Pawlaczyk K, Polubinska A, Numata N, Nakayama M, Pecoits-Filho R, Czekalski S, Lindholm B, Breborowicz A
Department of Pathophysiology and Nephrology, Poznan Medical School, Poznan - Poland.
Int J Artif Organs. 2008 Jun;31(6):535-44. doi: 10.1177/039139880803100609.
Peritoneal inflammation may induce changes in peritoneal microvessels, including neoangiogenesis/vasculogenesis, leading to increased peritoneal solute transport rate (PSTR) and loss of ultrafiltration capacity. We hypothesized that an inflammatory reaction in the peritoneal cavity during peritonitis induces increased synthesis of vascular endothelial growth factor (VEGF). We therefore studied the relationship between peritoneal inflammation markers, VEGF, and transport of fluid and solutes in rats during acute peritoneal inflammation induced by lipopolysaccharide (LPS) added to standard glucose-based dialysis solution.
Under ether anesthesia, male Wistar rats were injected intraperitoneally with 30 mL Dianeal 3.86% without (Control; n=6) or with LPS (microg/mL): 0.001 (LPS 0.001; n=6), 0.01 (LPS 0.01; n=7), 0.1 (LPS 0.1; n=7), 1.0 (LPS 1.0; n=8). After 8 hours, dialysate volume (IPV), peritoneal solute transport rate (PSTR) and dialysate cell count (DCC) were measured and effluent samples were collected.
LPS i.p. resulted in increased PSTR and decreased IPV (p<0.005). DCC (cells/microL) and the neutrophil/macrophage ratio were higher for all LPS concentrations compared to the control group. After 8 hours, LPS-exposed rats had significantly higher dialysate levels of all investigated cytokines (TNF-alfa, MCP-1 and IL-10) than the control group. Addition of LPS resulted in increased dialysate VEGF concentrations (pg/mL) (LPS 0.001, 28.2+/-5.9; LPS 0.01, 38.9+/-11.6; LPS 0.1, 43.0+/-5.9; LPS 1.0, 46.6+/-11.3; Control, 14.5+/-9.8; p<0.0005 for all LPS vs. Control).
The infusion of Dianeal 3.86% with different doses of LPS induced a strong acute intraperitoneal inflammatory reaction with increased DCC and cytokine levels, resulting in increased peritoneal solute transport and decreased IPV. LPS induced a dose-dependent parallel increase of the intraperitoneal concentrations of MCP-1, IL-10 and TNF-alfa, as well as of VEGF. These results suggest that intraperitoneal VEGF synthesis is induced in response to inflammation, and that this may be an important component in the process leading to peritoneal transport alterations.
腹膜炎症可引起腹膜微血管的变化，包括新生血管形成/血管生成，导致腹膜溶质转运率（PSTR）增加和超滤能力丧失。我们假设腹膜炎期间腹腔内的炎症反应会诱导血管内皮生长因子（VEGF）合成增加。因此，我们研究了在添加脂多糖（LPS）至标准葡萄糖基透析液所诱导的大鼠急性腹膜炎症期间，腹膜炎症标志物、VEGF与液体和溶质转运之间的关系。
在乙醚麻醉下，雄性Wistar大鼠腹腔内注射30 mL不含（对照组；n = 6）或含LPS（微克/毫升）的3.86% Dianeal：0.001（LPS 0.001；n = 6）、0.01（LPS 0.01；n = 7）、0.1（LPS 0.1；n = 7）、1.0（LPS 1.0；n = 8）。8小时后，测量透析液体积（IPV）、腹膜溶质转运率（PSTR）和透析液细胞计数（DCC），并收集流出液样本。
腹腔注射LPS导致PSTR增加和IPV降低（p < 0.005）。与对照组相比，所有LPS浓度组的DCC（细胞/微升）和中性粒细胞/巨噬细胞比值均更高。8小时后，LPS处理的大鼠所有研究细胞因子（TNF-α、MCP-1和IL-10）的透析液水平均显著高于对照组。添加LPS导致透析液VEGF浓度（皮克/毫升）增加（LPS 0.001，28.2±5.9；LPS 0.01，38.9±11.6；LPS 0.1，43.0±5.9；LPS 1.0，46.6±11.3；对照组，14.5±9.8；所有LPS组与对照组相比，p < 0.0005）。
输注含不同剂量LPS的3.86% Dianeal可诱导强烈的急性腹腔内炎症反应，DCC和细胞因子水平升高，导致腹膜溶质转运增加和IPV降低。LPS诱导腹腔内MCP-1、IL-10和TNF-α以及VEGF浓度呈剂量依赖性平行增加。这些结果表明，腹腔内VEGF合成是对炎症的反应性诱导，这可能是导致腹膜转运改变过程中的一个重要组成部分。
