摘要
目的探讨桃核承气汤对肾纤维化大鼠的保护作用机制。方法按照体重将大鼠随机分为6组:正常组、模型组、对照组和低、中、高3个剂量实验组,每组10只。除正常组外,其余各组大鼠按250 mg·kg^(-1)灌胃腺嘌呤溶液建立肾纤维化模型。低、中、高3个剂量实验组大鼠分别按1.89,3.78,7.56 g·kg^(-1)灌胃桃核承气汤水煎液;对照组大鼠按9 mg·kg^(-1)灌胃氯沙坦溶液;正常组和模型组大鼠灌胃等量生理盐水,1次/天,连续30 d。用酶联免疫吸附法检测血清肌酸酐(Cr)和尿素氮(BUN)含量;用免疫组织化学法检测肾组织分泌型糖蛋白5a(Wnt5a)和β-连环蛋白(β-catenin)表达水平;用蛋白质印迹法检测肾组织Notch信号受体1(Notch1)和Notch信号配体1(Jagged1)表达水平(灰度值)。结果正常组、模型组、对照组和低、中、高3个剂量实验组Cr含量分别为(0.11±0.01),(0.72±0.09),(0.16±0.03),(0.25±0.02),(0.19±0.02)和(0.17±0.01)mmol·L^(-1);这6组的BUN含量分别为(5.19±0.15),(8.93±0.59),(5.61±0.30),(7.35±0.20),(6.53±0.33)和(4.98±0.38)mmol·L^(-1);这6组的Wnt5a蛋白相对表达量分别为14.80±1.81,21.89±0.63,13.96±0.63,19.30±1.28,16.99±0.78和17.03±0.73;这6组的β-catenin蛋白相对表达量分别为19.16±0.93,22.19±0.88,17.45±0.53,20.06±1.09,18.60±0.52和15.37±0.79;这6组的Notch1蛋白相对表达量分别为82.82±2.46,88.53±1.26,77.06±3.13,68.68±3.83,59.12±2.91和63.20±0.84;这6组的Jagged1蛋白相对表达量分别为78.20±2.49,95.35±1.05,84.44±3.92,85.61±3.88,73.90±3.37和61.91±1.07。上述指标:模型组与正常组比较,差异均有统计学意义(均P<0.01);对照组和低、中、高3个剂量实验组与模型组比较,差异均有统计学意义(均P<0.01)。结论桃核承气汤可以显著抑制肾纤维化大鼠肾组织中Wnt/β-catenin和Notch-Hes1信号通路,从而发挥对肾纤维化大鼠的保护作用。
Objective To study the protective effect and mechanism of Taohe Chengqi Decoction(TCD)on renal fibrosis(RF)model in rats.Methods The rats were randomly divided into six groups according to weight:normal group,model group,control groupand experimental-L,-M,-H groups,10 rats in each.Dose of the 250 mg·kg^(-1)adenine induced RF in the rats of model group,control group and experimentalL,-M,-H groups.Rats were administered with normal saline respectively in normal and model group.Rats in the control group were administered with 9 mg·kg^(-1)losartan by gastrogavage.Rats in the experimental-L,-M,-H groups were administered with TCD(1.89,3.78,7.56g·kg^(-1))by gastrogavage,once daily for 30 consecutive days.The contents of creatinine(Cr)and blood urea nitrogen(BUN)were detected by enzyme-linked immunosorbent assay.The expression levels of Wingless/Integrated(Wnt5a)andβ-catenin in renal tissue were detected by immunohistochemistry(IHC).The expression levels of Notch1 and Jagged1 in renal tissue were detected by western blotting(gray value).Results The contents of Cr in normal group,model group,control group and experimental-L,-M,-H groups were(0.11±0.01),(0.72±0.09),(0.16±0.03),(0.25±0.02),(0.19±0.02),(0.17±0.01)mmol·L^(-1),respectively;the contents of BUN in the six groups were(5.19±0.15),(8.93±0.59),(5.61±0.30),(7.35±0.20),(6.53±0.33),(4.98±0.38)mmol·L^(-1),respectively;the relative expression levels of Wnt5a in the six groups were 14.80±1.81,21.89±0.63,13.96±0.63,19.30±1.28,16.99±0.78 and 17.03±0.73,respectively;the relative expression levels ofβ-catenin in the six groups were 19.16±0.93,22.19±0.88,17.45±0.53,20.06±1.09,18.60±0.52 and 15.37±0.79,respectively;the relative expression levels of Notch1 in the six groups were 82.82±2.46,88.53±1.26,77.06±3.13,68.68±3.83,59.12±2.91 and 63.20±0.84,respectively;the relative expression levels of Jagged1 in the six groups were 78.20±2.49,95.35±1.05,84.44±3.92,85.61±3.88,73.90±3.37 and 61.91±1.07,respectively.Comparison between model group and normal group,the difference of the factors were significant(all P<0.01);comparison between control group,three dose experimental groups and model group,the difference of the factors were significant(all P<0.01).Conclusion TCD has a protective effect on RF rats,and its mechanism may be related to the inhibition of Wnt/β-catenin and Notch-Hes1 signal pathway.
作者
张明昊
高一盈
赵盈盈
赵丹萍
徐一凡
于凌爽
姚文佳
李婉辰
王凯
ZHANG Ming-hao;GAO Yi-ying;ZHAO Ying-ying;ZHAO Dan-ping;XU Yi-fan;YU Ling-shuang;YAO Wen-jia;LI Wan-chen;WANG Kai(School of Basic Medicine,Henan University of Chinese Medicine,Zhengzhou 450046,Henan Province,China;School of Pharmacy,Henan University of Chinese Medicine,Zhengzhou 450046,Henan Province,China;School of Rehabilitation Medicine,Henan University of Chinese Medicine,Zhengzhou 450046,Henan Province,China;School of Second Clinical Medicine,Henan University of Chinese Medicine,Zhengzhou 450046,Henan Province,China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2021年第17期2324-2327,2334,共5页
The Chinese Journal of Clinical Pharmacology
基金
国家自然科学基金面上基金资助项目(31071923)
河南中医药大学科研苗圃工程基金资助项目(MP2020-01)
河南中医药大学药学院大学生创新学习基金资助项目(YXCX[2019]2)。
