高尿酸血症肾病患者炎性因子IL-1β、IL-18表达的研究

Plasma levels of IL-1β and IL-18 in patients with urate nephropathy

目的高尿酸血症肾病与机体炎症反应密切相关,本研究比较炎性因子IL-1β和IL-18水平,探讨炎症因子在高尿酸血症肾病中的作用。方法收集2016年7月至2017年6月就诊于深圳市宝安医院成年男性患者作为研究对象,根据纳入及排除标准,分为高尿酸血症组、高尿酸血症肾病组及健康对照组,每组各15例。运用全自动生化分析仪器测定血生化指标血脂(总胆固醇、三酰甘油、低密度脂蛋白、高密度脂蛋白)、肾功能(肌酐、尿素氮)及血尿酸,运用尿液分析仪测定尿液常规检查(尿白细胞和尿红细胞),采用ELISA法测定各组血浆中IL-1β和IL-18。高尿酸血症组、高尿酸血症肾病组及健康对照组间上述指标的比较采用方差分析,组间的两两比较采用LSD-t检验。结果与健康对照组比较,高尿酸血症肾病组和高尿酸血症组高密度脂蛋白降低,总胆固醇、低密度脂蛋白、肌酐、尿素氮、尿酸均明显升高[(1.04±0.28)mmol/L vs(1.11±0.38)mmol/L vs(1.73±0.37)mmol/L;(4.32±1.15)mmol/L vs(5.42±1.04)mmol/L vs(3.35±0.78)mmol/L;(3.08±0.96)mmol/L vs(3.62±0.76)mmol/L vs(2.07±0.64)mmol/L;(65.82±28.37)μmol/L vs(80.97±3.34)μmol/L vs(33.67±8.60)μmol/L;(5.55±1.64)mmol/L vs(5.24±1.70)mmol/L vs(3.87±0.75)mmol/L;(487.13±140.91)μmol/L vs(503.60±52.81)μmol/L vs(192.80±63.06)μmol/L],差异有统计学意义(t=-4.622、-5.162,P均<0.001;t=5.519、2.443,P<0.001、=0.019;t=5.159、3.466,P<0.001、=0.001;t=4.832、3.810,P均<0.001;t=2.524、3.197,P=0.015、0.003;t=9.036、8.557,P均<0.001);与健康对照组比较,高尿酸血症肾病组和高尿酸血症组三酰甘油水平升高[(1.23±0.44)mmol/L vs(2.19±0.61)mmol/L vs(0.85±0.45)mmol/L],仅健康对照组与高尿酸血症组比较,差异具有统计学意义(t=3.786,P<0.001)。与健康对照组和高尿酸血症组比较,高尿酸血症肾病组每高倍视野下尿红细胞明显增多[(31.80±59.42)/HP vs(0.60±0.74)/HP vs(2.13±1.92)/HP],差异有统计学意义(t=1.933、2.033,P=0.014、0.017)。与健康对照组比较,高尿酸血症肾病组和高尿酸血症组炎性因子IL-1β、IL-18表达明显增多[(81.20±17.63)ng/L vs(55.19±16.79)ng/L vs(28.41±14.05)ng/L;(870.67±371.13)ng/L vs(718.16±211.42)ng/L vs(323.35±96.16)ng/L],差异有统计学意义(t=4.519、8.907,P均<0.001;t=4.290、5.947,P均<0.001)。在炎性因子IL-1β方面,高尿酸血症肾病组高于高尿酸血症组,差异具有统计学意义(t=4.387,P<0.001)。结论高尿酸血症肾病组中炎性因子IL-1β与IL-18表达水平显著增加,提示炎性因子参与高尿酸致肾损害的发生发展过程,为研究防治高尿酸血症肾病提供新的理论依据。

Objective To detect plasma levels of IL-1βand IL-18 in patients with urate nephropathy and explore their role in this disease.Methods Male patients were selected as subjects between July 2016 and December 2017 in the Affiliated Baoan Hospital of Shenzhen,Southern Medical University.According to the inclusion and exclusion criteria,the patients were divided into three groups(15 patients each):a hyperuricemia group,a urate nephropathy group,and a control group.Blood biochemical indicators were measured using a biochemical analyzer and urinary biochemical parameters were determined using a urine analyzer.Biochemical indicators included blood lipids(total cholesterol,triacylglycerol,low-density lipoprotein and high-density lipoprotein),renal function(creatinine and urea nitrogen),and uric acid.ELISA was used to detect the levels of IL-1βand IL-18 in plasma.The values are expressed as mean±SD.One-way ANOVA was used to compare the means of multiple groups and LSD-t test was adopted to compare the means between two groups.P-values<0.05 were considered to be significant.Results Compared with the control group,the hyperuricemia group and urate nephropathy group had significantly decreased high density lipoprotein and significantly increased low density lipoprotein,total cholesterol,uric acid,creatinine,and blood urea nitrogen[(1.04±0.28)mmol/L,(1.11±0.38)mmol/L vs(1.73±0.37)mmol/L,t=-4.622,-5.162,P<0.001 for both;(4.32±1.15)mmol/L,(5.42±1.04)mmol/L vs(3.35±0.78)mmol/L,t=5.519,2.443,P<0.001 and P=0.019;(3.08±0.96)mmol/L,(3.62±0.76)mmol/L vs(2.07±0.64)mmol/L,t=5.159,3.466,P<0.001 and P=0.001;(65.82±28.37)μmol/L,(80.97±3.34)μmol/L vs(33.67±8.60)μmol/L,t=4.832,3.810,P<0.001 for both;(5.55±1.64)mmol/L,(5.24±1.70)mmol/L vs(3.87±0.75)mmol/L,t=2.524,3.197,P=0.015 and P=0.003;(487.13±140.91)μmol/L,(503.60±52.81)μmol/L vs(192.80±63.06)μmol/L,t=9.036,8.557,P<0.001 for both].Compared with the control group,the hyperuricemia group and urate nephropathy group had increased total triglycerides[(1.23±0.44)mmol/L vs(2.19±0.61)mmol/L vs(0.85±0.45)mmol/L],and there was a significant difference between the control and hyperuricemia groups(t=3.786,P<0.001).Compared with the control group and hyperuricemia group,the urate nephropathy group had significantly higher urine erythrocyte[(31.80±59.42)/HP vs(0.60±0.74)/HP,(2.13±1.92)/HP,t=1.933,2.033,P=0.014,0.017].Compared with the control group,plasma IL-1βand IL-18 levels were significantly increased in the hyperuricemia group and urate nephropathy group[(81.20±17.63)ng/L,(55.19±16.79)ng/L vs(28.41±14.05)ng/L,t=4.519,8.907,P<0.001 for both;(870.67±371.13)ng/L vs(718.16±211.42)ng/L vs(323.35±96.16)ng/L,t=4.290,5.947,P<0.001 for both].Plasma IL-1βlevel was significantly increased in the urate nephropathy group compared with the hyperuricemia group(t=4.387,P<0.001).Conclusion Plasma levels of IL-1βand IL-18 significantly increase in patients with urate nephropathy,which suggests that inflammatory factors play a vital role in the development of hyperuricemia-induced renal damage.