葛根素对自发性高血压大鼠胸主动脉结构和功能的影响

摘要

目的 探讨葛根素对自发性高血压大鼠(SHR)胸主动脉结构和功能的影响及其降压机制.方法 12周龄SHR适应性喂养及血压测量训练1周后,ip给予葛根素25,50和100 mg· kg-1,给药6周.以第1次给药为第1周初,分别于给药前及给药后第2,4和6周测量血压.用硝酸还原酶法检测血清一氧化氮(NO)含量,放免法测量血浆内皮素1(ET-1)含量；HE染色观察胸主动脉形态学改变.制备胸主动脉环,采用累积加药法检测各组动脉环对苯肾上腺素(PE)10-9 ～ 10-5 mol·L-1及乙酰胆碱(ACh) 10-7～10-3 mol·L-1引起的收缩或舒张反应.结果 与对照组WKY大鼠相比,SHR模型组血压升高,ET-1增多,NO减少(P＜0.01)；血管肌层有大量脂质及纤维组织沉积,内皮边缘粗糙不平滑.与SHR模型组相比,葛根素25,50和100 mg· kg -1组血压分别降低了6.7±1.0,5.1±0.6和(2.2 ±0.3) kPa,差异显著(P＜0.05)；葛根素100 mg·kg-1组NO含量升高了1倍(P＜0.01),ET-1含量降低了(36.3±4.2)％(P＜0.05)；血管肌层增生及脂质、纤维组织浸润明显好转,内皮也较平滑；降低PE对胸主动脉的收缩程度(P＜0.05),增大ACh对胸主动脉的舒张程度(P＜0.05).结论 葛根素对SHR具有良好的降压作用.其降压机制可能与其减弱SHR血管肾上腺素受体敏感性、保护血管内皮、增加血管内皮依赖性舒血管作用及纠正血液中血管舒缩因子失衡有关.%OBJECTIVE To observe the effect of puerarin on the relaxing and contracting factors in blood and on structure and function of thoracic artery rings in vitro in spontaneously hypertensive rats (SHRs) so as to explore its antihypertensive mechanisms.METHODS After 12-week-old male SHRs were adaptively fed and blood pressure was practically measured for one week,puerarin 25,50,and 100 mg·kg-1 was given intraperitoneally for six weeks.In addition,SHR and WKY control groups were set up.Each group contained 7 rats.The first administration was regarded as the start of the first week.Blood pressure was measured at baseline,2nd,4th and 6th week.Contents of endothelin-1 (ET-1) in plasma and nitric oxide (NO) in serum were detected by radioimmunoassay and nitric acid reductase,respectively.Changes in morphology of the thoracic aorta were observed by HE staining.The response of the thoracic aorta to phenephrine (PE)10-9 - 10-5 mol·L- 1 or acetylcholine (ACh)10-7 -10-3 mol· L-1 was measured with an additive concentration method.RESULTS Compared with WKY group,blood pressure increased in SHR model group ; content of ET-1 increased and that of NO decreased ( P ＜0.01 ) ; fibrous tissue was proliferated within the vascular layer with large lipid and fibrous deposits,and the verge of endodermis was rough.compared with SHR model group,puerarin 25,50,100 mg· kg-1 significantly lowered blood pressure by 6.7 ± 1.0,5.1 ± 0.6 and (2.2 ± 0.3 ) kPa,respectively ( P ＜ 0.05).The level of NO doubled (P ＜0.01 ) and that of ET-1 decreased by (36.3 ±4.2)％ (P ＜0.05) in puerain 100 mg·kg-1 group; smooth muscle proliferation and lipid and fibrous deposits in the thoracic aorta improved; contractile response to PE decreased (P ＜ 0.05) and relaxation response to ACh increased ( P ＜ 0.05 ).CONCLUSION Puerarin has a substantial antihypertensive effect on SHRs,and its mechanism may be related to reducing sensitivity of the vessels to catecholamines,protecting vascular endothelium,increasing endothelium-dependent relaxation and improving the disequilibrium between vasodilating and vasoconstricting substances.