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痛风是与高尿酸血症相关,以关节炎反复发作为特点的炎症性疾病。血尿酸过饱后形成的尿酸盐晶体(MSU)是痛风发病的主要致病信号[1]。MSU可以激活细胞膜上Toll样受体(TLR)和细胞内NOD样受体蛋白3(NLRP3)炎性小体诱导IL-1β分泌[2]。IL-1β被认为是启动炎症反应、诱导痛风发病的主要细胞因子。作为模式识别受体,除了MSU外,体内许多代谢性物质(如胆固醇、脂肪酸、ATP等)均可以活化NLRP3炎症小体,引起炎症反应[3]。鉴于NLRP3炎症小体在痛风发病机制中的重要作用以及胆固醇、三酰甘油对NLRP3炎症小体激活作用,提示胆固醇、三酰甘油参与了痛风的发病机制。由于血脂的致炎作用较弱,不会直接引起痛风发病,但能够降低痛风发病的阈值,推测血脂升高可以增加痛风发病的频率。为验证这一假设,本研究拟通过队列研究,探讨胆固醇、三酰甘油水平升高对痛风发病频率的影响。
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本研究所有病例均来自中国科学技术大学附属第一医院(安徽省立医院)的风湿免疫科门诊。入选标准:男性、年龄≥18岁,在医院门诊有血脂检查、依从性良好的痛风病人,所有病人均符合1990年ACR痛风诊断标准。排除标准:慢性痛风迁延不愈;需要服用秋水仙碱、糖皮质激素或非甾体类抗炎药物;合并有感染或者其他炎症性疾病的痛风病人;存在其他自身免疫性疾病;存在慢性消耗性疾病,如恶性肿瘤;肾功能不全;存在显著肝功能异常的病人[(丙氨酸氨基转移酶(ALT)和/或天门冬氨酸氨基转移酶(AST)超过正常值2倍]。本研究获得我院生物医学伦理委员会批准(批准文号为2019KY伦审第73号),在入组时对所有研究对象进行健康饮食宣教并签署知情同意书。
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填写调查问卷,收集病人年龄、痛风病程、血尿酸水平及实验室指标。主要包括(1)一般信息:姓名、性别、年龄、病程、身高、体质量、体质量指数(BMI)、血压、住址、联系电话等;(2)疾病情况:痛风病史(发病时间、发作部位、持续时间等),日常饮食作息及运动情况,痛风发作的时诱因(饮食、运动、受凉、劳累、降尿酸治疗等),有无痛风石,有无肾功能不全,有无其他慢性疾病;(3)治疗情况:是否服用预防痛风发作药物、降尿酸治疗药物、非甾体类抗炎药、激素或其他药物;(4)实验室指标:血常规、红细胞沉降率、C反应蛋白、血糖、肝肾功能、总胆固醇及三酰甘油水平;(5)随访情况:从入组后开始计算,电话随访并记录所有研究对象在1、3、6及12个月痛风发病次数。
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入组病人根据血脂水平分为胆固醇和三酰甘油均正常组(A组)56例、单纯胆固醇升高组(空腹静脉血浆值≥6.2 mmol/L)(B组)21例、单纯三酰甘油升高组(空腹静脉血浆值≥2.26 mmol/L)(C组)50例及胆固醇和三酰甘油均升高组(D组)31例。各组病人年龄、病程、血尿酸水平、身高、体质量、BMI、肌酐、尿素氮、ALT、AST及血糖水平差异均无统计学意义(P>0.05)(见表 1)。电话随访入组病人,记录1、3、6及12个月内的痛风发病次数。分析胆固醇和/或三酰甘油升高对痛风发病频率的影响。由于年龄、BMI、病程、尿酸水平或血糖水平的差异均可造成痛风发病风险改变。为减少这些混杂因素影响,在总样本中按照年龄、BMI、病程、尿酸和血糖水平进行1∶ 1配对,比较胆固醇和/或三酰甘油升高对痛风发病频率的影响。
分组 n 年龄/岁 病程/年 身高/m 体质量/kg BMI/(kg/m2) 尿酸/(μmol/L) 肌酐/(μmol/L) 尿素氮/(μmol/L) ALT/(IU/L) AST/(IU/L) 血糖/(mmol/L) A组 56 48.98±15.12 4.38±4.30 1.73±0.43 74.21±8.48 24.77±2.66 470.66±120.05 77.05±14.05 5.29±1.61 26.64±12.27 25.78±9.31 5.31±0.58 B组 21 48.38±14.91 4.90±3.65 1.73±0.05 73.76±7.98 24.55±2.01 507.05±125.60 83.81±14.41 5.53±1.56 27.48±11.26 23.86±7.13 5.41±1.01 C组 50 45.74±12.63 4.76±4.69 1.73±0.05 79.48±8.84 26.51±2.29 498.59±124.33 77.28±15.91 5.20±1.53 34.65±15.87 27.57±9.47 5.43±0.77 D组 31 41.55±13.74 4.06±3.53 1.74±0.47 78.19±9.04 25.71±2.34 486.18±148.38 79.16±20.57 5.56±1.66 43.06±19.35 27.90±8.00 5.34±0.65 F — 2.02 0.76 0.01 4.4 5.83 0.61 1.02 0.45 9.17 1.25 0.28 P — >0.05 >0.05 >0.05 < 0.01 < 0.01 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 MS组内 — 198.059 19.453 0.110 74.757 5.786 164.031 260.449 2.522 223.304 78.557 0.524 表 1 各组病人一般资料比较(x±s)
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采用t检验、方差分析和q检验。
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与A组比较,B组、C组、D组1、3、6及12个月的痛风发病频率均增加(P < 0.05)。随着时间的延长,4组不同时间段痛风发病频率增加(P < 0.05)(见表 2)。
分组 n 1个月 3个月 6个月 12个月 F P MS组内 A组 56 0.179±0.387 0.393±0.562 0.679±0.664 1.321±0.834 34.52 < 0.01 0.400 B组 21 0.476±0.602* 1.523±0.750* 2.524±1.504* 4.333±2.781* 20.73 < 0.01 2.730 C组 50 0.300±0.463 1.040±0.880*# 1.740±1.275*# 2.900±2.073*# 35.40 < 0.01 1.727 D组 31 0.412±0.502 1.355±1.050* 2.387±1.647*▲ 4.000±2.569*▲ 27.35 < 0.01 2.667 F — 2.84 15.33 19.08 18.48 — — — P — < 0.05 < 0.01 < 0.01 < 0.01 — — — MS组内 — 0.218 0.647 1.496 3.905 — — — q检验:与A组比较*P < 0.05;与B组比较#P < 0.05;与C组比较▲P < 0.05 表 2 各组病人不同时间段痛风发病频率的比较(x±s)
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为减少混杂因素影响,在A组和B组中,按照年龄、BMI、病程、尿酸和血糖水平进行1∶ 1配对,共筛选出14对,记为A1组、B1组。2组1个月内痛风发病频率差异无统计学意义(P>0.05),B1组3、6、12个月痛风发病频率均明显高于A1组(P < 0.01)(见表 3)。
分组 n 1个月 3个月 6个月 12个月 A1组 14 0.214±0.426 0.429±0.646 0.714±0.726 1.143±0.864 B1组 14 0.500±0.650 1.571±0.756 2.429±1.453 4.143±2.878 t — 1.38 3.39 3.63 3.74 P — >0.05 < 0.01 < 0.01 < 0.01 表 3 A1组、B1组不同时间段痛风发病频率比较(x±s)
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为减少混杂因素影响,在A组和C组中,按照年龄、BMI、病程、尿酸和血糖水平进行1∶ 1配对,共筛选出28对,记为A2组、C2组。2组1个月痛风发病频率差异无统计学意义(P>0.05),C2组3、6、12个月痛风发病频率均高于A2组(P < 0.05~P < 0.01)(见表 4)。
分组 n 1个月 3个月 6个月 12个月 A2组 28 0.143±0.356 0.464±0.637 0.679±0.670 1.357±0.559 C2组 28 0.286±0.460 0.929±0.813 1.679±1.389 2.786±2.132 t — 1.29 2.27 3.16 3.41 P — >0.05 < 0.05 < 0.01 < 0.01 表 4 A2组、C2组不同时间段痛风发病频率比较(x±s)
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为减少混杂因素影响,在A组和D组中,按照年龄、BMI、病程、尿酸和血糖水平进行1:1配对,共筛选出13对,记为A3、D3组。2组1个月痛风发病频率差异无统计学意义(P>0.05),D3组3、6、12个月痛风发病频率均明显高于A3组(P < 0.01)(见表 5)。
分组 n 1个月 3个月 6个月 12个月 A3组 28 0.000±0.000 0.308±0.480 0.539±0.519 1.231±0.725 D3组 28 0.231±0.439 1.154±1.144 2.000±1.528 3.308±2.136 t — 1.81 2.46 3.38 2.89 P — >0.05 < 0.05 < 0.01 < 0.01 表 5 A3组、D3组不同时间段痛风发病频率比较(x±s)
胆固醇/三酰甘油水平升高对痛风发病频率的影响
Effect of elevated cholesterol and triglyceride levels on frequency of gout attacks
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摘要:
目的探讨血脂水平升高对痛风发病频率的影响。 方法选取痛风病人158例,根据血脂水平分为胆固醇和三酰甘油均正常组(A组)56例、单纯胆固醇升高组(B组)21例、单纯三酰甘油升高组(C组)50例及胆固醇和三酰甘油均升高组(D组)31例。采用队列研究比较不同血脂水平病人痛风发病频率。 结果与A组比较,B组、C组、D组1个月、3个月、6个月及12个月内痛风发病频率均增加(P < 0.05);随着时间的延长,4组不同时间段痛风发病频率增加(P < 0.05)。按年龄、体质量指数、病程、尿酸和血糖水平进行配对,结果显示,A组与B组共配对14对,记为A1组、B1组,B1组3、6、12个月痛风发病频率均明显高于A1组(P < 0.01);A组与C组共配对28对,记为A2组、C2组,C2组3、6、12个月痛风发病频率均高于A2组(P < 0.05~P < 0.01);A组与D组共配对13对,记为A3、D3组,D3组3、6、12个月痛风发病频率均明显高于A3组(P < 0.01)。 结论血脂水平升高可以增加痛风发病频率。 Abstract:ObjectiveTo investigate the effect of elevated blood lipid levels on the frequency of gout attacks. MethodsA total of 158 gout patients were selected and divided into normal cholesterol and triglyceride group (group A, n=56), simple elevated cholesterol group (group B, n=21), simple elevated triglyceride group (group C, n=50) and elevated cholesterol and triglyceride group (group D, n=31) according to the blood lipid levels. A cohort study was conducted to compare the frequency of gout attacks in patients with different blood lipid levels. ResultsCompared with the group A, the frequency of gout attacks in the group B, group C and group D increased at 1, 3, 6 and 12 months (P < 0.05), and with the extension of time, the frequency of gout attacks in the four groups increased at different time periods (P < 0.05). The patients were paired according to age, body mass index, course of disease, uric acid and blood glucose level, and the results showed that group A and group B were paired with 14 pairs, which were recorded as group A1 and group B1, the frequency of gout attacks in the group B1 was significantly higher than that in the group A1 within 3, 6 and 12 months (P < 0.01);group A and group C were paired with 28 pairs, which were recorded as group A2 and group C2, the frequency of gout attacks in the group C2 was higher than that in the group A2 within 3, 6 and 12 months (P < 0.05 to P < 0.01);group A and group D were paired with 13 pairs, which were recorded as group A3 and group D3, the frequency of gout attacks in the group D3 was significantly higher than that in the group A3 within 3, 6 and 12 months (P < 0.01). ConclusionsElevated blood lipid level can increase the frequency of gout attacks. -
Key words:
- gout /
- cholesterol /
- triglyceride /
- attack frequency
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表 1 各组病人一般资料比较(x±s)
分组 n 年龄/岁 病程/年 身高/m 体质量/kg BMI/(kg/m2) 尿酸/(μmol/L) 肌酐/(μmol/L) 尿素氮/(μmol/L) ALT/(IU/L) AST/(IU/L) 血糖/(mmol/L) A组 56 48.98±15.12 4.38±4.30 1.73±0.43 74.21±8.48 24.77±2.66 470.66±120.05 77.05±14.05 5.29±1.61 26.64±12.27 25.78±9.31 5.31±0.58 B组 21 48.38±14.91 4.90±3.65 1.73±0.05 73.76±7.98 24.55±2.01 507.05±125.60 83.81±14.41 5.53±1.56 27.48±11.26 23.86±7.13 5.41±1.01 C组 50 45.74±12.63 4.76±4.69 1.73±0.05 79.48±8.84 26.51±2.29 498.59±124.33 77.28±15.91 5.20±1.53 34.65±15.87 27.57±9.47 5.43±0.77 D组 31 41.55±13.74 4.06±3.53 1.74±0.47 78.19±9.04 25.71±2.34 486.18±148.38 79.16±20.57 5.56±1.66 43.06±19.35 27.90±8.00 5.34±0.65 F — 2.02 0.76 0.01 4.4 5.83 0.61 1.02 0.45 9.17 1.25 0.28 P — >0.05 >0.05 >0.05 < 0.01 < 0.01 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 MS组内 — 198.059 19.453 0.110 74.757 5.786 164.031 260.449 2.522 223.304 78.557 0.524 表 2 各组病人不同时间段痛风发病频率的比较(x±s)
分组 n 1个月 3个月 6个月 12个月 F P MS组内 A组 56 0.179±0.387 0.393±0.562 0.679±0.664 1.321±0.834 34.52 < 0.01 0.400 B组 21 0.476±0.602* 1.523±0.750* 2.524±1.504* 4.333±2.781* 20.73 < 0.01 2.730 C组 50 0.300±0.463 1.040±0.880*# 1.740±1.275*# 2.900±2.073*# 35.40 < 0.01 1.727 D组 31 0.412±0.502 1.355±1.050* 2.387±1.647*▲ 4.000±2.569*▲ 27.35 < 0.01 2.667 F — 2.84 15.33 19.08 18.48 — — — P — < 0.05 < 0.01 < 0.01 < 0.01 — — — MS组内 — 0.218 0.647 1.496 3.905 — — — q检验:与A组比较*P < 0.05;与B组比较#P < 0.05;与C组比较▲P < 0.05 表 3 A1组、B1组不同时间段痛风发病频率比较(x±s)
分组 n 1个月 3个月 6个月 12个月 A1组 14 0.214±0.426 0.429±0.646 0.714±0.726 1.143±0.864 B1组 14 0.500±0.650 1.571±0.756 2.429±1.453 4.143±2.878 t — 1.38 3.39 3.63 3.74 P — >0.05 < 0.01 < 0.01 < 0.01 表 4 A2组、C2组不同时间段痛风发病频率比较(x±s)
分组 n 1个月 3个月 6个月 12个月 A2组 28 0.143±0.356 0.464±0.637 0.679±0.670 1.357±0.559 C2组 28 0.286±0.460 0.929±0.813 1.679±1.389 2.786±2.132 t — 1.29 2.27 3.16 3.41 P — >0.05 < 0.05 < 0.01 < 0.01 表 5 A3组、D3组不同时间段痛风发病频率比较(x±s)
分组 n 1个月 3个月 6个月 12个月 A3组 28 0.000±0.000 0.308±0.480 0.539±0.519 1.231±0.725 D3组 28 0.231±0.439 1.154±1.144 2.000±1.528 3.308±2.136 t — 1.81 2.46 3.38 2.89 P — >0.05 < 0.05 < 0.01 < 0.01 -
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