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目的探讨血小板反应因子1(TSP-1)与慢性马兜铃酸肾病(CAAN)肾间质纤维化及肾小管周围毛细血管(PTC)丢失的关系。方法 36只SD大鼠被随机分为CAAN模型组(用关木通浸膏水溶液间断灌胃)及对照组(仅自来水灌胃),每组18只。分别于第4、8和12周处死6 只大鼠,用肾组织切片做免疫组化染色。对TSP-1、转化生长因子-β1(TGF-β1)、氨基肽酶P (APP)、血管内皮生长因子(VEGF)及I型胶原(Col I)的表达进行半定量分析。结果与对照组比较,模型组大鼠肾间质TSP-1、肾小管TGF-β1及肾间质Col I表达均显著上调(P均<0．01)。3 者间表达量呈显著正相关(r=0．925、0．910、0．857,P均<0．01)。模型组大鼠肾间质APP表达明显下调(P<0．01),与TSP-1、Col I表达量呈显著负相关(r=-0．945、-0．883,P均<0．01)。模型组肾小管VEGF表达上调(P<0．01),其表达量与APP呈显著负相关(r=-0．607,P<0．01),而与TGF- β1呈显著正相关(r=0．625,P<0．01)。结论 ISP-1-TGF-β轴表达增强及与TSP-1相关的PTC丢失均可能参与CAAN肾间质纤维化,而VEGF表达上调为代偿表现。
Objective To investigate the relationship between platelet-responsive factor 1 (TSP-1) and renal interstitial fibrosis and peritubular capillaries (PTC) in chronic aristolochic acid nephropathy (CAAN). Methods Thirty-six SD rats were randomly divided into CAAN model group (intermittent gavage with aqueous solution of Guanmutong extract) and control group (tap water only), with 18 rats in each group. Six rats were sacrificed at weeks 4, 8 and 12, respectively, and immunohistochemically stained with kidney tissue. The expression of TSP-1, TGF-β1, APP, VEGF and Col I were semi-quantitatively analyzed. Results Compared with the control group, the expressions of TSP-1, TGF-β1 in renal tubule and Col I in renal interstitium were significantly increased in model group (all P <0.01). There was a significant positive correlation between the three expression levels (r = 0.925,0.910,0.857, P <0.01). The expression of APP in the model group was significantly decreased (P <0.01), and negatively correlated with the expression of TSP-1 and Col I (r = -0.945, -0.883, P <0.05). 01). The expression of VEGF in the model group was up-regulated (P <0.01), and the expression was negatively correlated with APP (r = -0.607, P <0.01), but positively correlated with TGF- = 0.625, P <0.01). Conclusion The increased expression of ISP-1-TGF-β axis and the loss of PTC associated with TSP-1 may be involved in CAAN renal interstitial fibrosis, while the upregulation of VEGF expression is compensatory.