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目的探讨人类药物相关性间质性肾炎(D-IN)和IgA肾病(IgAN)肾小管间质免疫炎症反应特点的异同。方法观察33例D-IN(急性23例,慢性10例)和32例IgAN患者肾活检组织中肾小管间质病变的特点,应用免疫组化法观察T淋巴细胞和单核/巨噬细胞浸润情况,α-平滑肌肌动蛋白(α-SMA)和骨桥蛋白(OPN)的表达,结合临床资料进行相关分析。结果两组患者CD3+的T淋巴细胞和CD68+的单核/巨噬细胞均为肾间质的主要浸润细胞。D-IN组急性病例以CD3+细胞为主(CD3+/CD68+为3.7±1.0),慢性病例以CD68+细胞为主(CD3+/CD68+为0.3±0.1,P<0.05)。IgAN组两种细胞在数量上显著相关(r=0.839,P<0.001),比例不随病变程度加重而变化。IgAN组,CD3+与CD68+细胞的浸润程度均与血肌酐、肾间质纤维化以及α-SMA阳性面积呈正相关(r=0.568,0.612;0.703,0.769;0.597,0.655,P均<0.001)。D-IN组,CD3+/CD68+与肾间质纤维化和α-SMA阳性面积呈负相关(r=-0.587、-0.442,P<0.05)。两组肾小管上皮OPN表达均明显增加并与CD68+细胞数量呈正相关(r=0.7604、0.8547,P<0.001)。结论在IgAN中,T淋巴细胞和单核/巨噬细胞可能共同参与肾小管间质的慢性损伤过程;而在D-IN中,单核/巨噬细胞在肾功能恶化和病情慢性化过程中可能起主导作用。
Objective To investigate the similarities and differences of tubulointerstitial immunoinflammatory reaction between human drug-related interstitial nephritis (D-IN) and IgA nephropathy (IgAN). Methods The renal tubulointerstitial lesions in 33 cases of D-IN (acute 23 cases, chronic 10 cases) and 32 cases of IgAN were observed. The infiltration of T lymphocytes and monocytes / macrophages was observed by immunohistochemistry The expression of α-smooth muscle actin (α-SMA) and osteopontin (OPN) were detected by real-time RT-PCR. Results Both CD3 + T lymphocytes and CD68 + monocytes / macrophages were the major infiltrating cells in the renal interstitium. CD3 + cells were predominant in the D-IN group (CD3 + / CD68 + was 3.7 ± 1.0) and CD68 + cells were predominant in the D-IN group (CD3 + / CD68 + was 0.3 ± 0.1, P <0.05). IgAN group was significantly correlated with the number of the two cells (r = 0.839, P <0.001), the proportion does not change with the severity of the disease. The infiltration of IgAN, CD3 + and CD68 + cells was positively correlated with serum creatinine, interstitial fibrosis and positive area of α-SMA (r = 0.568,0.612; 0.703,0.769; 0.597,0.655, P <0.001). D-IN group, CD3 + / CD68 + negative correlation with the area of renal interstitial fibrosis and α-SMA (r = -0.587, -0.442, P <0.05). The expressions of OPN in renal tubular epithelial cells of both groups were significantly increased and positively correlated with the number of CD68 + cells (r = 0.7604,0.8547, P <0.001). Conclusion T lymphocytes and monocytes / macrophages may participate in the process of chronic injury of tubulointerstitium in IgAN. However, in D-IN, monocytes / macrophages are involved in the process of renal dysfunction and chronic disease May play a leading role.