The effects of Xuezhikang on vascular remodeling and aortic fibers in spontaneously hypertensive rats

Background Xuezhikang is a traditional Chinese medicine for the therapy of patients with cardiovascular diseases. However, the effect of Xuezhikang on vascular remodeling and aortic fibers in spontaneously hypertensive rats remains unclear. Methods Thirty spontaneously hypertensive rats(SHRs) aged 8 weeks were randomized into three groups: SHRs control group(SHRs group, n = 10), group treated with low dose Xuezhikang(XZK-L,20 mg/kg/d, n = 10) and group treated with high dose Xuezhikang(XZK-H, 200 mg/kg/d, n = 10). The normal group was comprised of ten Wistar-Kyoto(WKY) rats of the same age. While under pentobarbital anesthesia, in vivo aortic stiffness was determined by a pulse wave velocity(PWV) technique and measured locally in the descending thoracic aorta by Doppler ultrasound echocardiography. Fixed tissues were sectioned and stained with hematoxylin and eosin, masson trichrome, aldehyde-fuchsin and Gordon-Sweets stain. Results The PWV, thicknesses of the aortic wall, wall-to-lumen(W/L) ratio, elastic fibers thicknesses and collagen volume fraction were measured. XZK-L and XZK-H groups were observed to be significantly greater than those in the normal group(P 0.01). The levels of PWV, W/L ratio and collagen fibers were observed to be significantly reduced in the XZK-H group when compared with the control group(P 0.05). There was no significance in reticular fiber distributing between the XZK-treated group and SHR group. The reticular fibers in SHR rats were obviously more than those of WKY rats. Conclusion The hypertensive vascular remodeling is associated with changes of elastic fibers and collagen and reticular fibers. Xuezhikang improves hypertensive vascular remodeling by repairing the elastic fibers and inhibiting the levels of collagen.     

高血压合并降主动脉夹层患者血清Fibulin-3和肱-踝脉搏波传导速度的相关性研究

目的:探讨高血压合并主动脉夹层(aortic dissection,AD)患者血清Fibulin-3水平改变的临床意义及其与肱-踝脉搏波传导速度(branchial-ankle pulse wave velocity,baPWV)的相关性。方法:纳入广东药科大学附属第一医院心内科和广州军区广州总医院住院高血压合并AD(DebakeyⅢ型或Stanford B型)患者49例(高血压合并AD组),同时收集广东药科大学附属第一医院住院和门诊高血压患者60例(高血压组),以及体检的健康人48例(对照组)。以酶联免疫吸附(ELISA)方法检测血清Fibulin-3和基质金属蛋白酶9(MMP-9)表达;采用脉搏波速度自动测定仪测定baPWV。结果:高血压合并AD组血压水平、男性比例和吸烟比例均高于高血压组和对照组(均P0.05);高血压合并AD组血清Fibulin-3水平明显低于高血压组,而高血压组低于对照组(均P0.05);高血压合并AD组血清MMP-9水平明显高于高血压组(P0.05),而高血压组和对照组比较差异无统计学意义;高血压合并AD组baPWV水平明显高于高血压组和对照组,而高血压组高于正常组(均P0.05)。在高血压合并AD患者中,Fibulin-3与baPWV呈负相关性(r=-0.463,P0.01),MMP-9和baPWV无明显相关性。结论:高血压合并AD患者存在主动脉细胞外基质蛋白和MMP水平改变,动脉硬化指标水平升高,血清Fibulin-3、MMP-9水平和baPWV可作为高血压合并主动脉损害的指标之一,对评估血管功能改变有一定临床意义。     

赤芍总苷对高血压大鼠血管重构基质金属蛋白酶9、金属蛋白酶组织抑制因子1和血管壁氧化应激的干预作用

目的探讨赤芍总苷(TPG)对自发性高血压大鼠(SHR)血管重构基质金属蛋白酶9(MMP-9)、金属蛋白酶组织抑制因子1(TIMP-1)和血管壁氧化应激的干预作用。方法 30只8周龄雄性SHR大鼠随机分为3组:低剂量TPG组(低剂量组,n=10)、高剂量TPG组(高剂量组,n=10)、对照组(n=10);另外以Wistar大鼠作为空白组(n=8)。低剂量组、高剂量组分别以100、200 mg/(kg·d)的TPG灌胃,对照组、空白组以2 mL生理盐水灌胃。8周后,酶联免疫吸附测定法测定血清MMP-9、TIMP-1水平;活性氧(ROS)荧光探针检测胸主动脉壁细胞氧化应激水平;免疫组织化学染色检测主动脉MMP-9、TIMP-1蛋白表达。结果与空白组比较,对照组MMP-9、TIMP-1血清水平及血管壁MMP-9、TIMP-1蛋白表达均明显升高(P0.05)。TPG治疗后,MMP-9有所下降,高剂量组与对照组比较,差异有统计学意义(P0.05);但TIMP-1在低剂量组、高剂量组、对照组间差异无统计学意义(P0.05)。对照组胸主动脉ROS水平明显高于空白组,而低剂量组、高剂量组ROS水平较对照组下降。结论高血压血管重构存在血管氧化应激和MMP-9水平升高;TPG能够抑制动脉氧化应激和MMP-9水平,改善高血压血管重构,可作为高血压治疗的辅助药物。