自发性高血压大鼠多组织炎症状态(英文)

Inflammation of different tissues in spontaneously hypertensive rats

高血压是一种慢性血管性疾病,易累及肾、肝、心、脑等组织,引起脑卒中和心、肾损害等并发症。本研究对高血压时肾、肝、心、脑等组织的炎症状态进行了观察。实验采用自发性高血压大鼠(spontaneously hypertensive rat,SHR)和正常血压的Wistar-Kyoto(WKY)大鼠,用RT-PCR和Western blot法观察肾、肝、心、脑等组织炎症相关因子IL-1β、TNFα、ICAM-1、iNOS、C/EBPδ和PPARγ的基因表达：紫外分光光度法观察蛋白质羰基化水平和FRAP法检测组织总抗氧化能力。结果显示：(1)SHR组织炎症相关因子表达较对照WKY增强,除IL-1βmRNA在肝和脑的增加不明显外,其余均有显著性差异(P＜0．05)；(2)SHR和WKY大鼠肾、心、脑蛋白质羰基化水平(nmol/mg蛋白)分别为8．93±1．08和2．27±0．43、2．23±0．23和0．17±0．02、13．42±1．10和5．72±1．01,SHR明显增加(P＜0．05)；而肝脏蛋白质羰基化水平无明显变化：(3)SHR肾、肝、心、脑总抗氧化能力水平显著低于WKY大鼠(P＜0．05)。以上结果表明,SHR多个组织(肾、肝、心和脑)均存在炎症因子被诱导和氧化应激反应等明显的炎症状态,提示炎症可能在高血压及其并发症的病理改变中起重要作用。

The hypertension is one of chronic vascular diseases, which often implicates multiple tissues causing stroke, cardiac hypertrophy, and renal failure. A growing body of evidence suggests that inflammatory mechanisms are important participants in the pathophysiology of hypertension. In this study, the inflammatory status of these tissues （kidney, liver, heart, and brain） in spontaneously hypertensive rats （SHR） was analyzed and its molecular mechanism was explored. The tissues were dissected from SHR and agematched control Wistar-Kyoto （WKY） rats to investigate the abundance of inflammation-related mediators （IL- 1β, TNFα, ICAM-1, iNOS, C/EBPδ and PPARγ）. mRNA levels were determined by reverse transcription-polymerase chain reaction and protein expression was evaluated by Western blot. To evaluate the oxidative stress of tissues, carbonyl protein content and total antioxidant capacity of tissues were detected by spectrophotometry and ferric reduction ability power （FRAP） method. The results suggest that： （1） Expressions of inflammation-related mediators （IL-1β, TNFα, ICAM-1, iNOS, C/EBPδ and PPARγ） in SHR were higher compared with those in WKY rats except no evident increase of IL-1β mRNA in liver and brain in SHR. （2） Tissues in SHR contained obviously increased carbonyl protein （nmol/mg protein） compared to that in WKY rats （8.93±1.08 vs 2.27±0.43 for kidney, 2.23±0.23 vs 0.17±0.02 for heart, 13.42±1.10 vs 5.72± 1.01 for brain, respectively, P〈0.05）. However, no evident difference in the amount of carbonyl protein in liver was detected between SHR and WKY rats. （3） Total antioxidant capacities of kidney, liver, heart and brain were markedly lower in SHR than that in WKY rats （P〈0.05）. Thus, the present data reveal a higher inflammatory status in the important tissues in SHR and indicate that inflammation might play a potential role in pathogenesis of hypertension and secondary organ complications.