轻度血尿酸升高对大鼠肾小球内皮细胞及血管平滑肌细胞功能的影响

目的 通过观察轻度血尿酸升高对大鼠肾小球内皮细胞功能损伤及血管平滑肌细胞增殖的影响,探讨轻度血尿酸升高是否能导致肾脏损害及降尿酸治疗对肾脏的保护作用.方法 用雄性SD大鼠为研究对象,随机分为4组:对照组(n=15)、氧嗪酸组(n=15)、别嘌呤醇组(n=12)和氧嗪酸+别嘌呤醇组(n=12).予以低盐饮食,每隔10天监测各组大鼠的动脉血压.于试验后20 d及40 d用ELISA法分别测定各组大鼠内皮细胞功能受损的指标一氧化氮(NO)、内皮素(ET)1、纤溶酶原激活物(PAI)1]、血管平滑肌细胞增殖的指标血小板衍生因子(PDGF)、环氧化酶(COX)2、单核细胞趋化蛋白(MCP)1的含量]以及炎性反应指标白细胞介素(IL)18、肿瘤坏死因子(TNF)α]；同时观察各组大鼠肾功能及肾脏组织病理变化；免疫组化法检测各组大鼠肾组织中PDGF、一氧化氮合酶(NOS)的表达.结果 与对照组相比,氧嗪酸组大鼠血浆NO浓度显著降低(P＜0.05),ET-1、PAI-1、PDGF、MCP-1、COX2、TNF-α、IL-18浓度均显著升高(均P＜ 0.05).光镜下,各组大鼠肾组织均未见尿酸结晶形成,氧嗪酸组肾小血管管壁增厚,内膜增生,管腔狭窄；免疫组化结果显示,与对照组相比,氧嗪酸组NOS的表达显著减少(7.33％±2.11％比25.75％±2.33％,P＜0.05),PDGF的表达显著增多(31.18％±2.83％比8.09％±1.81％,P＜ 0.05).经别嘌呤醇降尿酸干预治疗后大鼠血清中内皮细胞损伤指标NO上调(P＜0.05),而ET-1及PAI-1均下调(均P＜0.05)；而血管平滑肌增殖指标及炎性指标均下调(均P＜ 0.05).结论 轻度血尿酸升高可导致肾小球内皮细胞功能受损、血管平滑肌细胞增殖；降尿酸治疗能改善内皮细胞功能,减轻血管平滑肌细胞的增殖.

Influence of mild hyperuricemia on the function of glomerular endothelial cells and vascular smooth muscle cells in rats

Objective To discuss whether mild hyperuricemia can lead to kidney damage and the protection of decreased uric acid, through observing that hyperuricemia did damage to glomerulus endothelial function and cell proliferation of vascular smooth muscle in rats. Methods Fifty-four male SD rats were divided into four groups, the control group, model group (Oxonate), allopurinol group and Oxonate＋allopurinol group. Rats were administered on a low sodium diet and their systolic blood pressure (SBP) were measured each 10 days. ELISA was used to detect rat plasma markers of endothelial function damage nitric oxide (NO), type-1 plasminogen activator inhibitor(PAI-1), endothelin 1(ET-1)] and cell proliferation of vascular smooth muscleplatelet-derived growth factor (PDGF), cycloxygenase 2 (COX2), monocyte chemotactic protein-1(MCP-1)], and the markers of inflammatory reactioninterleukin-18 (IL-18), tumor necrosis factor α(TNF-α)]. PDGF and nitric oxide synthase (NOS) levels of rats were detected by immunohistochemical method. Renal tissue pathology of rats was observed. Results Compared to the control group, the plasmic concentration of COX2, ET-1, IL-18, PAI-1, PDGF, TNF-α, MCP-1 increased, and NO decreased significantly in rats of model group (all P＜0.05), expression of NOS significantly reduced and PDGF increased (all P＜0.05). Under light microscope, vascular wall thickening, intimal proliferation and lumen slight stricture without uric acid crystals in renal tissue were found in model group, which were obviously improved by using allopurinol. Conclusion Mild hyperuricemia can do damage to endothelial function of glomerulus and lead to vascular cell proliferation, which can be improved through decreasing uric acid.