微量元素锶对幼年自发性高血压大鼠血压升高的预防作用及其作用机制探讨

Effect of Trace Element Strontium Prevention on Juvenile Spontaneously Hypertensive Rats Elevated Blood Pressure and the Mechanism

目的:研究微量元素锶对幼年自发性高血压大鼠(Spontaneously hypertensive rats,SHR)血压升高的预防作用并探讨其作用机制。方法:107只自发性高血压大鼠适应性喂养1周后,随机分为A组纯水对照组22只、B组锶水浓度3mg/L组22只、C组锶水浓度9mg/L组19只、D组锶水浓度18mg/L组22只,E组锶水浓度36mg/L组22只,普通饲料喂养12周。实验开始时测定基础血压,至结束时共测十次血压。实验开始及结束采血两次,检测肝、肾功能,Elisa法检测血清内皮素-1(endothelin-1,ET-1)、肾素(renin)、血管紧张素I(Iangiotensin-II)及去甲肾上腺素(noradrenalin,NA),免疫组化法检测主动脉核因子κB(nuclear factor-kappa B,NF-κB)、血管细胞黏附分子-1(vascular cell adhesion molecule-1,VCAM-1)、细胞间黏附分子-1(intercellular cell adhesion molecule-1,ICAM-1)的表达。结果:(1)SHR成年后,E组与A组相比表现出血压下降趋势(P<0.05);第十、十一、十二周时D、E组血压均显著低于A组(P<0.01);B、C组较A组也有不同程度下降;随锶水浓度增高血压呈逐渐下降的大体趋势,B-E组血压值低于A组(P<0.05,P<0.01);(2)锶水喂养后各组肝、肾功能指标及ET-1、renin、Ang-II、NA变化无明显差异(P>0.05);(3)锶水喂养后,B-E组主动脉NF-κB、VCAM-1;ICAM-1的积分光密度值(IOD)均显著低于A组(P<0.01),且随锶水浓度增高,NF-κB、VCAM-1、ICAM-1的表达呈递减趋势(P<0.01)。结论:微量元素锶可延缓SHR血压升高,减小血压波动,其对高血压的预防作用机制可能是由于抑制NF-κB经典通路,减少VCAM-1、ICAM-1等炎症介质的产生而减轻血管壁损害。

Objective： To investigate the effects of Trace element strontium prevention on Juvenile spontaneously hypertensive rats （SHR） elevated blood pressure and the mechanism. Methods： One hundred and seven SHR were randomly divided into five groups from A to E after one-week adaptive feeding：the pure water control group （n=22）, the strontium water concentration 3mg/L group （n=22）, the strontium water concentration 9mg/L group （n=l 9）, the strontium water concentration 18mg/L group （n=22）, and the strontium water concentration 36mg/L group （n=22）. Normal diet was fed to all rats for twelve weeks. Each group was measured basal blood pressure in the beginning of the experiment. To the end, there were a total of ten blood pressure measurements. At the starts and the ends of the experiment, liver function and renal function were detected.. Serum endothelin-1, rennin, angiotensin-II and noradrenalin were tested by Elisa. NF-KB, VCAM-1 and ICAM-1 levels of aortic were detected by immunohistochemical method. Results： （1） When SHR become adults, group E began to show a trend of decrease in blood pressure compared with group A （P〈0.05）.Group D and E blood pressure are significantly lower than group A in the tenth, eleventh, and twelfth weeks（P〈0.01）. Blood pressure in Group B and C declined compared with that in group A,. With the increasing of the strontium water concentration, blood pressure showed a gradual decline in the general trend. In group B-E, blood pressure was lower than that in group A （P〈0.05,P〈0.01）. （2） Among all groups, there was no significant difference in liver function, renal function, ET-1, renin, Ang-II and NA after the feeding of strontium water（P〈0.05）. （3） The integrated optical density（IOD）ofNF-KB, VCAM-1, and ICAM-1 in aorta of group B-E are significantly lower than that in group A（P〈0.01）. The NF-KB, VCAM-1 and ICAM-1 expression showed a decreasing trend accompanied with the increasing of strontium water concentration （P 〈 0.01）. Conclusions： Trace elements strontium can delay the rise of SHR blood pressure and reduce the fluctuation of blood pressure. Its hypertension prevention mechanism may be due to inhibition of the classical pathway of NF-KB by decreasing VCAM-1, ICAM-1 and other inflammatory factors to reduce the blood vessel wall damage.