CAJ | 학술논문

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.
목적 통과관찰경도혈뇨산승고대대서신소구내피세포공능손상급혈관평활기세포증식적영향,탐토경도혈뇨산승고시부능도치신장손해급강뇨산치료대신장적보호작용.방법 용웅성SD대서위연구대상,수궤분위4조:대조조(n=15)、양진산조(n=15)、별표령순조(n=12)화양진산+별표령순조(n=12).여이저염음식,매격10천감측각조대서적동맥혈압.우시험후20 d급40 d용ELISA법분별측정각조대서내피세포공능수손적지표[일양화담(NO)、내피소(ET)1、섬용매원격활물(PAI)1]、혈관평활기세포증식적지표[혈소판연생인자(PDGF)、배양화매(COX)2、단핵세포추화단백(MCP)1적함량]이급염성반응지표[백세포개소(IL)18、종류배사인자(TNF)α]；동시관찰각조대서신공능급신장조직병리변화；면역조화법검측각조대서신조직중PDGF、일양화담합매(NOS)적표체.결과 여대조조상비,양진산조대서혈장NO농도현저강저(P＜0.05),ET-1、PAI-1、PDGF、MCP-1、COX2、TNF-α、IL-18농도균현저승고(균P＜ 0.05).광경하,각조대서신조직균미견뇨산결정형성,양진산조신소혈관관벽증후,내막증생,관강협착；면역조화결과현시,여대조조상비,양진산조NOS적표체현저감소(7.33％±2.11％비25.75％±2.33％,P＜0.05),PDGF적표체현저증다(31.18％±2.83％비8.09％±1.81％,P＜ 0.05).경별표령순강뇨산간예치료후대서혈청중내피세포손상지표NO상조(P＜0.05),이ET-1급PAI-1균하조(균P＜0.05)；이혈관평활기증식지표급염성지표균하조(균P＜ 0.05).결론 경도혈뇨산승고가도치신소구내피세포공능수손、혈관평활기세포증식；강뇨산치료능개선내피세포공능,감경혈관평활기세포적증식.
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 muscle[plateletderived growth factor (PDGF),cycloxygenase 2 (COX2),monocyte chemotactic protein-1 (MCP-1)],and the markers of inflammatory reaction[interleukin-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-o,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.