加味大黄附子汤调节Wnt/β-catenin信号通路保护慢性肾脏病小鼠认知功能的机制  

Protection mechanism of modified Dahuang Fuzi Decoction on cognitive function in mice with chronic kidney disease by regulating Wnt/β-catenin signaling pathways

作　　者：孔文文 巴元明[2] KONG Wen-wen;BA Yuan-ming(Hubei University of Chinese Medicine,Wuhan 430070;Department of Nephrology,Hubei Provincial Hospital of Traditional Chinese Medicine,Wuhan 430060,Hubei,China)

机构地区：[1]湖北中医药大学,湖北武汉430070 [2]湖北省中医院肾病科,湖北武汉430060

出　　处：《川北医学院学报》2023年第9期1161-1164,1168,共5页Journal of North Sichuan Medical College

基　　金：湖北省科技重大专项项目(2021ACA004-03)。

摘　　要：目的:探究加味大黄附子汤保护慢性肾脏病小鼠的认知功能及其机制。方法:采用0.2%腺嘌呤饲料喂养5周建立慢性肾脏病模型,成功建模后将小鼠随机分为模型组,加味大黄附子汤低、中、高剂量组(低、中、高剂量组),加味大黄附子汤高剂量+Wnt/β-环形蛋白(β-catenin)信号通路抑制剂(IWR-I)组(高剂量+IWR-I组),每组各10只,另取10只正常C57BL/6小鼠作对照组。低、中、高剂量组分别灌胃8、16、24 g/kg加味大黄附子汤,高剂量+IWR-I组灌胃24 g/kg加味大黄附子汤+腹腔注射5 mg/kg IWR-I。采用Morris水迷宫实验评价小鼠认知功能,眼眶取血检测血清肌酐、尿素氮、乙酰胆碱酯酶(AChE)和胆碱乙酰转移酶(ChAT)水平,HE染色观察肾脏及脑组织病理学变化,Western blot法检测脑组织Wnt3a、β-catenin蛋白表达。结果:与模型组比较,中、高剂量组第3~5天逃避潜伏期、血清肌酐、尿素氮、AChE水平均降低,穿越平台次数、ChAT、脑组织中Wnt3a、β-catenin蛋白表达水平均升高(P<0.05);与高剂量组比较,高剂量+IWR-I组第2~5天逃避潜伏期、肌酐、尿素氮、AChE水平均升高,穿越平台次数、ChAT、脑组织中Wnt3a、β-catenin蛋白表达水平均降低(P<0.05)。结论:加味大黄附子汤可改善慢性肾脏病小鼠认知功能,其作用可能与激活Wnt/β-catenin信号通路有关。Objective:To explore the effect and mechanism of modified Dahuang Fuzi Decoction on protecting cognitive function in mice with chronic kidney disease(CKD).Methods:The mice were fed with 0.2%adenine diet for 5 weeks to construct CKD models.After successful modeling,mice were randomly divided into model group,low-dose,medium-dose and high-dose modified Dahuang Fuzi Decoction groups(low-dose,medium-dose and high-dose groups),and high-dose modified Dahuang Fuzi Decoction+Wnt/β-catenin signaling pathway inhibitor(IWR-I)group(high-dose+IWR-I group),10 cases in each group.Another 10 normal C57BL/6 mice were selected as control group(no treatment).low-dose,medium-dose and high-dose groups were given intragastric administration of modified Dahuang Fuzi Decoction(8,16,24 g/kg),and high-dose+IWR-I group was given intragastric administration of modified Dahuang Fuzi Decoction(24 g/kg)and intraperitoneal injection of IWR-I(5 mg/kg).The cognitive function of mice was evaluated by Morris water maze test.The orbital blood was collected to detect levels of serum creatinine,blood urea nitrogen,acetylcholin esterase(AChE)and choline acetyltransferase(ChAT).The pathological changes of kidney and brain tissues were observed by HE staining.The expressions of Wnt3a andβ-catenin in brain tissues were detected by Western blot.Results:Compared with model group,escape latency on 3~5 day,serum creatinine,blood urea nitrogen and AChE were decreased,while times of crossing the platform,ChAT and expressions of Wnt3a andβ-catenin in brain tissues were increased in medium-dose and high-dose groups(P<0.05).Compared with high-dose group,escape latency on 3~5 day,serum creatinine,blood urea nitrogen and AChE were increased,while times of crossing the platform,ChAT and expressions of Wnt3a andβ-catenin in brain tissues were decreased in high-dose+IWR-I group(P<0.05).Conclusion:Modified Dahuang Fuzi Decoction can improve cognitive function of CKD mice,which may be related to activating Wnt/β-catenin signaling pathways.

关 键 词：慢性肾脏病 加味大黄附子汤 认知功能 WNT/Β-CATENIN信号通路 

分 类 号：R692[医药卫生—泌尿科学]