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环孢素A,庆大霉素和硒制剂对大鼠外周血淋巴细胞分子和基因表达的影响

Effects of cyclosporine A,gentamycin and selenium preparation on the expressions of molecules and genes from peripheral lymphocytes in rats

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【作者】 王盛宇黄益民顾云张颖赵颂军

【Author】 WANG Sheng-yu,HUANG Yi-min,GU Yun,ZHANG Ying,ZHAO Song-jun (Beijing Institute of Heart Lung and Blood Vessel Disease,Beijing 100029,China)

【机构】 北京市心肺血管疾病研究所北京市心肺血管疾病研究所 北京100029北京100029北京100029

【摘要】 目的 为比较环孢素A ,庆大霉素和硒制剂对细胞免疫功能的不同影响 ,本实验观察了大鼠短期服用环孢素A ,庆大霉素和硒制剂后外周血多种淋巴细胞分子和基因的表达水平变化 ,并对 3组药物进行了对比。方法 将 2 4只大鼠分为 4组 ,分别ig给药。于第 3天取血并分离淋巴细胞。用荧光单克隆抗体 (mAb)标记淋巴细胞分子并提取淋巴细胞总RNA。流式细胞仪检测淋巴细胞分子MHC Ⅱ ,CD4,CD8,ICAM Ⅰ和IL2 R的表达水平 ,基因差异显示分析法检测多基因表达水平。免疫组化法检测各组心肌组织中CD4+,CD8+淋巴细胞数。结果 与对照组相比 ,环孢素A ,庆大霉素和硒制剂都抑制淋巴细胞分子ICAM I,CD4和CD8的表达 ,同时 3组心肌组织中CD4+和CD8+淋巴细胞数降低 ,心肌组织中CD4+淋巴细胞数与CD4分子表达水平明显正相关 (P <0 .0 0 0 1)。 3组的细胞分子表达和心肌淋巴细胞数的降低程度依次为环孢素A >庆大霉素 >硒制剂。不同的是 ,环孢素A还负调MHC Ⅱ和IL2 R的表达水平 ,而庆大霉素却正调MHC II和IL2 R的表达 ,硒制剂负调MHC Ⅱ ,正调IL2 R的表达。 3组都表现出对凋亡基因 gig18和一个 45 0bp左右的待测基因的正调表达。 结论 ①短期服用环孢素A ,庆大霉素和硒制剂 ,都抑制大鼠外周血淋巴细胞对ICAM I ,CD4和CD8等细胞

【Abstract】 OBJECTIVE To investigate the acute effect of cyclosporine A,gentamycin and selenium preparation on the expressions of molecules and genes from peripheral lymphocytes in rats.METHODS 24 normal wistar rats were divided into control and 3 experimental groups.The experimental groups were orally administered with cyclosporine A (CsA),gentamycin and selenium preparation for two days respectively.The peripheral Lymphocytes were isolated and reacted with mono-clone antibodies for labeling molecules of MHC-II,ICAM-I,CD4,CD8 and IL-2R total mRNA in Lymphocyte were extracted.The expressions of molecules and genes were separately evaluated by flow-cytometer and differential display technology.The CD4 + and CD8 + lymphocytes in the myocardium were counted by immuno-histochemistry.RESULTS Compared with the control group,the expressions of CD4,CD8 and ICAM-1 in three experimental groups were all down-regulated,and accompanied with decreased myocardial infiltrations of CD4 + and CD8 + lymphocytes.CD4 + lymphocyte infiltration was significantly correlated with CD4 molecules expression (P<0.0001).The reductions of the molecules and lymphocyte infiltrations in experimental groups trended to CsA>gentamycin>Selenium.In contrast down-regulating expressions of MHC-Ⅱ and IL-2R in CsA group,gentamycin group exhibited to up-regulate MHC-Ⅱ and IL-2R,and selenium preparation group displayed to down-regulate MHC-Ⅱ and up-regulate IL-2R.An apoptosis gene-gig18 mRNA was up-regulated.CONCLUSION ①Short-term administration of CsA,gentamycin and selenium preparation inhibited peripheral lymphocyte expressing CD4,CD8 and ICAM-1 by gradualness.②Three experimental groups appeared different regulating mechanism in MHC-Ⅱ and IL-2R expressions.③An apoptosis gene-gig18 mRNA was up-regulated in all experimental groups.

【关键词】 环孢素A庆大霉素硒制剂基因表达
【Key words】 cyclosporinegentamycinselenium preparationgeneexpression
【基金】 北京市科委心血管病研究实验室支持项目 ( 95 385 0 70 0 );首都医学发展科研基金 (重点学科 )资助项目(ZB199814 )
  • 【文献出处】 中国药学杂志 ,Chinese Pharmaceutical Journal , 编辑部邮箱 ,2003年03期
  • 【分类号】R965
  • 【被引频次】7
  • 【下载频次】86
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