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目的研究慢性马兜铃酸肾病(CAAN)管周毛细血管(PTC)的损害特点以及PTC损害引起的低氧对CAAN进展的影响。方法将54只Wistar大鼠随机分为2组关木通组(30只)大鼠予关木通水煎剂灌胃连续用药8周,在第8、12、16周分别处死10只大鼠;对照组(24只)大鼠予饮用水灌胃,连续8周,在第8、12、16周分别处死8只大鼠。留取血、尿、肾组织标本分别作生化、病理、免疫组织化学、免疫印迹等检查。结果关木通组大鼠从第8周开始,肾功能逐渐恶化、尿蛋白增加,PTC损害加重,PTC密度减少,血管内皮生长因子(VEGF)表达逐渐减少,但低氧诱导因子1α(HIF-1α)表达逐渐增加。第16周时两组比较(1)对照组HIF-1α-IOD值为(0·49±0·06)×103,关木通组HIF-1α-IOD值为(7·11±1·20)×103(P<0·01);(2)对照组PTC密度为(42·80±4·49)/0·13mm2,关木通组PTC密度为(8·10±2·28)/0·13mm2(P<0·01);(3)对照组VEGF-IOD值为(26·94±9·34)×103,关木通组VEGF-IOD值为(2·78±0·78)×103(P<0·01)。肾间质面积第8周较对照组减小,第12周开始逐渐增大,第16周明显增大。结论CAAN大鼠存在严重的PTC损害和低氧,缺血、缺氧与CAAN的进展有关。
Objective To investigate the characteristics of peritubular capillaries (PTC) in chronic aristolochic acid nephropathy (CAAN) and the effects of hypoxemia induced by PTC on the progression of CAAN. Methods Fifty-four Wistar rats were randomly divided into 2 groups (30 rats). The rats were treated with Guanmutong decoction orally for 8 weeks, and 10 rats were sacrificed on the 8th, 12th and 16th week respectively. The control group 24) rats were given drinking water for 8 weeks, respectively, at the 8th, 12th and 16th weeks, 8 rats were sacrificed. Blood, urine and kidney tissue samples were taken for biochemical, pathological, immunohistochemical, immunoblot and other tests. Results The rats in Guanmutong group started to deteriorate their renal function, increased urinary protein, increased the damage of PTC, reduced the density of PTC and decreased the expression of vascular endothelial growth factor (VEGF), but the expression of hypoxia inducible factor 1α (HIF-1α) Expression gradually increased. At the 16th week, the HIF-1α-IOD value in the control group was (0.49 ± 0.06) × 103 and the HIF-1α-IOD in the Guanmutong group was (7.1 ± 1.20) × (P <0.01); (2) In the control group, the PTC density was (42.80 ± 4.49) /0.13 mm2 and that in the Guanmutong group was (8.10 ± 2.28) /0.13 mm2 P <0.01). (3) The VEGF-IOD of the control group was (26.94 ± 9.34) × 103 and the VEGF-IOD of the Guanmutong group was (2.78 ± 0.78) × 103 (P < 0 · 01). Compared with the control group, the area of renal interstitium reduced in the 8th week, and gradually increased from the 12th week to the 16th week. Conclusion CAAN rats have severe PTC damage and hypoxia, ischemia, hypoxia and the progress of CAAN.