肥大细胞和干细胞因子在糖尿病肾病患者肾组织中的浸润表达及其意义

Expression and Significance of Mast Cells and Stem Cell Factors in Renal Tissue of Patients with Diabetic Nephropathy

目的:探讨肥大细胞(MC)和干细胞因子(SCF)在糖尿病肾病(DN)患者肾组织中的浸润表达情况及其与肾间质损害和肾功能的关系。方法:选取经皮肾活检病理确诊的糖尿病肾病患者52例,按照肾间质病变严重程度将其分为轻度(n=21)、中度(n=20)和重度(n=11)3组,选取5例因肾脏外伤行肾脏切除患者的正常肾组织作为对照组。免疫组化法检测各组患者肾组织中MC、巨噬细胞的浸润和SCF、TGF-β1的表达,原位杂交技术检测SCF基因的表达,并进行相关性分析。结果:(1)与对照组相比,轻、中、重度病变组肾间质中MC[(11.32±3.69)、(27.58±3.94)、(39.96±5.05)比(0.25±0.16),均P<0.01]、巨噬细胞[(131.39±41.25)、(232.98±33.62)、(314.92±33.76)比(15.14±2.46),均P<0.01]、SCF[(0.222±0.055)、(0.324±0.056)、(0.399±0.067)比(0.037±0.027),均P<0.01]、TGF-β1[(0.112±0.049)、(0.267±0.086)、(0.405±0.085)比(0.038±0.023),均P<0.01]的浸润表达及MC脱颗粒水平[(13.38±4.64)%、(32.15±5.58)%、(52.55±5.64)%比(0.00±0.00)%,均P<0.01]均显著增加,且随着间质损害的加重,上述细胞及因子的浸润表达逐渐增加,轻、中、重3组上述各检测指标两组间比较差异均有统计学意义(均P<0.01)。(2)MC计数与血肌酐、尿NAG、RBP、β2-微球蛋白和肾间质巨噬细胞、TGF-β1的浸润表达呈显著正相关(r=0.729、r=0.799、r=0.786、r=0.681、r=0.889、r=0.906,均P<0.001),与eGFR呈显著负相关(r=-0.665,P<0.001)。SCF蛋白与MC计数、MC脱颗粒百分比、巨噬细胞和TGF-β1的浸润表达也呈显著正相关(r=0.827、r=0.811、r=0.780、r=0.792,均P<0.001)。结论:MC、SCF的浸润表达与DN患者肾间质损害程度密切相关,可能是DN患者肾功能不可逆进展的重要参与者。

Objective:To explore the expression of mast cells(MC)and stem cell factor(SCF)in renal tissue of patients with diabetic nephropathy(DN)and its relationship with renal interstitial damage and renal function.Methods:Fifty-two patients with DN diagnosed pathologically by percutaneous renal biopsy were selected and divided into three groups according to the severity of interstitial lesions:mild(n=21),moderate(n=20),and severe groups(n=11).Normal kidney tissues from 5 patients who underwent nephrectomy due to renal trauma were selected as the control group.The infiltration of MC,macrophages and expressions of SCF protein and TGF-β1 in renal tissues of each group were detected by immunohistochemistry.The expression of SCF mRNA was detected by In situ hybridization.And the correlation between them with renal interstitial damage and renal function was analyzed.Results:(1)Compared with the control group,the infiltration and expression of MC[(11.32±3.69),(27.58±3.94),(39.96±5.05)vs.(0.25±0.16),all P<0.01],macrophages[(131.39±41.25),(232.98±33.62),(314.92±33.76)vs.(15.14±2.46),all P<0.01],SCF[(0.222±0.055),(0.324±0.056),(0.399±0.067)vs.(0.037±0.027),all P<0.01],TGF-β1[(0.112±0.049),(0.267±0.086),(0.405±0.085)vs.(0.038±0.023),all P<0.01]and the degranulation level of MC[(13.38±4.64)%,(32.15±5.58)%,(52.55±5.64)%vs.(0.00±0.00)%,all P<0.01]in renal interstitium of mild,moderate and severe groups were increased with statistically significant differences.As the renal interstitial damage increased,the infiltration and expression of the above cells and factors gradually increased,and there were significant differences of these testing indexes in post hoc multiple comparisons(all P<0.01).(2)The count of MC was positively correlated with serum creatinine,urinary NAG,RBP,β2-microglobulin,the infiltration of macrophages and expression level of TGF-β1 in renal interstitium(r=0.729,r=0.799,r=0.786,r=0.681,r=0.889,r=0.906,all P<0.001),and negatively correlated with eGFR(r=-0.665,P<0.001).The expression level of SCF protein was positively correlated with MC count,MC degranulation percentage,the infiltration of macrophage and expression level of TGF-β1(r=0.827,r=0.811,r=0.780,r=0.792,all P<0.001).Conclusion:The number of mast cells and SCF were closely related to the degree of renal interstitial damage in DN patients,and may be an important participant in the irreversible progression of renal function in patients with DN.