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系统性红斑狼疮(SLE)是一种慢性的、系统性自身免疫性疾病。大量致病性自身抗体及细胞因子的产生、免疫复合物的沉积、多系统损害为该病的主要特点[1-2]。转化生长因子β(TGF-β)家族包括TGF-β1、TGF-β2和TGF-β3三个密切相关的成员,由血小板、单核细胞/巨噬细胞、T细胞和成纤维细胞分泌。TGF-β1是一种抑制性细胞因子,介导免疫耐受,抑制过度炎症反应。同时,TGF-β1又是纤维胶原合成强大的诱导剂,可促进胶原的合成、分泌、加工和交联,同时TGF-β1还可促进其他基质分子如纤连蛋白、血小板反应蛋白-1等的分泌,在致纤维化过程中发挥重要作用,参与肾脏纤维化及狼疮肾炎(LN)病理[3-4]。针对TGF-β1在自身免疫失衡中的研究不少,但结果有所争议[5]。本研究检测TGF-β1在SLE病人外周血血清的表达,旨在分析其表达是否异常并进一步分析其临床意义。
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SLE合并LN组病人TGF-β1水平低于对照组和无LN组(P < 0.05);低活动组SLE病人TGF-β1水平低于高活动组(P < 0.05)(见表 2)。
分组 n TGF-β1水平 对照组 31 13 143.27±5 559.21 SLE无LN组 32 12 671.98±7 767.39 SLE合并LN组 24 9 382.07±7 558.16* F — 3.24 P — < 0.05 MS组内 — 8 448 944 526.714 q检验:与对照组比较*P < 0.05 表 1 TGF-β1在不同肾脏病变组间水平比较(x±s;pg/mL)
分组 n TGF-β1水平 对照组 31 13 143.27±5 559.21 低活动组 36 9 656.62±6 895.79* 高活动组 20 14 151.73±8 610.00 F — 3.47 P — < 0.05 MS组内 — 8 447 618 709.108 q检验:与对照组比较*P < 0.05 表 2 TGF-β1在不同病情活动分组间水平比较(x±s;pg/mL)
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根据主要症状体征的有无以及主要自身抗体的阳性与否分为阳性组与阴性组,2组病人间TGF-β1的水平比较结果显示,在关节炎受累的病人组中表达较高(P < 0.05),抗U1RNP抗体、抗Sm-D1抗体阳性的病人组中表达较低(P < 0.05),按其他症状分组病人之间的TGF-β1的水平差异均无统计学意义(P>0.05)(见表 3)。
分组 关节炎 肾脏病变 血液系统受累 抗核抗体 抗nucleo抗体 抗ds-DNA抗体 抗组蛋白抗体 抗Sm-D1抗体 抗U1RNP抗体 抗SSA60抗体 抗SSA52抗体 抗SSB抗体 抗Scl70抗体 抗着丝点抗体 抗P0抗体 阳性病人 14 531.19±7 953.88 9 382.07±7 558.16 8 385.79±7 102.27 11 426.78±8 427.06 13 754.51±4 399.53 12 468.50±7 723.76 10 731.77±6 049.50 7 721.93±7 324.27 7 989.33±7 120.39 9 010.22±7 872.57 9 675.81±8 615.69 8 450.39±9 030.97 15 173.14±7 433.60 10 833.72±8 339.85 9 419.91±7 139.34 阴性病人 9 954.35±7 414.93 12 671.98±7 767.39 12 332.90±8 023.78 10 353.20±5 420.00 10 508.17±8 693.03 10 681.64±8 313.75 11 342.72±8 734.77 12 752.45±8 103.02 13 880.56±8 086.54 13 441.48±7 760.51 12 054.39±7 717.40 11 794.93±7 809.33 10 920.25±8 098.88 11 211.47±8 123.91 12 394.92±8 535.41 t 2.04 1.59 1.63 0.33 1.61* 0.76 0.23 2.05 2.65 1.98 0.99 1.13 0.88 0.09 1.28 P < 0.05 > 0.05 > 0.05 > 0.05 > 0.05 > 0.05 > 0.05 < 0.05 < 0.05 > 0.05 > 0.05 > 0.05 > 0.05 > 0.05 > 0.05 表 3 外周血血清TGF-β1分别在不同症状病人组间的比较(x±s;pg/mL)
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观察组病人外周血血清TGF-β1的水平与SLEDAI(r=0.190)、C3(r=-0.028)、ESR(r=-0.080)、C反应蛋白(CRP)(r=0.037)无相关性(P>0.05),与外周血RBC计数呈正相关(r=0.342, P < 0.05),与24 h尿蛋白定量(r=-0.413)、血清IgM(r=-0.312)和天门冬氨酸氨基转移酶(AST)(r=-0.321)的水平呈负相关(P < 0.05)。
系统性红斑狼疮病人外周血血清TGF-β1的表达及临床意义
Expression of TGF-β1 in peripheral blood from patients with systemic lupus erythematosus and its clinical significance
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摘要:
目的通过检测转化生长因子β1(TGF-β1)在系统性红斑狼疮(SLE)病人外周血的表达,分析其与临床资料的相关性。 方法选择56例SLE病人(观察组)和35名健康志愿者(对照组),根据是否合并狼疮肾炎(LN),将56例SLE病人分为合并LN组和无LN组,收集SLE病情活动指数(SLEDAI)等临床资料及实验室检查。采用ELISA方法检测血清TGF-β1,并将检测指标与临床资料及实验室检查指标作相关性分析。 结果SLE合并LN病人TGF-β1水平低于对照组(P < 0.05)。低活动组SLE病人TGF-β1水平低于高活动组SLE病人(P < 0.05)。观察组病人外周血血清在关节炎受累的病人组中表达较高(P < 0.05),抗U1RNP抗体、抗Sm-D1抗体阳性的病人组中表达较低(P < 0.05);TGF-β1的水平与SLEDAI、C3、红细胞沉降率、C反应蛋白无相关性(P>0.05),与外周血RBC计数呈正相关(P < 0.05),与24 h尿蛋白定量、血清IgM、球蛋白和天门冬氨酸氨基转移酶的水平呈负相关(P < 0.05)。 结论TGF-β1具有双向免疫调节的作用,可能参与SLE的肾脏及关节病理。 Abstract:ObjectiveTo examine the status and clinical significance of serum transforming growth factor (TGF)-β1 in peripheral blood from patients with systemic lupus erythematosus (SLE). MethodsA total of 56 SLE patients and 35 healthy individuals were recruited into this study.According to the presence of lupus nephritis (LN), the SLE patients were divided into two groups:those with LN and those without LN.The serum levels of TGF-β1 were measured using ELISA.The associations between these measurements and SLE disease activity index (SLEDAI) or other laboratory parameters were analyzed by correlation analysis. ResultsThe serum TGF-β1 level in the SLE patients with LN was significantly lower than that in the healthy controls (P < 0.05).The serum TGF-β1 level in the SLE patients with lower disease activity was significantly lower than that in patients with higher disease activity (P < 0.05).The serum TGF-β1 level was higher in the patients with arthritis than those without, and was lower in the patients with positive anti-U1RNP or anti-Sm-D1 antibody than those of negative.Correlation analysis showed that the serum TGF-β1 level was not significantly correlated with the SLEDAI score, C3 level, erythrocyte sedimentation rate and C reactive protein (P>0.05), but it was positively correlated with the red blood cell count and negatively correlated with globulin, 24 h urine protein, serum IgM and AST (P < 0.05). ConclusionsTGF-β1 has a two-way immunomodulatory effect and may be involved in the pathology of kidney and joint in SLE patients. -
表 1 TGF-β1在不同肾脏病变组间水平比较(x±s;pg/mL)
分组 n TGF-β1水平 对照组 31 13 143.27±5 559.21 SLE无LN组 32 12 671.98±7 767.39 SLE合并LN组 24 9 382.07±7 558.16* F — 3.24 P — < 0.05 MS组内 — 8 448 944 526.714 q检验:与对照组比较*P < 0.05 表 2 TGF-β1在不同病情活动分组间水平比较(x±s;pg/mL)
分组 n TGF-β1水平 对照组 31 13 143.27±5 559.21 低活动组 36 9 656.62±6 895.79* 高活动组 20 14 151.73±8 610.00 F — 3.47 P — < 0.05 MS组内 — 8 447 618 709.108 q检验:与对照组比较*P < 0.05 表 3 外周血血清TGF-β1分别在不同症状病人组间的比较(x±s;pg/mL)
分组 关节炎 肾脏病变 血液系统受累 抗核抗体 抗nucleo抗体 抗ds-DNA抗体 抗组蛋白抗体 抗Sm-D1抗体 抗U1RNP抗体 抗SSA60抗体 抗SSA52抗体 抗SSB抗体 抗Scl70抗体 抗着丝点抗体 抗P0抗体 阳性病人 14 531.19±7 953.88 9 382.07±7 558.16 8 385.79±7 102.27 11 426.78±8 427.06 13 754.51±4 399.53 12 468.50±7 723.76 10 731.77±6 049.50 7 721.93±7 324.27 7 989.33±7 120.39 9 010.22±7 872.57 9 675.81±8 615.69 8 450.39±9 030.97 15 173.14±7 433.60 10 833.72±8 339.85 9 419.91±7 139.34 阴性病人 9 954.35±7 414.93 12 671.98±7 767.39 12 332.90±8 023.78 10 353.20±5 420.00 10 508.17±8 693.03 10 681.64±8 313.75 11 342.72±8 734.77 12 752.45±8 103.02 13 880.56±8 086.54 13 441.48±7 760.51 12 054.39±7 717.40 11 794.93±7 809.33 10 920.25±8 098.88 11 211.47±8 123.91 12 394.92±8 535.41 t 2.04 1.59 1.63 0.33 1.61* 0.76 0.23 2.05 2.65 1.98 0.99 1.13 0.88 0.09 1.28 P < 0.05 > 0.05 > 0.05 > 0.05 > 0.05 > 0.05 > 0.05 < 0.05 < 0.05 > 0.05 > 0.05 > 0.05 > 0.05 > 0.05 > 0.05 -
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