南方医科大学学报

南方医科大学学报 ›› 2019, Vol. 39 ›› Issue (08): 957-.doi: 10.12122/j.issn.1673-4254.2019.08.13

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川芎嗪促进X射线诱导的骨髓衰竭C57小鼠的骨髓修复

张小敏，高磊，胡潇，陈姗姗，聂玲辉，朱玲玲   

  • 出版日期:2019-08-20 发布日期:2019-08-20

Tetramethylpyrazine promotes bone marrow repair in a C57 mouse model of X-rayinduced immune-mediated bone marrow failure

  • Online:2019-08-20 Published:2019-08-20

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摘要： 目的探究不同剂量X射线和川芎嗪对C57小鼠免疫介导的骨髓衰竭（BMF）的影响。方法将C57小鼠随机分成空白照 组、X射线低剂量组（5.0 Gy）、X射线中剂量组（5.75 Gy）、X射线高剂量组（6.5 Gy）。经0.98 Gy/min X射线全身辐照后，受体小 鼠4 h内尾静脉注射4×106个来自DBA/2小鼠的淋巴细胞，观察14 d后各组小鼠的存活率、外周血三系细胞、骨髓有核细胞、骨 髓病理学。采用5.0 Gy X射线造模后，分为模型对照组、川芎嗪低剂量组（5 mg/mL）、川芎嗪中剂量组（10 mg/mL）、川芎嗪高剂 量组（20 mg/mL），12只/组。川芎嗪干预各组每天分别给与相应剂量盐酸川芎嗪溶液腹腔注射，14 d后观察各组小鼠的BMF情 况。结果与正常对照组小鼠相比，BMF小鼠14 d存活率出现降低，其中X射线高剂量组降低最明显；随着X射线剂量的增加， BMF小鼠外周血三系、骨髓有核细胞出现明显下降，差异具有统计学意义（P<0.05或P<0.001），骨髓病理显示骨髓充血明显、有 核细胞减少。采用5.0 Gy X射线建立骨髓衰竭模型后给予川芎嗪溶液治疗，与模型组相比，川芎嗪高剂量组骨髓有核细胞和红 细胞升高最明显（P<0.01或P<0.001），川芎嗪低剂量组白细胞和血小板明显增加（P<0.05或P<0.01）；并且随着川芎嗪给药浓度 的增加，骨髓病理显示骨髓充血减轻及有核细胞呈现增多趋势，并且骨髓中Fas蛋白降低。结论5.0 Gy X射线辐照有利于免疫 介导的BMF实验研究，川芎嗪可通过调节Fas细胞凋亡等信号来参与BMF小鼠骨髓修复，并进一步拓展了“祛瘀生新”理论。

Abstract: Objective To observe the therapeutic effect of tetramethylpyrazine on immune-mediated bone marrow failure (BMF) induced by different doses of X-ray exposure in C57 mice. Methods C57BL6 mice were randomized into 4 groups, including a blank control group and 3 X-ray exposure groups with X-ray exposure at low (5.0 Gy), moderate (5.75 Gy), and high (6.5 Gy) doses. After total body irradiation with 0.98 Gy/min X-ray. The mice as recipient received injections of 4×106 lymphocytes from DBA/2 mice via the tail vein within 4 h. The survival rate of the recipient mice, peripheral blood cell counts, bone marrow nucleated cell count, and bone marrow pathology were examined at 14 days after the exposure. In the subsequent experiment, C57 mice were exposed to 5.0 Gy X-ray and treated with intraperitoneal injection of tetramethylpyrazine at the low (5 mg/mL), moderate (10 mg/mL), or high (20 mg/mL) doses (12 mice in each group) for 14 consecutive days, and the changes in BMF were observed. Results X-ray exposure, especially at the high dose, resulted in significantly lowered survival rate in the mouse models of BMF at 14 days. As the X-ray dose increased, the mice showed significantly reduced peripheral blood counts of red blood cells, white blood cells, platelets and lowered bone marrow nucleated cell counts with obvious bone marrow congestion and reduction of nucleated cells (P<0.05 or 0.001). In the mice exposed to 5.0 Gy X-ray, tetramethylpyrazine at the high dose most obviously increased bone marrow nucleated cells (P<0.01) and red blood cells (P<0.001), and even at the low dose, tetramethylpyrazine significantly increased the counts of white blood cells (P<0.05) and platelets (P<0.01) following the exposure. Tetramethylpyrazine dose-dependently alleviated bone marrow hyperemia, increased bone marrow nucleated cell counts, and lowered Fas protein expression in the bone marrow. Conclusion X-ray irradiation at 5.0 Gy is suitable for establish mouse models of immune-mediated BMF. Tetramethylpyrazine promotes bone marrow repair by regulating Fas cell apoptosis signals, which further expands the traditional Chinese medicine theory of "removing blood stasis to create new."