抗血管紧张素Ⅱ1型受体自身抗体与狼疮肾炎发病风险的分析

Analysis of the correlation between autoantibodies against AT1 receptors and risk of lupus nephritis

目的探讨抗血管紧张素Ⅱ1型受体自身抗体(AT1-AA)与LN患病风险的关系。方法通过分别收集本院36名健康对照、32例LN患者的血清后,ELISA法检测AT1-AA,分析并比较2组间AT1-AA分子表达的吸光度(A)值,并进行血糖、血脂、血清肌酐、CRP的检测;进一步对LN患者血清胱抑素C、ESR以及补体C3、C4、ANA及抗dsDNA抗体等检测,通过肾穿刺活检苏木精-伊红(HE)及过碘酸雪夫(PAS)染色肾小球的结构。采用独立样本t检验、χ2检验、Spearman相关性分析及多元线性与回归进行统计分析。结果LN组血清肌酐和CRP[(103±37)μmol/L、(21±8)mg/L]较健康对照组[(72±22)μmol/L、(7±3)mg/L]明显升高,AT1-AA表达的平均A值在LN组(0.33±0.04)较对照组(0.25±0.06)高,差异均具有统计学意义(P<0.01)。多元线性回归分析后显示AT1-AA的表达与CRP(Beta=0.364,P=0.037)及尿蛋白量(Beta=0.497,P=0.004)呈正相关,与补体C3的水平呈负相关(Beta=-0.276,P=0.05)。同时AT1-AA高表达组肾小球病理结果显示系膜及毛细血管内皮增生、肾小球硬化更显著。结论LN患者中AT1-AA的表达明显增高且与CRP、尿蛋白量及补体C3呈一定的相关性,表明该自身抗体可能参与LN的发病及促进疾病的进展。

Objective To study the correlation between autoantibodies against AT1 receptors (AT1-AAs) and risk of lupus nephritis (LN).Methods Thirty-six normal subjects and 32 patients with LN were selected. The AT1-AAs in sera of donors were detected by enzyme-linked immuno sorbent assay (ELISA). The level of AT1-AAs, C-reactive protein (CRP), serum creatinine, lipids and serum glucose in different groups were observed. We tested the serum cystatin c, erythrocyte sedimentation rate (ESR), complement C3, C4, antinuclear antibodies (ANA) and anti-dsDNA antibodies in LN patients. The structures of the glomeruli were stained by renal biopsy hematoxylin-eosin staining (HE) and schiff periodic acid shiff (PAS) . Statistical analysis was performed using independent sample t-test, Chi-square test, Spearman correlation analysis and multiple linear regression.Results Serum creatinine and CRP were significantly higher in the LN group [(103±37) μmol/L, (21±8) mg/L, respectively] than in the control group [(72±22) μmol/L, (7±3) mg/L], all P<0.01. The average A value of AT1-AA was higher in LN patients (0.33±0.04) than in controls (0.25±0.06), P<0.01. Multiple linear regression analysis showed that the expression of AT1-AA was positively correlated with the amount of CRP (Beta=0.364, P=0.037) and urine protein (Beta=0.497, P=0.004), and was negatively correlated with the level of complement C3 (Beta=-0.276, P=0.05). Pathological results showed that mesangial hyperplasia and capillary endothelial proliferation and glomerulosclerosis were more obvious in the AT1-AA positive group than the AT1-AA negative group.Conclusion The expression of AT1-AA is significantly increased in patients with LN and correlated with CRP, urinary protein and complement C3, indicating that the AT1-AA may be involved in the pathogenesis and the progression of LN.