摘要
目的观察α1肾上腺素受体(α1AR)阻滞剂能否降低和拮抗α1AR激活导致的大鼠门静脉高压,为临床治疗门静脉高压提供新思路。方法α1AR激动剂选用去氧肾上腺素,α1AR阻滞剂选用阿呋唑嗪,采用门静脉穿刺注射给药并测量门静脉压力。将32只雄性Sprague-Dawley大鼠按随机数字表法分为4组。所有大鼠均在给药前测量基础门静脉压力;对照组大鼠按体重经门静脉注射0.9%氯化钠溶液(1 L/g),门静脉高压模型组大鼠经门静脉注射去氧肾上腺素(1.5μg/g),以上两组在给药5和10 min后分别测量门静脉压力;阿呋唑嗪治疗组大鼠经门静脉予去氧肾上腺素(1.5μg/g)5 min后测压,再予阿呋唑嗪(0.9μg/g),在5 min后再次测压;阿呋唑嗪预防组大鼠经门静脉给予阿呋唑嗪(0.9μg/g)预处理1 min后测压,再予去氧肾上腺素(1.5μg/g),在1、5和10 min后测压。采用单因素方差分析、Dunnett-t检验进行统计学分析。结果对照组、门静脉高压模型组、阿呋唑嗪治疗组和阿呋唑嗪预防组分别有4、6、8、5只大鼠门静脉穿刺成功。门静脉高压模型组大鼠给药5和10 min后门静脉压力分别为(18.045±7.636)、(15.515±5.440)mmHg(1 mmHg=0.133 kPa),均高于给药前[(8.452±2.830)mmHg],差异均有统计学意义(t=2.89、2.82,均P<0.05)。阿呋唑嗪治疗组大鼠在注射阿呋唑嗪5 min后,门静脉压力为(10.088±3.743)mmHg,低于本组注射去氧肾上腺素5 min后[(16.146±4.324)mmHg]和门静脉高压模型组注射去氧肾上腺素10 min后,差异均有统计学意义(t=3.00、2.22,均P<0.05)。阿呋唑嗪预防组大鼠给药前,注射阿呋唑嗪后,注射去氧肾上腺素后各时间点的门静脉压力比较差异均无统计学意义(均P>0.05)。结论α1AR是参与门静脉压力调节的重要因素,其阻滞剂能降低和拮抗α1AR激活导致的门静脉高压,对防治肝硬化门静脉高压进展具有重要意义。
Objective To observe whetherα1 adrenergic receptor(α1AR)blocker can reduce and antagonize portal hypertension caused byα1AR activation in rats,and to provide a new approach for the clinical treatment of portal hypertension.Methods Phenylephrine was chosen asα1AR agonist,and alfuzosin was used asα1AR blocker.The route of administration was portal vein injection,and the pressure was measured by trans-portal vein puncture.According to random number table,32 male Sprague-Dawley rats were divided into 4 groups:control group,portal hypertension model group,alfuzosin treatment group and alfuzosin prevention group.The portal venous pressure(PVP)was measured in all rats before administration.The rats in the control group were injected with 0.9%sodium chloride solution(1 L/g),and the rats in portal hypertension model group were injected with phenylephrine(1.5μg/g),and the PVP of the above two groups was measured again at 5 and 10 min after injection.The rats in alfuzosin treatment group were injected with phenylephrine(1.5μg/g),PVP was measured again at 5 min after administration,and then the rats were given alfuzosin(0.9μg/g),PVP was measured again at 5 min after administration.The rats in alfuzosin prevention group were injected with alfuzosin(0.9μg/g),PVP was measured at 1 min after administration,and then the rats were given phenylephrine(1.5μg/g),PVP was measured again at 1,5 and 10 min after phenylephrine injection respectively.One way analysis of variance and Dunnett-t test were used for statistical analysis.Results The portal vein puncture was successfully performed in 4,6,8 and 5 rats in the control group,portal hypertension model group,alfuzosin treatment group and alfuzosin prevention group,respectively.The PVP of rats in portal hypertension model group at 5 and 10 min after phenylephrine injection was(18.045±7.636)and(15.515±5.440)mmHg(1 mmHg=0.133 kPa),respectively,which were both higher than that before administration((8.452±2.830)mmHg),and the differences were statistically significant(t=2.89 and 2.82,both P<0.05).At 5 min after alfuzosin injection,the PVP of rats in the alfuzosin treatment group was(10.088±3.743)mmHg,which was lower than that of rats at 5 min after phenylephrine injection((16.146±4.324)mmHg)and that of portal hypertension model group at 10 min after phenylephrine injection,and the differences were statistically significant(t=3.00 and 2.22,both P<0.05).There were no significant differences in PVP in the alfuzosin prevention group before administration,at 1 min after injection of alfuzosin,and at 1,5 and 10 min after injection of phenylephrine(all P>0.05).Conclusionsα1AR is an important factor involved in the regulation of PVP,and its blockers can reduce and antagonize the portal hypertension caused byα1AR activation,which is of great significance in the prevention and treatment of portal hypertension progression in liver cirrhosis.
作者
李振
王广川
王思宁
赵连晖
张春清
Li Zhen;Wang Guangchuan;Wang Sining;Zhao Lianhui;Zhang Chunqing(Department of Gastroenterology,Shandong Provincial Hospital Affiliated to Shandong First Medical University,Jinan 250021,China)
出处
《中华消化杂志》
CAS
CSCD
北大核心
2022年第5期336-339,共4页
Chinese Journal of Digestion
基金
国家自然科学基金(81970533)。
关键词
Α1肾上腺素受体
门静脉高压
肝硬化
肝纤维化
α1 adrenergic receptor
Portal hypertension
Liver cirrhosis
Liver fibrosis