C3a和C5a在局灶性节段性肾小球硬化症中的作用

目的研究C3a、C5a在局灶性节段性肾小球硬化症(FSGS)患者中的作用。方法(1)选取经肾活检证实的FSGS患者共66例,其中顶端型18例,门部型11例,非特殊型22例,细胞型10例,塌陷型5例;选取10例肾脏肿瘤患者手术切除的正常肾组织作阴性对照。采用免疫组化方法检测肾组织C3a、C5a的表达。(2)收集这66例FSGS患者的血清及尿液标本,以同期体检中心的10例健康成人的血清及尿液标本作为正常对照。采用酶联免疫吸附法(ELISA)检测血清及尿液中的C3a、C5a水平。结果(1)免疫组化结果显示,C3a、C5a在FSGS患者肾小球中沉积,在正常肾组织未见沉积。半定量评分结果显示,FSGS患者肾脏C3a沉积评分与血肌酐(r=0.547,P<0.001)及24 h尿蛋白量(r=0.329,P=0.007)呈正相关,肾脏C5a沉积评分与血肌酐(r=0.415,P<0.001)及24 h尿蛋白量(r=0.414,P<0.001)亦呈正相关。(2)FSGS患者血清C3a、C5a水平高于健康成人(均P<0.05),但各型之间差异无统计学意义(P>0.05)。FSGS患者尿C3a/尿肌酐、尿C5a/尿肌酐水平高于健康成人(均P<0.05),塌陷型尿C3a/尿肌酐、尿C5a/尿肌酐水平高于其他型FSGS(均P<0.01),但顶端型、门部型、非特殊型、细胞型之间差异无统计学意义(P>0.05)。(3)FSGS患者尿C3a/尿肌酐水平与血肌酐(r=0.774,P<0.001)及24 h尿蛋白量(r=0.430,P<0.001)呈正相关,尿C5a/尿肌酐水平亦与血肌酐(r=0.677,P<0.001)及24 h尿蛋白量(r=0.333,P=0.007)呈正相关。结论补体C3a、C5a可能参与FSGS发病,并可能与疾病的严重程度相关。

Role of C3a and C5a in focal segmental glomerulosclerosis

Objective To study the role of C3a and C5a in focal segmental glomerulosclerosis (FSGS) patients. Methods (1) A total of 66 patients with FSGS confirmed by renal biopsy were selected, including 18 cases of tip lesion, 11 cases of perihilar, 22 cases of not otherwise specified (NOS), 10 cases of cellular, and 5 cases of collapsing FSGS. The normal renal tissue resected from patients with kidney tumor was taken as a negative control. The expression of C3a and C5a in renal tissues was detected by immunohistochemistry. (2) Serum and urine samples from these 66 FSGS patients were collected, and serum and urine samples from 10 healthy adult selected from the same physical examination center in the same term were used as normal controls. The levels of C3a and C5a in serum and urine were detected by enzyme-linked immunosorbent assay (ELISA). Results (1) Immunohistochemical results showed that C3a and C5a were deposited in glomerulus of FSGS patients, and no deposition in normal renal tissues. The semi-quantitative score showed that kidney C3a score was significantly correlated with serum creatinine (r=0.547, P＜0.001) and 24 h urine protein (r=0.329, P=0.007) in FSGS patients, and kidney C5a score was also significantly correlated with serum creatinine (r=0.415, P＜0.001) and 24 h urine protein (r=0.414, P＜0.001) in FSGS patients. (2) The levels of serum C3a and C5a in FSGS patients were higher than those in healthy adults (both P＜0.05), but there was no significant difference among the five pathological types (P＞0.05). The levels of urinary C3a/urinary creatinine, urinary C5a/urinary creatinine were higher in FSGS patients than those in healthy adults (all P＜0.05). The levels of urine C3a/urinary creatinine and urinary C5a/urinary creatinine in collapsing FSGS were higher than other FSGS types (all P＜0.01), but there was no significant difference among the tip lesion, the perihilar, the not otherwise specified and the cellular (P＞0.05). (3) Urinary C3a/urinary creatinine levels were significantly correlated with serum creatinine (r=0.774, P＜0.001) and 24 h urine protein (r=0.430, P＜0.001) in FSGS patients, and urinary C5a/urinary creatinine levels were also significantly correlated with serum creatinine (r=0.677, P＜0.001) and 24 h urine protein (r=0.333, P=0.007) in FSGS patients. Conclusion Complement C3a and C5a may be involved in the pathogenesis of FSGS and may be related to the severity of FSGS.