ObjectiveTo observe the effects of Zhengan Xifengtang on the blood pressure, bile acid spectrum in plasma, and the expression of farnesoid X receptor (FXR) and fibroblast growth factor 21 (FGF21) in spontaneously hypertensive rats (SHR).MethodsSixty 9-week-old males of SHR were randomized into SHR, benazepril (1.0 mg·kg-1·d-1), high-, medium-, and low-dose (34.5, 17.25, 8.625 g·kg-1·d-1) Zhengan Xifengtang, and agonist (10 mg·kg-1·d-1) groups, and 10 male Wistar-Kyoto (WKY) rats of 9 weeks old were selected as the WKY group. The WKY and SHR groups were administrated with an equal volume of distilled water for 8 consecutive weeks. The liver and plasma samples were collected from the rats. The blood pressure of rats in each group was measured by a tail-cuff method with an animal non-invasive sphygmomanometer. The bile acid spectrum in the plasma of rats in each group was determined by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The expression of FGF21 in the plasma was measured by enzyme-linked immunosorbent assay. The mRNA and protein levels of FXR and FGF21 in the liver tissue were determined by real-time PCR and Western blot, respectively.ResultsZhengan Xifengtang reduced the systolic and diastolic blood pressure of SHR. Compared with the WKY group, the SHR group presented declined levels of ursodeoxycholic acid, hyodeoxycholic acid, deoxycholic acid, lithocholic acid, glycochenodeoxycholic acid, glycoursodeoxycholic acid, and glycohyodeoxycholic acid in the plasma (P<0.05, P<0.01), reduced expression of FGF21 in the plasma (P<0.01), and down-regulated mRNA levels of FXR and FGF21 in the liver (P<0.01). Compared with those in the SHR group, the levels of ursodeoxycholic acid, hyodeoxycholic acid, glycocholic acid, glycochenodeoxycholic acid, glycoursodeoxycholic acid, and glycohyodeoxycholic acid became lowered in the high-dose Zhengan Xifengtang group (P<0.05, P<0.01). The level of deoxycholic acid declined in the low- and medium-dose Zhengan Xifengtang groups (P<0.05). The level of glycocholic acid reduced in the low-dose Zhengan Xifengtang group (P<0.05) and the agonist group (P<0.05). The expression of FGF21 in the plasma and the mRNA levels of FXR and FGF21 in the liver increased in the high-, medium-, and low-dose Zhengan Xifengtang groups and the agonist group (P<0.05, P<0.01). The protein level of FXR in the liver of the medium-dose group and the agonist group was up-regulated (P<0.05, P<0.01). The expression of FGF21 in the liver of the high-dose group increased (P<0.01).ConclusionZhengan Xifengtang may exert the antihypertensive effect by regulating the bile acid spectrum in the plasma and up-regulating the expression of FXR-FGF21 in the liver of SHR.
关键词
Zhengan Xifengtang;hypertension;bile acid spectrum in the plasma;farnesoid X receptor (FXR);fibroblast growth factor 21 (FGF21)