan group was given 22.75 mg·kg^(-1)·d^(-1)irbesartan suspension,and the high,middle,and low-dose HPS experimental groups were given 200,100,and 50 mg·kg^(-1)·d^(-1)HPS suspensions,respectively.The mice in the 6groups were given intragastric administration once a day for 12 weeks.The general state,blood glucose(GLU),24 h urine protein(UTP),blood creatinine(SCr),and urea nitrogen(BUN)of mice in each group were determined.The pathological changes in the kidney tissue were observed by hematoxylin-eosin staining(HE).The protein and m RNA expression levels of Wnt1,β-catenin,glycogen synthesis kinase-3β(GSK-3β),and phosphorylated GSK-3β(p-GSK-3β)in the kidney were detected by Western blot and real-time fluorescence quantitative polymerase chain reaction(Real-time PCR).Result:After treatment for 12 weeks,as compared with the normal group,the general state of mice in the model group was worse and the pathological ultrastructural lesions of kidney tissues were obvious.The levels of GLU,24 h UTP,SCr,and BUN in the model group increased(P<0.01).As compared with the model group,the general state and renal pathological ultrastructure of mice in the high and middle-dose HPS groups were improved to some extent,and the levels of SCr,BUN,and 24 h UTP in the high and middle-dose HPS groups decreased(P<0.05,P<0.01).As compared with the normal group,the expression levels of Wnt1,β-catenin,GSK-3β,and p-GSK-3βprotein and m RNA in the model group were higher(P<0.01),while the expression levels of Wnt1,β-catenin,GSK-3β,and p-GSK-3βprotein and m RNA in the high and middle-dose HPS groups were lower than those in the model group(P<0.05,P<0.01).Conclusion:HPS can alleviate the renal injury of diabetic nephropathy to some extent,and its mechanism may be related to the inhibition of the activation of the Wnt/β-catenin signal pathway.