关木通致急性肾小管坏死患者肾间质微血管病变的研究

Peritubular capillary injury in Chinese herb guan-mu-tong-induced acute tubular necrosis

目的探讨肾间质微血管病变在关木通致急性肾小管坏死肾间质纤维化中的作用及发生机制。方法取4例关木通致急性肾小管坏死患者(A组)、5例抗生素致急性肾小管坏死患者(B组)、5例非IgA型轻度系膜增生性肾小球肾炎患者(C组)肾活检标本,免疫组化SP法观察肾小管上皮血管内皮生长因子(VEGF)表达及肾小管周围毛细血管(PTC)密度及形态改变,电镜观察微血管内皮细胞和基底膜的结构变化。结果(1)A组PTC数目明显少于B组及C组(P<0.01),并可见管腔扩张变形或缩小、血管壁断裂。(2)A组电镜见PTC内皮细胞肿胀,有胞质空泡、致密颗粒,细胞局部与基底膜分离。基底膜有皱缩及增厚。(3)A组肾小管上皮VEGF表达明显少于B组,但2组VEGF表达均多于C组。(4)A、B组PTC密度与肾小管VEGF表达呈正相关(均r=0.793,P<0.01),与肾小管上皮再生呈正相关(r分别为0.880、0.802,P值均小于0.01)。结论关木通致急性肾小管坏死存在原发性肾间质微血管损伤,肾小管VEGF低表达可能参与了损伤过程。关木通致急性肾小管坏死中的微血管病变可能是肾小管中毒性损伤后修复不良及病变慢性化进展的原因之一。

Objective To explore the role and mechanisms of peritubular capillary (PTC) injury in the progression of Chinese Herb guan-mu-tong(GMT, aristolochiae manshuriensis kom) induced acute tubular necrosis (GMT-ATN). Methods Renal biopsy tissue from 4 cases of GMT-ATN and 5 cases of antibiotic induced ATN (A-ATN) were included in the study. Tubulointerstitial injury was semi-quantitatively assessed. Immunohistochemical SP method was applied to reveal PTC as well as the expression of vascular endothelial growth factor (VEGF). Ultra microstructure of endothelial cells and basement membrane of PTC was detected by electronic microscopy(EM). 5 cases of minor mesangioproliferative non-IgA glomerulonephritis were selected as a control group. Results The density of PTC was decreased significantly in GMT-ATN,as compared with the A-ATN and control group (211.08±56.15 vs 413.54±66.59, 536.62±68.38, P<0.01). Dilated and deformed PTC lumina were noted in GMT-ATN with some endothelial cells and basement membrane partially disrupted. Most endothelial cells were found to be swollen with vacuoles dispersed in the cell plasma. The basement membrane was partially shrunk and thickened. The expression of VEGF in renal tubular epithelial cells (RTEC) was much less in the GMT-ATN than that in (A-ATN) group 2.1(0~3.86)% vs [42.5(31.33~60.25)%, P<0.01], even though it was higher than that in the control group [23.1(18.2~39.5)%, P<0.01]; the expression was correlated with PTC density. Close correlation was also found between RTEC regeneration and PTC density, as well as VEGF expression (r=0.880 and 0.802 respectively, P<0.01). Conclusions PTC was markedly injured in GMT-ATN;this could be one of the cause for the continuously progressing tubulointerstitial damage. The low expression of VEGF in RTEC might contribute to the PTC injury process.