川芎嗪对免疫介导骨髓衰竭小鼠肾脏氧化应激的影响

Effect of tetramethylpyrazine on renal oxidative stress in immune-mediated bone marrow failure mice

目的 探讨川芎嗪(tetramethylpyrazine,TMP)对免疫介导的骨髓衰竭(BMF)小鼠肾脏氧化应激的影响。方法 将C57小鼠随机分成正常对照组、单纯辐照组(TBI)、模型组、TMP低剂量组(5 g·L -1 )、TMP中剂量组(10 g·L -1 )、TMP高剂量组(20 g·L -1 )。C57小鼠经5.0 Gy X射线全身辐照和淋巴细胞输注,建立BMF模型。观察14 d后小鼠外周血三系细胞、骨髓有核细胞、骨髓病理学、肾脏病理学及氧化应激等指标。结果 模型组骨髓病理显示有核细胞减少,外周血三系明显降低,说明成功建立免疫介导BMF模型;模型组肾脏病理显示肾小管水肿,氧化应激指标MDA升高,抗氧化应激指标GSH、SOD、GSH-Px下降,提示BMF小鼠肾脏存在氧化应激损伤。经TMP治疗后,肾脏病理未见明显异常,肾脏中MDA下降及GSH、SOD上升,免疫组化结果显示,HIF-1α表达下降,并出现VEGF表达。结论 TMP可减轻免疫介导的BMF小鼠肾脏氧化应激损伤,可能与调节HIF-1α/VEGF表达有关。

Aim To explore the effects of tetramethylpyrazine (TMP) on renal oxidative stress in immune-mediated bone marrow failure (BMF) C57 mice. Methods C57 mice were randomly divided into normal control group, total body irradiation group (TBI), model group, TMP low dose group (5 g·L -1 ), TMP medium dose group (10 g·L -1 ), and TMP high dose group (20 g·L -1 ). The BMF model was established by total body irradiation with 5.0 Gy X-ray and lymphocyte infusion. The peripheral blood triline cells, bone marrow nucleated cells, bone marrow pathology, kidney pathology and oxidative stress indexes were observed 14 days later. Results Bone marrow pathology of the model group showed that the bone marrow nucleated cells decreased and the peripheral blood triline cells decreased significantly, indicating that the immune-mediated BMF model was successfully established. Renal pathology of model group showed tubular edema, and the oxidative stress index MDA increased, and the antioxidant stress indicators GSH, SOD, GSH-Px decreased, indicating that there was renal oxidative stress damage in BMF mice. After treatment with TMP, there was no obvious abnormality in renal pathology, the oxidative stress index MDA of the kidney decreased and the antioxidant stress index GSH, SOD increased. Immunohistochemistry showed that the expression of HIF-1α decreased and VEGF existence was observed. Conclusions TMP can alleviate renal oxidative stress injury in immune-mediated BMF mice, which may be related to the regulation of HIF-1α/VEGF expression.