Effects of Zhengan Xifeng decoction on bile acid-TGR5/Rho/ROCK/AgRP signaling pathway in spontaneously hypertensive rats
Objective To observe the effects of Zhengan Xifeng decoction on bile acid-Takeda G protein-coupled receptor 5(TGR5)/Ras homolog(Rho)/Rho-associated coiled-coil containing protein kinase(ROCK)/agouti-related protein(AgRP)signaling pathway in spontaneously hypertensive rats(SHR).Methods Seventy SHR were randomly divided into the model group,control group(gavage administration of 0.5 mg·kg-1·d-1 amlodipine besylate tablets),experimental-L,-M,-H group(gavage administration of 8.630 x 103,1.725 × 104,3.450 × 104 mg·kg-1·d-1 Zhengan Xifeng decoction).Fifteen Wistar-Kyoto rats served as the normal group.The model and normal groups were given the same amount of distilled water.Six groups were treated for 8 weeks with once a day.The bile acid profiles of jejunum contents and colon contents were detected by ultra-high-performance liquid chromatography-tandem mass spectrometry,and the expression levels of TGR5,Rho,ROCK and AgRP proteins in the hypothalamus were detected by Western blot.Results Compared with the normal,mode,control groups and experimental-L,-M,-H groups,the bile acid spectrum of jejunum contents was significantly changed,and 6 different bile acids were found,namely glycoursodeoxycholic acid,glycohyodeoxycholic acid,hyodeoxycholic acid,ursodeoxycholic acid,taurochenodeoxycholic acid and chenodeoxycholic acid.The bile acid spectrum of colon contents was significantly changed,and 4 different bile acids were found,namely deoxycholic acid,ursodeoxycholic acid,lithocholic acid and hyodeoxycholic acid.The relative expression levels of TGR5 protein in normal,model,control and experimental-M groups were 1.01±0.22,0.75±0.23,0.96±0.16 and 1.02±0.21;the relative expression levels of Rho protein were 0.81±0.14,0.58±0.19,0.83±0.27 and 0.94±0.24;the relative expression levels of ROCK protein were 0.99±0.27,0.65±0.13,1.07±0.22 and 1.06±0.24;the relative expression levels of AgRP protein were 0.98±0.33,1.46±0.45,0.83±0.25 and 0.95±0.33,respectively.Compared with the model group,the above indexes in the experimental-M group and the normal group showed significant differences(all P＜0.05).Conclusion Zhengan Xifeng decoction may suppress AgRP expression via bile acid-TGR5/Rho/ROCK/AgRP signaling pathway,to achieve the purpose of reducing blood pressure.
Zhengan Xifeng decoctionhypertensionbile acidTakeda G protein-coupled receptor 5agouti-related protein
万方数据
维普
