过氧化物酶体增殖物激活受体-γ在自发性高血压大鼠胸主动脉的表达和瑞舒伐他汀干预作用

Expression of peroxisome proliferator-activated receptor gamma and effect of rosuvastatin on thoracic aorta remodeling in spontaneous hypertensive rats

目的探讨过氧化物酶体增殖物激活受体-γ(PPAR-γ)在自发性高血压大鼠(SHR)胸主动脉的表达和瑞舒伐他汀(ROS)的干预作用。方法 16只6周龄健康雄性SHR随机分入SHR组和ROS组,每组8只;另选8只同龄雄性Wistar-Kyoto大鼠(WKY)作为对照(WKY组),喂养8周后抽取血液,处死,获取胸主动脉段,行苏木精-伊红染色并应用计算机图像分析系统测量中膜厚度/管腔内径(MT/LD)、中膜面积/管腔面积(MA/LA)比值,以双抗体夹心生物素-亲和素酶联免疫吸附试验测定法检测血清白细胞介素(IL)-6、肿瘤坏死因子(TNF)-α、高敏C反应蛋白(hs-CRP)水平,取主动脉组织采用实时定量聚合酶链反应和Western印迹法测定PPAR-γ基因和蛋白表达水平。结果 SHR组10、14周龄的收缩压均显著高于同组6周龄(P值均<0.01),而WKY组、ROS组不同周龄间收缩压的差异均无统计学意义(P值均>0.05)。SHR组6、10、14周龄的收缩压均显著高于WKY组同周龄(P值均<0.01),而ROS组10、14周龄的收缩压均显著低于SHR组同周龄(P值均<0.01)。SHR组的血清IL-6、TNF-α、hs-CRP水平,以及MT/LD、MA/LA比值均显著高于WKY组和ROS组(P值分别<0.05、0.01),ROS组与WKY组间差异均无统计学意义(P值均>0.05)。SHR组PPAR-γmRNA、蛋白表达水平显著高于WKY组(P值均<0.01),但显著低于ROS组(P值均<0.01)。结论PPAR-γ可能与高血压血管重构有关,ROS可抑制炎症,促进血管中的PPAR-γ表达,改善血管重塑。

Objective To investigate the expression of peroxisome proliferator-activated receptor gamma （PPAR-γ） and the effect of rosuvastatin on thoracic aorta remodeling in spontaneous hypertensive rat （SHR）. Methods Sixteen SHRs were randomly divided into SHR group （n = 8） and rosuvastatin （ROS） group （n = 8）. Eight age-matched male Wistar-Kyoto （WKY） rats were taken as controls. The animals were sacrificed after eightweek treatment. The ratios of media thickness to lumen diameter （MT/LD） and media area to lumen area （MA/ LA） of thoracic aorta were measured by computer image analysis. Serum levels of interleukin-6 （IL-6）, tumor necrosis factor （TNF）-α, all high sensitivity C-reactive protein （hs-CRP） were detected by ARC-enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein expression of thoracic aortic PPAR-γ were detected with real-time-polymerase chain reaction and Western blot, respectively. Results Systolic pressure in 10- and 14- week SHRs were significantly higher than that in 6-week SHRs （both P 〈 0. 01 ）. But there was no significant difference in systolic pressure between rats of different ages in both WKY group and ROS group （all P〉0.05）. Systolic pressure in SHR group were significantly higher than those in WKY group at the age of 6, 10 and 14 weeks （all P〈0.01）, while systolic pressure in ROS group were significantly lower than that in SHR group at the age of 10 and 14 weeks （all P〉0.01）. Serum levels of IL-6, TNF-α and hs-CRP in SHR group were significantly higher than those in WKY group and ROS group （all P〈0.05）, so were MT/LD and MA/LA （all P〈0.01 ）. Compared with SHR group, the expression of PPAR-γ mRNA and protein of thoracic aorta were significantly increased in ROS group and decreased in WKY group （all P〈0.01）. Conclusion PPAR-γ is likely to be related to vascular remodeling. Rosuvastatin can increase the expression of PPAR-γ and improve vascular remodeling so as to inhibit inflammatory reaction in SHRs.