Ruiz-Ortega Marta, Ruperez Mónica, Lorenzo Oscar, Esteban Vanesa, Blanco Julia, Mezzano Sergio, Egido Jesus
Laboratory of Vascular and Renal Pathology, Fundación Jiménez Díaz, Universidad Autónoma, Hospital Clínico, Madrid, Spain.
Kidney Int Suppl. 2002 Dec(82):S12-22. doi: 10.1046/j.1523-1755.62.s82.4.x.
Emerging evidence suggests that angiotensin II (Ang II) is not only a vasoactive peptide, but also a true cytokine that regulates cell growth, inflammation and fibrosis. Many studies have demonstrated that this peptide plays an active role in the progression of renal injury. Some of Ang II-induced effects are mediated by the production of a large array of growth factors. The aim of this study was to investigate whether Ang II could regulate the expression of cytokines and chemokines in the kidney and its correlation with the Ang II-induced renal damage.
The model of Ang II-induced renal damage was done by systemic Ang II infusion into normal rats (50 ng/kg/min; subcutaneous osmotic minipumps). In addition, the implication of Ang II was investigated in a model of immune complex nephritis in rats treated with the angiotensin converting enzyme (ACE) inhibitor quinapril. The mRNA expression was analyzed by RT-PCR and/or Northern blot, and protein levels by Western blot and/or immunohistochemistry.
Rats infused with Ang II for 3 days caused elevated renal expression of tumor necrosis factor-alpha (TNF-alpha; gene and protein levels). TNF-alpha positive cells were observed in glomeruli (mainly in endothelial cells), tubules and vessels. In rats with immune complex nephritis, the renal overexpression of TNF-alpha was diminished by the ACE inhibitor quinapril. Systemic infusion of Ang II also increased renal synthesis of cytokines (interleukin-6, IL-6) and chemokines (monocyte chemoattractant protein-1; MCP-1) that were associated with elevated tissue levels of activated nuclear factor-kappaB (NF-kappaB) and the presence of inflammatory cell infiltration.
Ang II in vivo increases TNF-alpha production in the kidney. Ang II also up-regulates other proinflammatory mediators, including IL-6, MCP-1 and NF-kappaB, coincidentally associated to the presence of glomerular and interstitial inflammatory cells in the kidney. All these data further strengthen the idea that Ang II plays an active role in the inflammatory response in renal diseases.
新出现的证据表明，血管紧张素II（Ang II）不仅是一种血管活性肽，还是一种真正的细胞因子，可调节细胞生长、炎症和纤维化。许多研究表明，这种肽在肾损伤进展中发挥积极作用。Ang II诱导的一些效应是由大量生长因子的产生介导的。本研究的目的是探讨Ang II是否能调节肾脏中细胞因子和趋化因子的表达及其与Ang II诱导的肾损伤的相关性。
通过向正常大鼠体内系统性输注Ang II（50 ng/kg/分钟；皮下渗透微型泵）建立Ang II诱导的肾损伤模型。此外，在接受血管紧张素转换酶（ACE）抑制剂喹那普利治疗的大鼠免疫复合物肾炎模型中研究了Ang II的作用。通过逆转录聚合酶链反应（RT-PCR）和/或Northern印迹分析mRNA表达，通过蛋白质印迹和/或免疫组织化学分析蛋白质水平。
向大鼠输注Ang II 3天导致肾脏肿瘤坏死因子-α（TNF-α；基因和蛋白质水平）表达升高。在肾小球（主要在内皮细胞）、肾小管和血管中观察到TNF-α阳性细胞。在免疫复合物肾炎大鼠中，ACE抑制剂喹那普利可降低肾脏中TNF-α的过度表达。系统性输注Ang II还增加了肾脏中细胞因子（白细胞介素-6，IL-6）和趋化因子（单核细胞趋化蛋白-1；MCP-1）的合成，这与活化核因子-κB（NF-κB）组织水平升高和炎症细胞浸润有关。
体内Ang II增加肾脏中TNF-α的产生。Ang II还上调其他促炎介质，包括IL-6、MCP-1和NF-κB，同时与肾脏中肾小球和间质炎症细胞的存在有关。所有这些数据进一步强化了Ang II在肾脏疾病炎症反应中发挥积极作用的观点。
