文献类型：期刊文献

中文题名：镇肝熄风汤对自发性高血压大鼠胆汁酸谱及甾醇12α羟化酶的影响

英文题名：Effects of Zhengan Xifeng decoction on bile acid spectrum of bile and sterol 12αhydroxylase in spontaneously hypertensive rats

作者：凌必时[1];金华[1];祁尚文[1];刘双芳[1];刘志军[2]

第一作者：凌必时

机构：[1]甘肃中医药大学中医临床学院,甘肃兰州730000;[2]甘肃中医药大学附属医院神经内科,甘肃兰州730000

第一机构：甘肃中医药大学中医临床学院

年份：2024

卷号：40

期号：15

起止页码：2212

中文期刊名：中国临床药理学杂志

外文期刊名：The Chinese Journal of Clinical Pharmacology

收录：CSTPCD;;北大核心:【北大核心2023】；CSCD:【CSCD2023_2024】；

基金：国家自然科学基金资助项目(82160886,81860832);甘肃省自然科学基金资助项目(20JR10RA315,22JR5RA579);甘肃省中医药科研基金资助项目(GZK-2019-24)。

语种：中文

中文关键词：镇肝熄风汤;高血压;胆汁酸谱;胆汁;甾醇12α羟化酶

外文关键词：Zhengan Xifeng decoction;hypertension;bile acid spectrum;bile;sterol 12αhydroxylase

摘要：目的观察镇肝熄风汤对自发性高血压大鼠(SHR)胆汁酸谱及甾醇12α羟化酶(CYP8B1)的影响。方法将50只SHR随机分为模型组、对照组(灌胃1.0 mg·kg^(-1)·d^(-1)贝那普利)和低、中、高剂量实验组(灌胃镇肝熄风汤8.63、17.25、34.50 g·kg^(-1)·d^(-1));另取10只同源雄性京都Wistar大鼠作为正常组。模型组和正常组均灌胃给予等量蒸馏水。6组大鼠每天给药1次,连续给药8周。用动物无创血压计以尾套法测量各组大鼠血压,用UPLC-MS/MS法检测各组大鼠胆汁酸谱,用实时荧光定量聚合酶链反应法检测大鼠肝组织中CYP8B1 mRNA的表达情况。结果中、高剂量实验组和对照组、模型组、正常组的第8周收缩压分别为(169.63±12.10)、(170.32±9.64)、(175.95±15.47)、(189.47±7.42)和(146.40±9.45)mmHg,第8周舒张压分别为(135.10±11.99)、(129.73±15.10)、(135.18±17.62)、(149.20±8.83)和(110.53±10.92)mmHg,CYP8B1 mRNA相对表达水平分别为3.36±0.94、5.45±1.46、4.29±0.95、0.89±0.14和1.00±0.00。中、高剂量实验组的上述指标与模型组比较,在统计学上差异均有统计学意义(P<0.01,P<0.05)。低、中、高剂量实验组与模型组比较,胆汁酸谱改变明显,共发现9种差异胆汁酸,分别为猪去氧胆酸、甘氨猪去氧胆酸、甘氨鹅去氧胆酸、甘氨熊去氧胆酸、α-鼠胆酸、熊去氧胆酸、胆酸、β-鼠胆酸、甘氨胆酸。结论镇肝熄风汤可能通过上调肝CYP8B1表达,纠正胆汁酸谱紊乱,从而达到降低血压的目的。
Objective To observe the effects of Zhengan Xifeng decoction on bile acid spectrum of bile and sterol 12α hydroxylase(CYP8B1)in spontaneously hypertensive rats(SHR).Methods Fifty SHR were randomly divided into model group,control group(1.0 mg·kg^(-1)·d^(-1)benazepril by gavage)and experimental-L,-M,-H groups(8.63,17.25 and 34.50 g·kg^(-1)·d^(-1)Zhengan Xifeng decoction by gavage),another 10 homologous male Wistar-Kyoto(WKY)rats were taken as the normal group.The model group and the normal group were given the same amount of distilled water.The rats in the 6 groups were administered once a day for 8 weeks.The animal non-invasive sphygmomanometer was used to measure the blood pressure of rats in each group by tail-cuff method;the bile acid spectrum of rats in each group was detected by UPLC-MS/MS;the expression of CYP8B1 mRNA in rat liver tissue was detected by real-time fluorescence quantitative polymerase chain reaction.Results The systolic blood pressure at the 8thweek of the experimental-M,-H groups,control group,model group,normal group were(169.63±12.10),(170.32±9.64),(175.95±15.47),(189.47±7.42)and(146.40±9.45)mmHg;the diastolic blood pressure at the 8^(th)week were(135.10±11.99),(129.73±15.10),(135.18±17.62),(149.20±8.83)and(110.53±10.92)mmHg;the relative expression levels ofCYP8B1 mRNA were 3.36±0.94,5.45±1.46,4.29±0.95,0.89±0.14 and 1.00±0.00,respectively.Compared with the model group,the above indexes in the experimental-M,-H groups were statistically significant(P<0.01,P<0.05).Compared with the model group,the bile acid spectrum of experimental-L,-M,-H groups bile changed significantly,and a total of 9 different bile acids were found,which were hyodeoxycholic acid,glycohyodeoxycholic acid,glycochenodeoxycholic acid,glycoursodeoxycholic acid,α-muricholic acid,ursodeoxycholic acid,cholic acid,β-muricholic acid andglycocholic acid.Conclusion Zhengan Xifeng decoction may correct bile acid spectrum disorder of bile and reduce blood pressure by up-regulating liver CYP8B1 expression.