Inflammatory reaction versus endogenous peroxisome proliferator-activated receptors expression, re-exploring secondary organ complications of spontaneously hypertensive rats
Inflammatory reaction versus endogenous peroxisome proliferator-activated receptors expression, re-exploring secondary organ complications of spontaneously hypertensive rats
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DOI：
10.1097/00029330-200811020-00017
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发表时间：
2008-11-20
影响因子：
6.1
通讯作者：
Bian Ka
中科院分区：
文献类型：
--
作者：
Sun Li;Ke Yan;Bian Ka
背景高血压病的慢性血管壁病变可对多个器官系统产生破坏性影响。越来越多的证据表明，炎症反应参与了高血压的病理变化。目前已鉴定出三种PPAR受体：PPARα、PPARβ/Delta和PPARγ，它们都具有多种生物学效应，尤其是抑制炎症反应。为了解炎症状态下PPAR亚型在自发性高血压大鼠(SHR)重要脏器中的表达情况，了解炎症状态下内源性PPAR亚型的变化规律。方法取自发性高血压大鼠(SHR)和年龄匹配的Wistar-京都大鼠(WKY)的肾脏、肝脏、心脏和脑组织，观察PPAR异构体和PPAR反应基因(酰辅酶A氧化酶和CD36)的丰度。此外，还观察到可反式激活PPARγ表达的CCAAT/增强子结合蛋白Delta(C/EBP Delta)的表达。通过炎症介质诱导型一氧化氮合酶(INOS)、细胞间黏附分子-1(ICAM-1)、血管细胞黏附分子-1(VCAM-1)、E-选择素、白介素1-β(IL-1β)和肿瘤坏死因子α(TNF-α)的表达，以及羰基和硝化蛋白的形成来分析炎症反应。结果与WKY相比，SHR的3种PPAR亚型和PPAR反应基因的表达明显上调。其中，肾、肝、心和脑中PPARα蛋白的表达分别增加了130.76%、91.48%、306.24%和90.70%；PPARβ/Delta增加了109.34%、161.98%、137.04%和131.66%；PPARγ增加了393.76%、193.17%、559.29%和591.18%。与PPAR-γ的变化相一致，自发性高血压大鼠C/EBP Delta的表达也显著升高。与WKY组相比，SHR各脏器炎性介质的表达均显著增加。结论自发性高血压大鼠各脏器炎症反应增强，可能在高血压及继发性脏器并发症的发病机制中起关键作用。PPAR表达的改变(增加)可能反映了高血压大鼠炎症状态的代偿机制。
Background The chronic pathological changes in vascular walls of hypertension may exert destructive effects on multiple organ systems. Accumulating evidence indicates that inflammatory reactions are involved in the pathological changes of hypertension. Three peroxisome proliferator-activated receptors (PPARs) have been identified: PPAR alpha, PPAR beta/delta, and PPAR gamma, all of which have multiple biological effects, especially the inhibition of inflammation. The aim of this study was to evaluate PPAR isoforms expression profile in important organs of spontaneously hypertensive rats (SHR) and to understand the modulation of endogenous PPAR isoforms under inflammatory condition.Methods Tissues (kidney, liver, heart, and brain) were dissected from SHR and age-matched control Wistar-Kyoto rats (WKY) to investigate the abundance of PPAR isoforms and PPAR-responsive genes (acyl-CoA oxidase and CD36). The expression of CCAAT/enhancer-binding protein delta (C/EBP delta), which can trans-activate PPAR gamma expression, was also observed. The inflammatory response was analyzed by the expression of inflammatory mediators inducible nitric oxide synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, interleukin-1 beta (IL-1 beta), and tumor necrosis factor alpha (TNF alpha), and formation of carbonyl and nitrated proteins.Results The expressions of 3 PPAR isoforms and PPAR-responsive genes were markedly upregulated in SHR compared with those of WKY. Specifically, the expression of PPARa protein in the kidney, liver, heart and brain increased by 130.76 %, 91.48%, 306.24%, and 90.70%; PPAR beta/delta upregulated by 109.34%, 161.98%, 137.04%, and 131.66%; PPAR gamma increased by 393.76%, 193.17%, 559.29%, and 591.18%. In consistent with the changes in PPAR gamma, the expression of C/EBP delta was also dramatically elevated in SHR. Inflammatory mediators expressions were significantly increased in the most organs of SHR than WKY. As a consequence, increased formation of carbonyl and nitrated proteins were also observed in the most organs of SHR.Conclusions These findings suggest an enhanced inflammatory response in the organs of SHR, which might play a key role in pathogenesis of hypertension and secondary organ complications. Changes (increases) in PPARs expression may reflect a compensatory mechanism to the inflammatory status of hypertensive rats.