摘要
目的:观察加味肾气丸对糖尿病肾病小鼠肾功能及纤维化的影响,并基于糖原合成酶激酶-3β(GSK-3β)/环磷腺苷效应原件(CREB)信号通路探讨其可能的作用机制。方法:雄性db/db小鼠50只,db/m小鼠10只。50只db/db小鼠按体质量随机分为模型组、厄贝沙坦组、加味肾气丸低、中、高剂量组。db/m小鼠10只为正常组。加味肾气丸低、中、高剂量组中药颗粒剂混悬液灌胃,厄贝沙坦组给予厄贝沙坦混悬液灌胃,正常组及模型组予等体积蒸馏水灌胃,连续干预12周。分别记录治疗前后小鼠的血糖和尿白蛋白肌酐比(UACR)及小鼠肾脏中GSK-3β、CREB、转化生长因子-β_(1)(TGF-β_(1))、钙黏蛋白E(E-cadherin)、波形蛋白(Vimentin)、纤维粘连蛋白(FN)、纤溶酶原激活物抑制剂-1(PAI-1)、Ⅳ型胶原蛋白(ColⅣ)蛋白的表达水平,并观测小鼠肾脏的病理损伤程度。结果:与正常组比较,模型组小鼠血糖、UACR水平及肾脏中GSK-3β、TGF-β_(1)、E-cadherin、Vimentin、FN、PAI-1、ColⅣ蛋白的表达水平明显升高(P<0.05),CREB蛋白表达水平明显下降(P<0.05),小鼠肾脏病理损伤严重;与模型组比较,肾气丸低、中、高剂量组和厄贝沙坦组小鼠血糖、UACR水平及肾脏中GSK-3β、TGF-β_(1)、E-cadherin、Vimentin、FN、PAI-1、ColⅣ蛋白的表达水平均有不同程度下降(P<0.05),CREB蛋白表达水平升高(P<0.05),小鼠肾脏病理损伤有不同程度的减轻。结论:肾气丸可有效降低血糖、改善肾功能和纤维化,其作用机制与其抑制GSK-3β/CREB信号通路有关。
Objective:To observe the effects of modified Shenqiwan on renal function and fibrosis in diabetic nephropathy mice and explore the underlying mechanism based on the glycogen synthase kinase-3β(GSK-3β)/cyclic adenosine monophosphate(cAMP)response element-binding protein(CREB)signaling pathway.Method:Fifty male db/db mice and 10 db/m mice were used in this study.The fifty db/db mice were randomly divided into model group,irbesartan group,and low-,medium-,and high-dose modified Shenqiwan groups.The 10 db/m mice were assigned to the normal group.The mice in the low-,medium-,and high-dose modified Shenqiwan groups were administered with modified Shenqiwan in the dosage form of suspension of Chinese medicinal granules by gavage,those in the irbesartan group were given irbesartan suspension by gavage,and those in the normal and model groups were given distilled water of equal volume by gavage.The intervention lasted for 12 weeks.The blood glucose levels,urine albumin-to-creatinine ratio(UACR),and the protein expression levels of GSK-3β,CREB,transforming growth factor-β_(1)(TGF-β_(1)),E-cadherin,Vimentin,fibronectin(FN),plasminogen activator inhibitor-1(PAI-1),and Collagen typeⅣ(CollⅣ)in the mouse kidneys were recorded before and after treatment.The extent of renal pathological damage was also observed.Result:Compared with the normal group,the model group showed significant increases in blood glucose levels,UACR levels,and the protein expression levels of GSK-3β,TGF-β_(1),E-cadherin,Vimentin,FN,PAI-1,and CollⅣin the kidneys(P<0.05),decreased protein expression level of CREB(P<0.05),and severe renal pathological damage.Compared with the model group,the low-,medium-,and high-dose modified Shenqiwan groups and the irbesartan group showed varying degrees of decreases in blood glucose levels,UACR levels,and the protein expression levels of GSK-3β,TGF-β_(1),E-cadherin,Vimentin,FN,PAI-1,and CollⅣin the kidneys(P<0.05),increased expression level of CREB protein(P<0.05),and improved renal pathological damage.Conc
作者
张佳华
宁洪悦
安丽萍
纪品川
常柏
齐好雯
郭建恩
ZHANG Jiahua;NING Hongyue;AN Liping;JI Pinchuan;CHANG Bai;QI Haowen;GUO Jianen(Chengde Medical University,Chengde 067000,China;Chengde Hospital of Traditional Chinese Medicine,Chengde 067000,China;Zhu Xianyi Memorial Hospital of Tianjin Medical University,Tianjin 300134,China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2023年第16期162-169,共8页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家自然科学基金项目(81973614)
河北省自然科学基金联合基金项目(H2022406069)。
