益髓理血饮减少二甲基苯蒽诱导的骨髓增生异常综合征大鼠骨髓细胞凋亡

Effect of the traditional Chinese medicine compound Yisui Lixue decoction on apoptosis of marrow cells in rats with myelodysplastic syndrome induced by dimethyl benzanthracene

目的:探索中药复方益髓理血饮对二甲基苯蒽诱导的骨髓增生异常综合征(myelodysplastic syndrome,MDS)模型大鼠骨髓细胞凋亡的作用。方法:采用化学诱变剂二甲基苯蒽诱导建立大鼠MDS模型,并分为正常对照组、模型+PBS组、模型+复方皂矾丸组、模型+益髓理血饮低剂量组和模型+益髓理血饮高剂量组,每组12只。于造模第14天开始分组连续给药30 d。观察各组大鼠一般情况,给药后的第31天将各组的大鼠处死,显微镜下观察骨髓细胞的病理学改变,检测各组大鼠外周血细胞、免疫组织化学检测Bcl-2和Bax蛋白表达,流式细胞仪检测骨髓细胞凋亡情况。结果:与正常对照组相比,模型+PBS组大鼠骨髓细胞病态造血,外周白细胞、红细胞、血红蛋白和血小板下降明显,促凋亡蛋白Bax明显增加,抑凋亡蛋白Bcl-2表达明显减少(P<0.01),与模型+PBS组相比,治疗各组大鼠外周白细胞、红细胞、血红蛋白和血小板升高,促凋亡蛋白Bax明显减少,抑凋亡蛋白Bcl-2表达明显增加(P<0.05或P<0.01),尤以模型+益髓理血饮高剂量组最为明显(P<0.01);与正常对照组相比,模型+PBS组骨髓细胞的总凋亡率、早期凋亡率和晚期凋亡率均有所增加(P<0.01),治疗各组的凋亡率均有所下降(P<0.05或0.01),尤其总凋亡率和早期凋亡率下降更为明显,仅有益髓理血饮对降低晚期凋亡率疗效明显(P<0.01),且高剂量组优于低剂量组。结论:中药复方益髓理血饮治疗MDS能改善其外周血细胞情况,降低促凋亡蛋白Bax表达,升高抑凋亡蛋白Bcl-2表达,减少骨髓细胞凋亡。

Objective： To investigate the effect of the traditional Chinese medicine compound Yisui Lixue decoction on apoptosis of marrow cells in rats with myelodysplastic syndrome （MDS） induced by dimethyl benzanthracene （DMBA）. Methods： The rats with MDS induced by the chemical mutagens DMBA were divided into 5 groups （12 rats in each group）： a control group, a model＋PBS group, a model＋compound Zaofan pill group, a model＋low dose ofYisui Lixue decoction group and a model＋high dose ofYisui Lixue decoction group. After DMBA treatment for 14 days, rats were treated with different drugs for 1 month and executed on the 31 day. The peripheral blood cells, expressions orB-cell lymphoma-2 （Bcl-2） and Bcl-2 associated X protein （Bax）, apoptosis of bone marrow cells were measured. Results： The counts of peripheral leukocyte, erythrocyte, hemoglobin and platelet in the model＋PBS group were significantly decreased compared with those in the control group （P〈0.01）, while the peripheral hemograms of the treatment groups were improved significantly compared with those in the model＋PBS group （P〈0.05 or P〈0.01）, especially in the model＋high dose group （P〈0.01）. In the model＋PBS group, the expressions of Bax and Bcl-2 was significantly increased （P〈0.01） or decreased （P〈0.01）, respectively, which were reversed by treatment ofYisui Lixue decoction （P〈0.05 or P〈0.01）, especially in the model＋high dose group （P〈0.01）. Compared with control group, the total apoptosis rate, earlier apoptosis and later apoptosis rate of bone marrow cells in the model＋PBS group were increased （P〈0.01）, which were blocked by treatment ofYisui Lixue decoction （P〈0.0S or P〈0.01）, and the model＋high dose group was better than the model＋low dose group. Conclusion： The traditional Chinese medicine compound Yisui Lixue decoction can improve peripheral hemogram, decrease the expression of Bax, increase the expression of Bcl-2, and reduce the apoptosis of bone marrow cells.