甘草甜素对大鼠血压的影响及其机制  

Effects of glycyrrhizin on blood pressure and its mechanisms

作　　者：张永生[1] 吴平生[1] 刘伊丽[1] 王煊[1] 梁欣伟[1] 郭志刚[1] 赖文岩[1] 

机构地区：[1]第一军医大学南方医院心内科

出　　处：《中华内科杂志》1999年第5期302-305,共4页Chinese Journal of Internal Medicine

摘　　要：目的探讨甘草甜素通过抑制１１β羟化固醇脱氢酶２型催化活性导致血压升高及其机制。方法对９只及６只Ｗｉｓｔａｒ大鼠给予外源性甘草甜素５周及３个月后观察血压变化，光镜检查心脏及主动脉的滋养动脉的病理改变，观察肠系膜动脉对去甲肾上腺素加压反应，并通过肠系膜血管网的离体灌注，检测灌注液中皮质醇及醛固酮的含量，通过ＲＴＰＣＲ观察甘草甜素处理大鼠主动脉１１β羟化固醇脱氢酶２型及醛固酮合成酶ｍＲＮＡ表达的变化。结果甘草甜素使大鼠血压升高，心脏及主动脉的滋养动脉出现平滑肌细胞增生和肥大，血管壁增厚及玻璃样变性，肠系膜动脉对去甲肾上腺素的加压反应增高，肠系膜血管网灌注液中皮质醇含量增高及醛固酮含量减低，主动脉１１β羟化固醇脱氢酶２型及醛固酮合成酶ｍＲＮＡ的表达受抑。结论提示甘草甜素通过抑制１１β羟化固醇脱氢酶２型及醛固酮合成酶ｍＲＮＡ的表达，导致局部组织皮质醇水平增高、醛固酮降低，增加血管平滑肌对去甲肾上腺素的反应性引起血压升高。Objective To confirm the action of glycyrrhizin on blood pressure by inhibiting the activity of 11hydroxysteroid dehydrogenase type (11HSD 2) and to test its mechanism. Methods Male Wistar rats and SHRs (weighing 150220 g) were given glycyrrhizin (Sigma) 200 mg/kg /day, orally for 5 weeks and 3 months. The blood pressure was monitored by means of a pressure transducer connected to a polygraph and recorded. Histological pathological chages of the nutrient arteries of the heart and aorta were studied with light microscope. Mesenteric artery perfusion ex vivo and pressor responses to norepinephrine were performed. The perfusate from the mesenteric arteries was collected and used for reverse phase high performance liquid chromatography to measure aldosterone and corticosterone level. RTPCR was used to measure the expression of 11HSD 2 and aldosterone synthase (CYP11B2) mRNA. Results The results showed that the systolic blood pressure was significantly increased in Wistar rats treated with glycyrrhizin compared with those not treated. Hyperplasia of smooth muscle cells and hypertrophy in arterioles were observed under microscope. The pressor responses to norepinephrine in mesenteric arteries treated with glycyrrhizin were significantly increased. The level of aldosterone was decreased but that of corticosterone was increased in perfusate treated with glycyrrhizin. RTPCR showed that glycyrrhizin inhibited the expression of 11HSD2and CYP11B2 mRNA in aorta. Conclusion These results confirm that glycyrrhizin is able to induce hypertension. There is evidence that it inhibits the enzymes of both 11HSD2 and CYP11B2 in vasculature and leads to higher corticosterone and lower aldosterone production in vesseles as well as an increase in vascular responses to norepinephrine.

关 键 词：高血压 羟甾类脱氢酶类 甘草甜素 治疗 药理 

分 类 号：R544.105[医药卫生—心血管疾病] R972.4[医药卫生—内科学]