Hilgers K F, Hartner A, Porst M, Mai M, Wittmann M, Hugo C, Ganten D, Geiger H, Veelken R, Mann J F
Department of Medicine IV, University of Erlangen-Nürnberg, Erlangen; Max-Delbrück-Center, Berlin-Buch, Germany.
Kidney Int. 2000 Dec;58(6):2408-19. doi: 10.1046/j.1523-1755.2000.00424.x.
We investigated whether monocyte chemoattractant protein-1 (MCP-1) is expressed in hypertensive nephrosclerosis, and tested the effect of angiotensin II type 1 receptor blockade on MCP-1 expression and macrophage (MPhi) infiltration.
Rats with two-kidney, one-clip (2K1C) hypertension with and without treatment with the angiotensin II type 1 receptor antagonist valsartan (3 mg/kg/day) were studied. In these animals as well as in spontaneously hypertensive rats (SHR), stroke-prone SHR (SHR-SP), hypertensive mRen-2 transgenic rats (TGR), and respective control strains, MCP-1 expression in the kidney was investigated by Northern and Western blots and by immunohistochemistry. Glomerular and interstitial MPhis were counted.
In the nonclipped kidney of 2K1C rats, MCP-1 expression was elevated at 14 and 28 days when significant MPhi infiltration was present. MCP-1 was localized to glomerular endothelial and epithelial cells, interstitial and tubular cells, MPhis, and vascular smooth muscle cells. A similar pattern of MCP-1 staining was present in TGR kidneys, whereas MCP-1 expression was not increased in SHR and SHR-SP. Valsartan reduced but did not normalize blood pressure, blocked the induction of MCP-1 protein in 2K1C kidneys, and decreased interstitial MPhi infiltration significantly.
MCP-1 expression is increased in angiotensin II-dependent models of hypertensive nephrosclerosis and is temporally and spatially related to MPhi infiltration. The angiotensin II type 1 receptor mediates the induction of MCP-1.
我们研究了单核细胞趋化蛋白-1（MCP-1）在高血压性肾硬化中是否表达，并测试了1型血管紧张素II受体阻断对MCP-1表达和巨噬细胞（MPhi）浸润的影响。
研究了两肾一夹（2K1C）高血压大鼠，分为接受和未接受1型血管紧张素II受体拮抗剂缬沙坦（3毫克/千克/天）治疗两组。在这些动物以及自发性高血压大鼠（SHR）、易中风SHR（SHR-SP）、高血压mRen-2转基因大鼠（TGR）和相应对照品系中，通过Northern和Western印迹以及免疫组织化学研究肾脏中MCP-1的表达。对肾小球和间质中的MPhi进行计数。
在2K1C大鼠的未夹闭肾脏中，当存在明显的MPhi浸润时，14天和28天时MCP-1表达升高。MCP-1定位于肾小球内皮细胞、上皮细胞、间质和肾小管细胞、MPhi以及血管平滑肌细胞。TGR肾脏中存在类似的MCP-1染色模式，而SHR和SHR-SP中MCP-1表达未增加。缬沙坦降低但未使血压正常化，阻断了2K1C肾脏中MCP-1蛋白的诱导，并显著减少了间质MPhi浸润。
在依赖血管紧张素II的高血压性肾硬化模型中，MCP-1表达增加，且在时间和空间上与MPhi浸润相关。1型血管紧张素II受体介导MCP-1的诱导。
