干细胞因子在狼疮肾炎患者肾组织中的表达及意义

目的 探讨干细胞因子(SCF)在狼疮肾炎(LN)患者肾组织中的表达及其与狼疮活动、肾损害有关指标的关系.方法 采用原位杂交和免疫组织化学技术,分别在基因和蛋白质水平检测[34例LN,16例慢性肾小球肾炎(CGN),8名健康对照]肾组织中SCF及其受体c-kit(CD117)的表达,同时检测肥大细胞、巨噬细胞及α-平滑肌肌动蛋白(α-SMA)阳性细胞的浸润情况.计算狼疮肾组织活动指数和慢性指数得分及肾间质损害程度.结果 ①LN及CGN肾组织中SCF的表达及肥大细胞较对照组明显增加(t=6.03～14.25,P<0.01).间质损害程度相似的LN与CGN相比较,肾间质SCF、肥大细胞差异无统计学意义.②SCF与肥大细胞、巨噬细胞、α-SMA及临床指标的相关性:相应部位SCF的表达、α-SMA的表达、肥大细胞、巨噬细胞的浸润数量呈显著正相关(r=0.47～0.86,P<0.01).SCF的表达、α-SMA的表达及巨噬细胞数量与肾病理活动性指数、慢性化指数、肾间质损害程度、尿蛋白定量均呈显著正相关(r=0.34～0.93,P<0.05或0.01),与肌酐清除率(Ccr)呈明显负相关(r=-0.39～0.61,P<0.01).SCF及巨噬细胞与抗dsDNA滴度、补体C3、SLE疾病活动指数(SLEDAI)积分也有显著相关性.肥大细胞数与LN慢性指数特别是肾间质损害程度呈明显正相关(r=0.86,r=0.93,P<0.01)与Ccr呈明显负相关(r=-0.56,P<0.01).与LN活动指标无相关性.结论 SCF在LN肾组织呈广泛表达,其表达量与多种炎症细胞、肾脏固有细胞、肾功能、尿蛋白、疾病活动性及严重程度等密切相关,提示SCF可能是LN病理过程中一个关键的全程参与者.

Expression and significance of stem cell factor in renal tissue of patients with lupus nephritis

Objective To investigate the renal expression of stem cell factor (SCF) in lupus nephritis (LN) and its correlation with disease activity and renal injury parameters. Methods Histochemical stain was used to examine all renal specimens (LN group n=34, chronic glomerulonephritis n=16, control group n=8). Hyhridization in situ and immunohistochemistry were used to detect the expression of SCF and infiltration of mast cells, macrophages , α-SMA (+) cells in renal tissues of the two groups. SPS software was used for tissue of the control group. However, they increased markedly in lupus nephritis and CGN (t=6.03～14.25, P< 0.01). But there was no significant difference between LN and CGN in SCF and mast cells in renal interstitium. Positive correlation was observed among the expression of SCF and α-SMA and the number of mast cells and macrophages (r=0.47～0.84, P<0.01) at their corresponding locations. The expression of SCF and ot-SMA and the number of macruphages were positively correlated with renal pathological active index, chronic index, albuminuria and the injury of renal interstitium (r=0.34～0.93, P<0.05 or 0.01); meanwhile, it was negatively correlated with Ccr(r=-0.39～0.61, P<0.01). There was significant correlation between SCF, macrophages and anti-dsDNA antibody, complement C3 level, SLE disease activity index (SLEDAI). The number of mast cells in renal interstitium was positively correlated with chronic indexes and the injury of renal interstitium (r=-0.86, r=0.93, P<0.01) and negatively correlated with Ccr (r=-0.56, P<0.01), but not correlated with active index and albuminuria (r=0.27, r=0.23, P>0.05). Conclusion The expression of SCF is widespread in kidney, and it is markedly eorrelated with various kinds of inflammatory cells, renal inherent cells, renal function, and urine protein levels. SCF may be an critical participant in the initiation and progression of renal injuries in human lupus nephritis.