砷染毒对大鼠红细胞的影响及N-ACys干预研究
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摘要
目的:研究低剂量亚砷酸钠对大鼠红细胞的影响,探讨N-乙酰-L-半胱氨酸(N-Acetyl Cysteine,N-ACys)对其的干预作用,进一步评价砷对红细胞的毒性,为慢性砷中毒机制和防治研究、更好发挥砷剂的治疗作用以及减少毒副作用提供重要的科学依据。方法:选择30只SD大鼠,随机分为三组,每组10只,即对照组(给予普通洁净自来水),染毒组(自由饮用含360μg/L砷水),N-乙酰-L-半胱氨酸(Cysteine,Cys)干预组(饮用含360μg/L砷水,隔天灌胃Cys 20mg/kg体重)。每周称量一次大鼠体重,染毒4周后将其处死。计算各器官脏器系数; SDS-PAGE凝胶电泳分离并分析红细胞膜蛋白; MEK-6318K全自动血细胞分析仪测定红细胞参数;血液流变测试仪测定血流变,流式细胞仪红细胞衰亡率;扫描电镜观察红细形态变化;结果采用SPSS13.0统计软件进行分析。
结果:
1.随着时间的延长,SD大鼠体重均有增加,其中Cys干预组大鼠体重增幅最大,但组间差异没有统计学意义(P>0.05);各器官脏器系数与红细胞参数组间差异亦无统计学意义(P>0.05)。
2.血流变测定指标中,与对照组相比,染毒组全血低切表观粘度、红细胞聚集指数、全血低切还原粘度和全血高切还原粘度明显增高(P<0.05);Cys干预组与染毒组相比,全血低切表观粘度、红细胞聚集指数、全血低切还原粘度和全血高切还原粘度明显下降(P<0.05);全血高切表观粘度和血浆粘度组间无统计学意义(P>0.05)。
3.采用SDS-PAGE分离获得红细胞膜α-血影蛋白(Spectrin-α)、β-血影蛋白(Spectrin-β)、锚蛋白(Ankyrin)、带3蛋白(Band 3)、带4.2蛋白(Band 4.2)和肌动蛋白(Actin),共6种蛋白。染毒组红细胞膜带3蛋白含量显著高于对照组(P<0.05),锚蛋含量明显低于对照组(P<0.05); Cys干预组与染毒组相比,红细胞膜带3蛋白含量降低(P<0.05),锚蛋白含量增高(P<0.05);α-血影蛋白、β-血影蛋白、带4.2蛋白和肌动蛋白各组间均无统计学意义(P>0.05)。
4.与对照组相比,染毒组红细胞衰亡率明显增加(P<0.05);Cys干预组与染毒组相比,干预组红细胞衰亡率显著下降(P>0.05)。
5.红细胞形态电镜观察结果显示:对照组红细胞形态正常,为双凹圆盘形,表面光滑规整、细胞大小均匀;染毒组红细胞边缘不规整,细胞出现刺状或棘状突起;干预组红细胞形态基本恢复正常。结论:低剂量亚砷酸钠对大鼠红细胞参数没有明显影响,但可造成红细胞聚集和血粘度增加进而引起血液流变学改变;低剂量亚砷酸钠可致大鼠红细胞膜蛋白表达异常,表现为带3蛋白增高,锚蛋白减少;低剂量亚砷酸钠可引起大鼠红细胞形态学改变和衰亡;Cys对亚砷酸钠所致红细胞毒性具有一定的干预作用。
Objective: To study the change of parameters of erythrocyte induced by low dose sodium arsenite and analyse the intervention effect of Cysteine on erythrocyte. To evaluate the arsenite toxicity of erythrocyte and to provide the scientific basis for making use of the arsenite’s therapeutical effect and reducing the side effect of arsenite.
Method: 30 female Sprague- Dawley rats (180g-200g) were randomly divided into 3 groups, each group involved 10 rats. Control group drunk by ordinary clean tap water; 360μg/L As treatment group were drunk by 360μg/L sodium arsenite; Intevention group were drunk by 360μg/L sodium arsenite and lavaged with Cysteine qd. The SD rats were weighed every weeks.After 4 weeks, all animals were killed. Calculated the organ coefficient and separated the proteins of erythrocyte membrane by SDS-PAGE. The parameters of red blood cell were measured by the MEK-6318K automated hematology analyzer;The hemorheology was tested by Rheology tester automatic and the erythrocyte apoptosis were measured by flow cytometry (FCM). Analyse the shape of erythrocyte with scanning electron microscope (SEM). The results were analysed by SPSS 13.0.
Result:
1. The weight of SD rats were all increased with the time, which the cys intervention group increased most. Howerver, There were no abnormal differences between the three groups.( P>0.05) ; The organ coefficient were alse no differences between the three groups. (P>0.05)
2. Compared with the control group, all the blood parameter of the exposure group and the Cys intervention group have no abnormal change. (P>0.05)
3. Compared with the control group and the Cys intervention group, the blood viscosity under low shear rate, the red blood aggregation and the blood reduced viscosity of the exposure group were obviously increased (P<0.05); Compared with the control group, the red blood aggregation of Cys intervention group were higher (P<0.05); There were no differences between the groups of blood viscosity under highe shear rate and the blood plasma viscosity.
4.Spectrin-α,Spectrin-β,Ankyrin,Band 3,Band 4.2,and Actin of the erythrocyte membrane were separated by SDS-PAGE. The protein of band-3 in exposure group is higher than the control group and intervention group(P<0.05). The ankyrin in exposure group is lower than the control group and intervention group(P<0.05).The expression of protein band-3 and ankyrin between control group and intervention group were not significant. ( P>0.05).
Conclusion:
Low dose sodium arsenite can cause the protein of band-3 expressed highly and the ankyrin lowly in erythrocyte membrane. The change of erythrocyte parameters were not significant by low dose sodium arsenite while the erythrocyte aggregation and blood viscosity increased which caused the hemorheology changed.Erythrocyte morphous was changed and erythrocyte’s apoptosis increased by low dose sodium arsenite.Cysteine has the intervention effect to the erythrocyte toxicity induced by low dose sodium arsenite.
结果:
1.随着时间的延长,SD大鼠体重均有增加,其中Cys干预组大鼠体重增幅最大,但组间差异没有统计学意义(P>0.05);各器官脏器系数与红细胞参数组间差异亦无统计学意义(P>0.05)。
2.血流变测定指标中,与对照组相比,染毒组全血低切表观粘度、红细胞聚集指数、全血低切还原粘度和全血高切还原粘度明显增高(P<0.05);Cys干预组与染毒组相比,全血低切表观粘度、红细胞聚集指数、全血低切还原粘度和全血高切还原粘度明显下降(P<0.05);全血高切表观粘度和血浆粘度组间无统计学意义(P>0.05)。
3.采用SDS-PAGE分离获得红细胞膜α-血影蛋白(Spectrin-α)、β-血影蛋白(Spectrin-β)、锚蛋白(Ankyrin)、带3蛋白(Band 3)、带4.2蛋白(Band 4.2)和肌动蛋白(Actin),共6种蛋白。染毒组红细胞膜带3蛋白含量显著高于对照组(P<0.05),锚蛋含量明显低于对照组(P<0.05); Cys干预组与染毒组相比,红细胞膜带3蛋白含量降低(P<0.05),锚蛋白含量增高(P<0.05);α-血影蛋白、β-血影蛋白、带4.2蛋白和肌动蛋白各组间均无统计学意义(P>0.05)。
4.与对照组相比,染毒组红细胞衰亡率明显增加(P<0.05);Cys干预组与染毒组相比,干预组红细胞衰亡率显著下降(P>0.05)。
5.红细胞形态电镜观察结果显示:对照组红细胞形态正常,为双凹圆盘形,表面光滑规整、细胞大小均匀;染毒组红细胞边缘不规整,细胞出现刺状或棘状突起;干预组红细胞形态基本恢复正常。结论:低剂量亚砷酸钠对大鼠红细胞参数没有明显影响,但可造成红细胞聚集和血粘度增加进而引起血液流变学改变;低剂量亚砷酸钠可致大鼠红细胞膜蛋白表达异常,表现为带3蛋白增高,锚蛋白减少;低剂量亚砷酸钠可引起大鼠红细胞形态学改变和衰亡;Cys对亚砷酸钠所致红细胞毒性具有一定的干预作用。
Objective: To study the change of parameters of erythrocyte induced by low dose sodium arsenite and analyse the intervention effect of Cysteine on erythrocyte. To evaluate the arsenite toxicity of erythrocyte and to provide the scientific basis for making use of the arsenite’s therapeutical effect and reducing the side effect of arsenite.
Method: 30 female Sprague- Dawley rats (180g-200g) were randomly divided into 3 groups, each group involved 10 rats. Control group drunk by ordinary clean tap water; 360μg/L As treatment group were drunk by 360μg/L sodium arsenite; Intevention group were drunk by 360μg/L sodium arsenite and lavaged with Cysteine qd. The SD rats were weighed every weeks.After 4 weeks, all animals were killed. Calculated the organ coefficient and separated the proteins of erythrocyte membrane by SDS-PAGE. The parameters of red blood cell were measured by the MEK-6318K automated hematology analyzer;The hemorheology was tested by Rheology tester automatic and the erythrocyte apoptosis were measured by flow cytometry (FCM). Analyse the shape of erythrocyte with scanning electron microscope (SEM). The results were analysed by SPSS 13.0.
Result:
1. The weight of SD rats were all increased with the time, which the cys intervention group increased most. Howerver, There were no abnormal differences between the three groups.( P>0.05) ; The organ coefficient were alse no differences between the three groups. (P>0.05)
2. Compared with the control group, all the blood parameter of the exposure group and the Cys intervention group have no abnormal change. (P>0.05)
3. Compared with the control group and the Cys intervention group, the blood viscosity under low shear rate, the red blood aggregation and the blood reduced viscosity of the exposure group were obviously increased (P<0.05); Compared with the control group, the red blood aggregation of Cys intervention group were higher (P<0.05); There were no differences between the groups of blood viscosity under highe shear rate and the blood plasma viscosity.
4.Spectrin-α,Spectrin-β,Ankyrin,Band 3,Band 4.2,and Actin of the erythrocyte membrane were separated by SDS-PAGE. The protein of band-3 in exposure group is higher than the control group and intervention group(P<0.05). The ankyrin in exposure group is lower than the control group and intervention group(P<0.05).The expression of protein band-3 and ankyrin between control group and intervention group were not significant. ( P>0.05).
Conclusion:
Low dose sodium arsenite can cause the protein of band-3 expressed highly and the ankyrin lowly in erythrocyte membrane. The change of erythrocyte parameters were not significant by low dose sodium arsenite while the erythrocyte aggregation and blood viscosity increased which caused the hemorheology changed.Erythrocyte morphous was changed and erythrocyte’s apoptosis increased by low dose sodium arsenite.Cysteine has the intervention effect to the erythrocyte toxicity induced by low dose sodium arsenite.
引文
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[3] Ng JC, Wang JP, Zheng B, Zhai C, Maddalena R, Liu F, Moore MR. Urinary porphyrins as biomarkers for arsenic exposure among susceptible populations in Guizhou province, China [J]. Toxicol Appl Pharmacol, 2005, 206(2):176-184.
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