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低分子肝素-超氧化物歧化酶共价结合物对脑缺血再灌注沙土鼠脑组织中TNF-α、IL-1β和IL-6表达的影响

Effects of LMWH-SOD conjugate on the expression of TNF-α,IL-1β and IL-6 in gerbil brain injurred with ischemia/reperfusion

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【作者】 张鸿伟王凤山

【Author】 ZHANG Hong-wei, WANG Feng-shan*(Institute of Biochemical and Biotechnological Drug, School of Pharmaceutical Science, Shandong University, Jinan 250012, China)

【机构】 山东大学药学院生化与生物技术药物研究所

【摘要】 目的研究低分子肝素-超氧化物歧化酶共价结合物(LMWH-SOD)对脑缺血再灌注沙土鼠脑组织中炎性细胞因子TNF-α,IL-1β和IL-6表达的影响。方法将蒙古沙土鼠随机分组,分别给予一定剂量的生理盐水、低分子肝素(Low Molecular weight heparin,LMWH)、超氧化物歧化酶(Superoxide dismutase,SOD)、低分子肝素/超氧化物歧化酶混合物(LMWH+SOD)以及LMWH-SOD,制作脑缺血再灌注模型和假手术组,再灌注6h后取脑组织上清使用ELISA试剂盒进行细胞因子测定。结果运用Oneway ANOVA辅以LSD-t为统计分析方法分析测定结果,显示LMWH-SOD用药组脑组织上清中TNF-α和IL-1β含量显著低于各对照组(P<0.001或0.05),IL-6含量显著低于生理盐水组(P<0.001),但与LMWH组、SOD组以及LMWH+SOD组相比无统计学差异(P>0.05)。结论LMWH-SOD对脑缺血再灌注沙土鼠脑组织中三种炎性细胞因子TNF-α,IL-1β和IL-6的早期表达上调有显著的抑制效应,综合作用效果优于LMWH、SOD及LMWH+SOD。

【Abstract】 OBJECTIVE To study the effects of low molecular weight heparin-superoxide dismutase conjugate (LMWH-SOD) on the expression of TNF-α, IL-1β and IL-6 in gerbil brain injurred with ischemia/reperfusion. METHODS Mongolian gerbils were divided randomly into 5 groups (n=10). Certain amount of normal saline (NS), LMWH, SOD, LMWH+SOD and LMWH-SOD were administered intravenously to corresponding animals. Ischemia/reperfusion operation was performed to every group except the sham-operated group. 6h after reperfusion, the cytokines in brain supernatant were determined by ELISA method. RESULTS The results were processed by oneway ANOVA, followed by post-hoc multiple comparison analysis with Fisher’s least significant difference test. The group treated with LMWH-SOD presented lowest expression level of TNF-α and IL-1β among all groups (P<0.001 or 0.05) and IL-6 expression level was also markedly lower than NS group (P<0.001), but showed no statistical difference compared with group of LMWH, SOD and LMWH+SOD (P>0.05). CONCLUSION Compared with LMWH, SOD and LMWH+SOD, LMWH-SOD showed more comprehensive effects on inhibiting early increasing expression of TNF-α, IL-1β and IL-6.

【基金】 国家自然科学基金资助项目(30270492)
  • 【会议录名称】 2006第六届中国药学会学术年会论文集
  • 【会议名称】2006第六届中国药学会学术年会
  • 【会议时间】2006-11
  • 【会议地点】中国广东广州
  • 【分类号】R965
  • 【主办单位】中国药学会
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