归脾丸对苯中毒小鼠骨髓细胞周期的影响

目的观察归脾丸对苯中毒小鼠骨髓细胞周期的影响，并探讨其造血调控作用的可能机制。方法 72只昆明小鼠随机分为正常对照组、模型组、西药组以及归脾丸大、中、小剂量组，每组12只。将小鼠置于人工模拟高苯浓度环境每天8 h，连续14天，复制苯中毒模型。造模后，归脾丸大、中、小剂量组分别给予归脾丸溶液8、4、2 mg/（kg·d）灌胃；西药组给予利血生1.5 mg/（kg·d）和鲨肝醇5 mg/（kg·d）混悬液灌胃；正常对照组和模型组给予生理盐水灌胃，均每天1次，连续3周。应用流式细胞仪检测小鼠骨髓有核细胞计数及骨髓细胞周期。结果与正常对照组比较，模型组骨髓有核细胞计数明显减少（P<0.05）；与模型组比较，归脾丸大、小剂量组及西药组骨髓有核细胞计数均明显增加（P<0.01）。与正常对照组比较，模型组S期细胞比例和细胞增殖指数（proliferation index， PI）增加，G0/G1期细胞比例下降，差异均有统计学意义（P<0.05）。与模型组比较，归脾丸大剂量组G0/G1期细胞比例下降，G2/M期细胞比例和PI增加，归脾丸中剂量组S期细胞比例下降，差异均有统计学意义（P<0.01，P<0.05）。与西药组比较，归脾丸大剂量组在G2/M期细胞比例和PI增加而在G0/G1期细胞比例下降，差异均有统计学意义（P<0.01）。结论归脾丸可能通过调节苯中毒小鼠骨髓细胞周期的G1或G2期检查点，而使细胞进入细胞增殖周期，加速骨髓G0/G1期细胞向S期细胞、S期细胞向G2/M期细胞的转化，促进骨髓造血细胞增殖，提高外周血象，促进骨髓造血功能的恢复。

英文摘要:

Objective To observe the effects of Guipi Pill （GPP） on bone marrow cell cycle of mice exposed to benzene and to explore its possible mechanisms for regulating hematopoiesis. Methods Seventy two Kunming mice were randomly divided into 6 groups， i.e.， the normal control group， the model group， the Western medicine treatment group， the large， middle， and small dose GPP groups， 12 in each group. The mice were exposed to manually simulated high concentrations of benzene for eight h every day， fourteen successive days， to replicate benzene intoxication model. Mice in the large， middle， and small dose GPP groups were administered with 8， 4， 2 mg/kg GPP per day respectively by gastrogavage. Mice in the Western medicine treatment group were administered with leucogen （at the daily dose of 1.5 mg/kg） and batyl alcohol （at the daily dose of 5 mg/kg） by gastrogavage. Mice in the model group and the normal control group were administered with normal saline by gastrogavage， once daily， for 3 successive weeks. The nucleated bone marrow cell count and the cell cycle of bone marrow cells were detected using flow cytometry. Results Compared with the normal control group， the nucleated bone marrow cell count obviously decreased in the model group （P<0.05）. Compared with the model group， the nucleated bone marrow cell count obviously increased in the large and small dose GPP groups， and the Western medicine treatment group （P<0.01）. Compared with the normal control group， the S phase cell ratio and proliferation index （PI） increased， and the G0/G1 phase cell ratio decreased in the model group， showing statistical difference （P<0.05）. The G0/G1 phase cell ratio decreased， while the G2/M phase cell ratio and PI increased in the large dose GPP group. The S phase cell ratio decreased in the middle dose GPP group， showing statistical difference when compared with the model group （P<0.01， P<0.05）. Compared with the Western medicine treatment group， the G2/M phase cell ratio and PI increased， and the G0/G1 phase cell ratio decreased in the large dose GPP group， showing statistical difference （P<0.01）. Conclusion GPP could promote the recovery of hematopoietic functions of benzene exposed mice by ending off G1 or G2 phase arrest， accelerating G0/G1 S phase and S G2/M phase transition， promoting the proliferation of bone marrow hematopoietic cells， and improving the peripheral hemogram.

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