慢性马兜铃酸肾病大鼠模型的早期贫血机制探讨

目的 探讨慢性马兜铃酸肾病(CAAN)大鼠模型的早期贫血机制。方法 将78只Wistar雌性大鼠随机分为3组:(1)关木通组(n=30):予关木通水煎剂灌胃连续用药8周；(2)正常对照组(n=24):予饮用水灌胃，连续用药8周；(3)5/6肾切除组(n=24):自由饮水。在第8、12、16周分别随机处死各组大鼠总数的1/3，留取尿、血和骨髓组织标本，分别作生化、ELISA、HE染色、免疫组化、电镜、红细胞生成素(EPO)定量等检查。结果 关木通组大鼠和5/6肾切除组大鼠BUN和Scr从第8周开始升高，但关木通组大鼠肾功能损伤进展迅速。关木通组大鼠第12周开始出现贫血，第16周贫血加重，与正常对照组和5/6肾切除组相比，P < 0.01。关木通组大鼠早期血清和骨髓组织TNF-α和IL-1β表达明显增多，与正常对照组和5/6肾切除组相比，P<0.01。随着病情进展血窦内皮损伤加重，骨髓组织CD34表达、微血管密度MVD和造血组织面积逐渐下降，与正常对照组和5/6肾切除组相比差异有统计学意义，P < 0.01。各组大鼠血清EPO定量比较，差异没有统计学意义。 结论 CAAN大鼠模型血清和骨髓组织早期TNF-α和IL-1β表达明显增多，骨髓微血管损伤可能是其贫血发生早且较严重的原因。

Mechanism of early anemia in rat model of chronic aristolochic acid nephropathy

Objective To investigate the mechanism of early anemia in rat model of chronic aristolochic acid nephropathy(CAAN). Methods Seventy-eight female Wistar rats were randomly divided into three groups. Group A(n=30) were treated with caulis aristolochiae manshuriensis(CAM) decoction for 8 weeks. Group B (n=24) were treated with drinking water for 8 weeks. Group C were 5/6 nephrectomized rats (n=24). At week 8， 12 and 16， 1/3 rats in each group were sacrificed respectively. Before the rats were sacrificed， specimens of blood， urine and bone marrow were taken for biochemistry， ELISA， pathology， immunohistochemical analysis and the quantitation of erythropoietin (EPO). Results BUN and Scr of group A and group C increased at week 8， but the renal function of group C deteriorated quickly. Group A presented anaemia at week 12， and became worse at week 16. Hemoglobin (Hb) level of group A was lower as compared with group B and group C，P < 0.01. Compared with group B and group C， the TNF-α and IL-1β in blood serum and myeloid tissue of group A increased significantly(P < 0.01)， along with the decrease of CD34 expression and MVD. EPO level of each group was normal. Conclusion The expression of TNF-α and IL-1β increases at the early phase of CAAN， and the microvessel of bone marrow is markedly injured， which may result in early onset of severe anemia in rat CAAN model.