实验性慢性肾病中的炎症、营养不良与血管收缩

Inflammation, malnutrition and vascular contraction in experimental chronic kidney disease.

作者信息

Brymora Andrzej, Flisiński Mariusz, Grześk Grzegorz, Szadujkis-Szadurski Leszek, Odrowaz-Sypniewska Grazyna, Manitius Jacek

机构信息

Department of Nephrology, Hypertension and Internal Diseases, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Torun, Poland.

出版信息

J Nephrol. 2007 Jul-Aug;20(4):423-9.

PMID:17879208

Abstract

BACKGROUND

Inflammation is a well-defined factor influencing the development of cardiovascular complications in chronic renal failure. The aim of this study was to examine systemic inflammatory state defined by the level of serum haptoglobin, local inflammation defined by monocyte chemoattractant protein-1 (MCP-1) level and arterial response to phenylephrine in different stages of renal failure.

METHODS

Experiments were performed on male Wistar rats, weighing 290-380 g. The rats were divided into 4 groups: I (control) was shame-operated (n=12); II underwent 1/2 nephrectomy (n=12); III, 3/4 nephrectomy (n=8); IV 5/6 nephrectomy (n=12). After 4 weeks, blood pressure (BP) in carotid artery was measured, and blood was collected for blood urea nitrogen, creatinine, albumin, haptoglobin and MCP-1. We compared the smooth muscle contractility after stimulation of alpha1-adrenoreceptor with phenylephrine in all groups. The constriction of artery was measured as the increase in perfusion pressure at a constant flow of the perfusion fluid. Cumulative response curves (CRCs) were obtained using the van Rossum method.

RESULTS

We observed a significant shift of CRCs to the left in group III (calculated half-maximal contraction [EC50] was 1.55 x 10(-7) M/L vs. 7.71 x 10(-7) M/L in control) and a nonsignificant shift of CRCs to the left in group II (3.62 x 10(-7) M/L). Unexpectedly, rat tail arteries from the rats in the 5/6 nephrectomy group were characterized by diminished contraction response to phenylephrine (EC50 9.57 x 10-7 M/L). Systemic inflammation defined by haptoglobin level occurred in the 1/2 nephrectomy group and did not increase in more advanced stages of renal disease. Local inflammation (MCP-1 level) increased together with the renal failure progression. We found a positive correlation between MCP-1 level and haptoglobin only in the 5/6 nephrectomy group (r=0.65; p<0.01).

CONCLUSION

The inflammatory state which affects vascular smooth muscle cells plays a key role in determining vascular contraction and resistant artery tone.

摘要

背景

炎症是影响慢性肾衰竭心血管并发症发生发展的一个明确因素。本研究旨在探讨由血清触珠蛋白水平定义的全身炎症状态、由单核细胞趋化蛋白-1（MCP-1）水平定义的局部炎症以及肾衰竭不同阶段动脉对去氧肾上腺素的反应。

方法

实验在体重290 - 380 g的雄性Wistar大鼠身上进行。大鼠被分为4组：I组（对照组）进行假手术（n = 12）；II组行1/2肾切除术（n = 12）；III组行3/4肾切除术（n = 8）；IV组行5/6肾切除术（n = 12）。4周后，测量颈动脉血压（BP），并采集血液检测血尿素氮、肌酐、白蛋白、触珠蛋白和MCP-1。我们比较了所有组中用去氧肾上腺素刺激α1 - 肾上腺素能受体后平滑肌的收缩性。动脉收缩以灌注液恒定流速下灌注压力的升高来衡量。使用范罗森方法获得累积反应曲线（CRC）。

结果

我们观察到III组的CRC显著左移（计算得出的半数最大收缩浓度[EC50]为1.55×10⁻⁷M/L，而对照组为7.71×10⁻⁷M/L），II组的CRC有不显著的左移（3.62×10⁻⁷M/L）。出乎意料的是，5/6肾切除组大鼠的鼠尾动脉对去氧肾上腺素的收缩反应减弱（EC50为9.57×10⁻⁷M/L）。由触珠蛋白水平定义的全身炎症在1/2肾切除组出现，在更晚期的肾脏疾病中并未增加。局部炎症（MCP-1水平）随肾衰竭进展而增加。我们仅在5/6肾切除组发现MCP-1水平与触珠蛋白之间存在正相关（r = 0.65；p < 0.01）。