狼疮肾炎中医风湿内扰证候与血Fractalkine及尿血管细胞黏附分子-1的相关性研究
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摘要
目的:通过分析狼疮肾炎患者血Fractalkine(FKN)以及尿血管细胞黏附分子-1(vascular cellular adhesion molecule-1,VCAM-1)的水平及实验室常用指标与中医风湿内扰证候之间的关系。方法:对确诊为66例狼疮肾炎患者进行辨证分型分为风湿内扰组36例及非风湿内扰组30例。另选取健康体检的正常人20例作为对照组,收集临床资料及实验室指标并同步留取血、尿标本,ELISA法检测86例标本血Fractalkine与尿VCAM-1水平,综合分析风湿内扰证候与上述指标之间的关系。结果:(1)风湿内扰组患者较非风湿内扰组易出现发热乏力(45.8%VS 19.2%)、关节炎(29.2%VS 3.8%)、高血压(35.9%VS 7.7%)、浮肿(41.7%VS 0%)(P<0.05);(2)风湿内扰组患者血Fractalkine(1.78±1.19 VS 0.94±0.83)及尿VCAM-1(62.37±27.65 VS 27.21±30.14)水平均显著高于非风湿内扰组(P<0.01);血红蛋白定量(113.29±29.21 VS 127.04±12.32)、血白蛋白定量(34.77±6.92 VS 43.33±3.08)均低于非风湿内扰组(P<0.05);风湿内扰组24 h尿蛋白定量水平(2170.01±1469.30 VS 278.25±178.86)、尿红细胞定量(10.00(0.75,20.00)VS 0.00(0.00,0.75))均高于非风湿内扰组,(P<0.01);风湿内扰组中血C3水平低于非风湿内扰组,ANA滴度、anti-dsDNA及anti-SM阳性率明显高于非风湿内扰组(P<0.05);风湿内扰组SLEDAI积分、BILAG积分均高于非风湿内扰组(P<0.01);(3)风湿内扰证候与血Fractalkine、尿VCAM-1、尿红细胞、24 h尿蛋白、SLEDAI积分、BILAG积分、ANA滴度呈正相关(P<0.01),与血白蛋白呈负相关(P<0.01)。(4)风湿内扰组病理类型以IV型及IV+V型为主。结论:狼疮肾炎风湿内扰证候与疾病活动度密切相关,当临床出现风湿内扰证时需警惕狼疮肾炎疾病的活动。
Objective:The aim was to explore the correlation between the levels of serum Fractalkine,urine Vascular cellular adhesion molecule-1(VCAM-1) and common laboratory activityindicators in lupus nephritis(LN) patients with the endorheumatism syndrome in LN. At the same time,to provide objective standard for the micro differentiation and clinical evaluation of treatments for traditional Chineses medicine syndromes. Methods:Totally 68 LN patients and 20 healthy volunteers were enrolled in this study. Sixty-eight LN patients were assigned to endorheumatism group(36 cases) and non-endorheumatism group(30 cases). Twenty healthy volunteers were taken as the normal control group. Clinical data, serum and urine samples were collected from all enrollers. The levels of serum Fractalkine and urine VCAM-1 were detected by ELISA. Result:(1)Patients in the endorheumatism group compared with the group of non-endorheumatism were more prone to get fever(37.5% VS 7.7%), fatigue(45.8% VS 19.2%), arthritis(29.2% VS 3.8%), hypertension(35.9% VS 7.7%), edema(41.7% VS 0%)(P<0.05).(2)The endorheumatism group's levels of serum Fractalkine[(1.78±1.19) VS(0.94±0.83)] and uVCAM-1 [(62.37±27.65)VS(27.21±30.14)] were statistically significant higher than those of the group of non-endorheumatism group(P<0.01). The levels of hemoglobin[(113.29±29.21) VS(127.04±12.32)] and serum albumin[(34.77±6.92) VS(43.33±3.08)] were lower than those of the non-endorheumatism group, which constituted a statistically significant difference(P>0.05), especially the serum albumin levels(P<0.01). The 24-hour urinary protein levels [(2 170.01±1 469.30) VS(278.25±178.86)], uRBC levels[(10.00(0.75,20.00) VS 0.00(0.00,0.75)] in the endorheumatism group were higher than that of the non-endorheumatism group. There were statistically significant differences(P<0.01). The ANA titers, anti-SM and anti-dsDNA positive rate in the endorheumatism group was statistically significantly higher than that of the non-endorheumatism group,but serum C3 levels was lower(P<0.05). The scores of SLEDAI in the endorheumatism group were higher than that of the non-endorheumatism group,which constituted a statistically significant differences(P<0.01).(3)The Endorheumatism syndrome was positively correlated with the levels of serum Fractalkine,uVCAM-1,uRBC and 24-hour proteinuria as well as the scores of SLEDAI and BILAG, and it was also positively correlated with the ANA titers(P<0.01), while negatively correlated with the levels of serum albumin(P<0.01).(4)The mainly pathological type in the endorheumatism group was type IV and IV+V. Conclusion:Among patients with lupus nephritis, the endorheumatism syndrome is closely related to the disease activity. We need to guard against the disease activity,when the endorheumatism syndrome appears in clinic.
Objective:The aim was to explore the correlation between the levels of serum Fractalkine,urine Vascular cellular adhesion molecule-1(VCAM-1) and common laboratory activityindicators in lupus nephritis(LN) patients with the endorheumatism syndrome in LN. At the same time,to provide objective standard for the micro differentiation and clinical evaluation of treatments for traditional Chineses medicine syndromes. Methods:Totally 68 LN patients and 20 healthy volunteers were enrolled in this study. Sixty-eight LN patients were assigned to endorheumatism group(36 cases) and non-endorheumatism group(30 cases). Twenty healthy volunteers were taken as the normal control group. Clinical data, serum and urine samples were collected from all enrollers. The levels of serum Fractalkine and urine VCAM-1 were detected by ELISA. Result:(1)Patients in the endorheumatism group compared with the group of non-endorheumatism were more prone to get fever(37.5% VS 7.7%), fatigue(45.8% VS 19.2%), arthritis(29.2% VS 3.8%), hypertension(35.9% VS 7.7%), edema(41.7% VS 0%)(P<0.05).(2)The endorheumatism group's levels of serum Fractalkine[(1.78±1.19) VS(0.94±0.83)] and uVCAM-1 [(62.37±27.65)VS(27.21±30.14)] were statistically significant higher than those of the group of non-endorheumatism group(P<0.01). The levels of hemoglobin[(113.29±29.21) VS(127.04±12.32)] and serum albumin[(34.77±6.92) VS(43.33±3.08)] were lower than those of the non-endorheumatism group, which constituted a statistically significant difference(P>0.05), especially the serum albumin levels(P<0.01). The 24-hour urinary protein levels [(2 170.01±1 469.30) VS(278.25±178.86)], uRBC levels[(10.00(0.75,20.00) VS 0.00(0.00,0.75)] in the endorheumatism group were higher than that of the non-endorheumatism group. There were statistically significant differences(P<0.01). The ANA titers, anti-SM and anti-dsDNA positive rate in the endorheumatism group was statistically significantly higher than that of the non-endorheumatism group,but serum C3 levels was lower(P<0.05). The scores of SLEDAI in the endorheumatism group were higher than that of the non-endorheumatism group,which constituted a statistically significant differences(P<0.01).(3)The Endorheumatism syndrome was positively correlated with the levels of serum Fractalkine,uVCAM-1,uRBC and 24-hour proteinuria as well as the scores of SLEDAI and BILAG, and it was also positively correlated with the ANA titers(P<0.01), while negatively correlated with the levels of serum albumin(P<0.01).(4)The mainly pathological type in the endorheumatism group was type IV and IV+V. Conclusion:Among patients with lupus nephritis, the endorheumatism syndrome is closely related to the disease activity. We need to guard against the disease activity,when the endorheumatism syndrome appears in clinic.
引文
[1] Wang Z,Li M,Wang Y,et al.Long-term mortality and morbidity of patients with systemic lupus erythematosus: a single-center cohort study in China[J].Lupus,2018,27(5):864-869.
[2] Peng L,Wang Z,Li M,et al.Flares in Chinese systemic lupus erythematosus patients: a 6-year follow-up study[J].Clin Rheumatol, 2017,36(12):2727-2732.
[3] 温成平,谢志军,尤晓娟,等.中医药对狼疮肾炎激素不同使用阶段的治疗策略研究[J].中华中医药学刊,2011,29(4):680-682.
[4] 王庆苗.名中医治疗狼疮性肾炎的文献理论研究[J].中国中医药现代远程教育,2014,12(9):3-4.
[5] 中华中医药学会肾病分会.狼疮肾炎的诊断、辨证分型及疗效评定(试行方案)[J].上海中医药杂志,2008,42(2):9-10.
[6] Petri M,Magder L.Classification criteria for systemic lupus erythematosus: a review[J]. Lupus, 2004, 13:829-837.
[7] Isenberg DA,Rahman A,Allen E,et al.BILAG 2004. Development and initial validation of an updated version of the British Isles Lupus Assessment Group’s disease activity index for patients withsystemic lupus erythematosus[J].Rheumatology(Oxford),2005,44(7):902-906.
[8] 柯凌.叶任高教授治疗狼疮性肾炎的思路与经验[J].中国中西医结合肾病杂志,2001,2(4):190-191.
[9] 盛梅笑,王钢.狼疮性肾炎中医病机与治法探讨[J].中国中医基础医学杂志,2003,9(12):55-57.
[10] 黄玉茵. 狼疮性肾炎的中医治[C]. 2008年全国中西医结合肾脏病南京论坛论文汇编,2008:272-273.
[11] 严小倩,鲁盈,林京莲.狼疮肾炎中医风湿证候与活动性指标的相关性研究[J].中国中西医结合杂志,2015,35(20):147-149.
[12] Bazan JF,Bacon KB,Hardiman G,et al.Anew class of membrane-bound chemokine with a CX3C motif[J]. Nature,1997,385:640-644.
[13] Cockwell P,Chakravorty SJ,Girdlestone J,et al.Fractalkine expression in human renal inflammation[J].J Pathol,2002,196(1):85-90.
[14] Segerer S,Hughes E,Hudkins KL,et al.Expression of the fractalkine receptor(CX3CR1) in human kidney diseases[J].Kidney Int,2002,62(2):488-495.
[15] 唐可京,李幼姬,谢灿茂,等.Fractalkine/CX3CRl在Ⅳ型狼疮肾炎患者肾组织中的表达[J].中国病理生理杂志,2007,23(5):908-912.
[16] 尤燕舞,廖品琥,覃月秋,等.Fractalkine 在狼疮性肾炎患者血液和肾组织中的表达及其意义[J].南方医科大学学报,2013,33(4):520-523.
[17] Yoshimoto S,Nakatani K,Iwano M,et al.Elevated levels of fractalkine expression and accumulatio of CD16+ monocytes in glomeruli of active lupus nephritis[J].Am J Kidney Dis,2007,50(1):47-58.
[18] Sandeep Singh,Tianfu Wu,Chun Xie,et al.Urine VCAM-1 as a marker of renal pathology -activity index in lupus nephritis[J].Arthritis Research &Therapy,2012,14(4):R164.
[19] Ilic T,Mitic I,Durdevic-Mirkovic T,et al.Correlation Betw -een sera levels of sICAM-1 and sVCAM-1 and severity ofkidney lesions in patients with lupus Nephritis[J].Med Pregl,2007,60(Suppl2):128-132.
[20] Skeoch S,Haque S,Pemberton P,et al.Cell adhesion molecules as potential biomarkers of nephritis,damage and accelerated atherosclerosis in patients with SLE[J].Lupus,2014,23(8):819-824.
[21] Kiani AN,Wu T,Fang H,et al.Urinary vascular cell adhesion molecule,but not neutrophil gelatinaseassociated lipocalin,is associated with lupus nephritis[J].J Rheumatol,2012,39(6):1231-1237.
[22] Abd-Elkareem MI,Al Tamimy HM,Khamis OA,et al.Increased urinary levels of the leukocyte adhesion molecules ICAM-1 and VCAM-1 in human lupus nephritis with advanced renal histological changes: preliminary findings[J].Clin Exp Nephrol,2010,14(6):548-557.
[23] 王悦,鲁盈.狼疮肾炎中医风湿证候与肾脏病理活动性病变相关性[J].临床肾脏病杂志,2015,15(6):333-336.
[24] 鲁盈.试论从风湿辨治狼疮性肾炎[J].中国中西医结合肾病杂志, 2010,11(4):286-287.
[25] 蒋炜,黎磊石.狼疮性肾炎中西医结合治疗研究:附196例分析[J].中华肾脏病杂志,1992,8(3):137-140.
[26] 刘正钊,胡伟新,章海涛,等.激素联合雷公藤多苷治疗V型狼疮性肾炎的I临床疗效[J].肾脏病与透析肾移植杂志,2008,17:512-516.
[27] 陈国文.雷公藤多苷联合小剂量泼尼松治疗狼疮肾炎的临床观察[J].中医药导报,2012,18:45-47.
[28] 刘谓, 阎磊, 朱清,等. 雷公藤多苷联合醋酸泼尼松治疗中度活动型系统性红斑狼疮的疗效观察[J].中华实用诊断与治疗杂志,2014,28(12):234-238.
[2] Peng L,Wang Z,Li M,et al.Flares in Chinese systemic lupus erythematosus patients: a 6-year follow-up study[J].Clin Rheumatol, 2017,36(12):2727-2732.
[3] 温成平,谢志军,尤晓娟,等.中医药对狼疮肾炎激素不同使用阶段的治疗策略研究[J].中华中医药学刊,2011,29(4):680-682.
[4] 王庆苗.名中医治疗狼疮性肾炎的文献理论研究[J].中国中医药现代远程教育,2014,12(9):3-4.
[5] 中华中医药学会肾病分会.狼疮肾炎的诊断、辨证分型及疗效评定(试行方案)[J].上海中医药杂志,2008,42(2):9-10.
[6] Petri M,Magder L.Classification criteria for systemic lupus erythematosus: a review[J]. Lupus, 2004, 13:829-837.
[7] Isenberg DA,Rahman A,Allen E,et al.BILAG 2004. Development and initial validation of an updated version of the British Isles Lupus Assessment Group’s disease activity index for patients withsystemic lupus erythematosus[J].Rheumatology(Oxford),2005,44(7):902-906.
[8] 柯凌.叶任高教授治疗狼疮性肾炎的思路与经验[J].中国中西医结合肾病杂志,2001,2(4):190-191.
[9] 盛梅笑,王钢.狼疮性肾炎中医病机与治法探讨[J].中国中医基础医学杂志,2003,9(12):55-57.
[10] 黄玉茵. 狼疮性肾炎的中医治[C]. 2008年全国中西医结合肾脏病南京论坛论文汇编,2008:272-273.
[11] 严小倩,鲁盈,林京莲.狼疮肾炎中医风湿证候与活动性指标的相关性研究[J].中国中西医结合杂志,2015,35(20):147-149.
[12] Bazan JF,Bacon KB,Hardiman G,et al.Anew class of membrane-bound chemokine with a CX3C motif[J]. Nature,1997,385:640-644.
[13] Cockwell P,Chakravorty SJ,Girdlestone J,et al.Fractalkine expression in human renal inflammation[J].J Pathol,2002,196(1):85-90.
[14] Segerer S,Hughes E,Hudkins KL,et al.Expression of the fractalkine receptor(CX3CR1) in human kidney diseases[J].Kidney Int,2002,62(2):488-495.
[15] 唐可京,李幼姬,谢灿茂,等.Fractalkine/CX3CRl在Ⅳ型狼疮肾炎患者肾组织中的表达[J].中国病理生理杂志,2007,23(5):908-912.
[16] 尤燕舞,廖品琥,覃月秋,等.Fractalkine 在狼疮性肾炎患者血液和肾组织中的表达及其意义[J].南方医科大学学报,2013,33(4):520-523.
[17] Yoshimoto S,Nakatani K,Iwano M,et al.Elevated levels of fractalkine expression and accumulatio of CD16+ monocytes in glomeruli of active lupus nephritis[J].Am J Kidney Dis,2007,50(1):47-58.
[18] Sandeep Singh,Tianfu Wu,Chun Xie,et al.Urine VCAM-1 as a marker of renal pathology -activity index in lupus nephritis[J].Arthritis Research &Therapy,2012,14(4):R164.
[19] Ilic T,Mitic I,Durdevic-Mirkovic T,et al.Correlation Betw -een sera levels of sICAM-1 and sVCAM-1 and severity ofkidney lesions in patients with lupus Nephritis[J].Med Pregl,2007,60(Suppl2):128-132.
[20] Skeoch S,Haque S,Pemberton P,et al.Cell adhesion molecules as potential biomarkers of nephritis,damage and accelerated atherosclerosis in patients with SLE[J].Lupus,2014,23(8):819-824.
[21] Kiani AN,Wu T,Fang H,et al.Urinary vascular cell adhesion molecule,but not neutrophil gelatinaseassociated lipocalin,is associated with lupus nephritis[J].J Rheumatol,2012,39(6):1231-1237.
[22] Abd-Elkareem MI,Al Tamimy HM,Khamis OA,et al.Increased urinary levels of the leukocyte adhesion molecules ICAM-1 and VCAM-1 in human lupus nephritis with advanced renal histological changes: preliminary findings[J].Clin Exp Nephrol,2010,14(6):548-557.
[23] 王悦,鲁盈.狼疮肾炎中医风湿证候与肾脏病理活动性病变相关性[J].临床肾脏病杂志,2015,15(6):333-336.
[24] 鲁盈.试论从风湿辨治狼疮性肾炎[J].中国中西医结合肾病杂志, 2010,11(4):286-287.
[25] 蒋炜,黎磊石.狼疮性肾炎中西医结合治疗研究:附196例分析[J].中华肾脏病杂志,1992,8(3):137-140.
[26] 刘正钊,胡伟新,章海涛,等.激素联合雷公藤多苷治疗V型狼疮性肾炎的I临床疗效[J].肾脏病与透析肾移植杂志,2008,17:512-516.
[27] 陈国文.雷公藤多苷联合小剂量泼尼松治疗狼疮肾炎的临床观察[J].中医药导报,2012,18:45-47.
[28] 刘谓, 阎磊, 朱清,等. 雷公藤多苷联合醋酸泼尼松治疗中度活动型系统性红斑狼疮的疗效观察[J].中华实用诊断与治疗杂志,2014,28(12):234-238.