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首页> 中文期刊> 《中国药理学通报》 >注射用丹参多酚酸治疗糖尿病大鼠脑卒中的基因芯片表达谱分析

注射用丹参多酚酸治疗糖尿病大鼠脑卒中的基因芯片表达谱分析

         
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Aim To investigate the effect of salvianolate syophilized injection on brain tissue gene expression profiles in stroke of diabetic rats.Methods T1DM was induced in adult male Wistar rats by injecting streptozotocin.T1DM rats were then subjected to 90 minutes of middle cerebral artery occlusion(MCAO).The rats were randomly assigned to sham group(DM+Sham),ischemia-reperfusion group(DM+ MCAO/R),edaravone group(6 mg·kg-1,ED)and salvianolate lyophilized injection treatment group(5.25,10.5,21 mg·kg-1,SLI)with 13 rats in each group.Drugs were administered by tail vein injection 3 hours after MCAO/R,daily and lasting for 14 days.Infarct volume and gene expression in the brain tissue were detected by TTC staining and the gene chip technique.Results Compared with DM+Sham group,67 differential expressed genes were detected in the DM+MCAO/R group,among which 41 genes were up-regulated and 26 genes were down-regulated.Compared with DM+MCAO/R group,59 differential expressed genes were detected in the SLI(21 mg·kg-1)group,among which 45 genes were up-regulated and 14 genes were down-regulated.Hierarchical cluster results suggested that a number of genes were significantly changed in T1DM rats,such as Ly6i,Pax7 and Irx2.Effects of SLI on the stroke in T1DM rats were majorly related to coagulation and hemostasis system,inflammatory cytokines,oxidative stress,substance metabolism,angiogenesis and signal transduction.Conclusion Salvianolate lyophilized injection protects against focal cerebral ischemia/reperfusion injury in type 1 diabetic rats through regulation of the coagulation and hemostasis system,inflammatory cytokines,oxidative stress,substance metabolism,angiogenesis and signal transduction.%目的 研究注射用丹参多酚酸对糖尿病大鼠脑卒中脑组织基因表达谱的影响.方法 将Wistar大鼠随机分为假手术组(DM+Sham)、糖尿病脑缺血/再灌注损伤模型组(DM+MCAO/R)、依达拉奉组(6 mg·kg-1,ED)、丹参多酚酸治疗组(5.25、10.5、21 mg·kg-1,SLI),每组13只.缺血/再灌注3 h后尾静脉注射给药,每日1次,连续给药14 d.末次给药 30 min后,分别用TTC染色和基因芯片技术检测梗死体积和脑组织中相关基因表达.结果 给药14 d后,与假手术组相比,模型组筛选出67个差异基因,其中41个上调,26个下调;丹参多酚酸(21 mg·kg-1)治疗组与模型组比较差异基因有59个,其中45个上调,14个下调,由聚类分析可得糖尿病局灶性脑缺血/再灌注损伤恢复期有多种基因如Ly6i、Pax7、Irx2发现明显变化,通路分析发现,主要涉及凝血止血、炎症、氧化应激、物质代谢、神经血管新生及信号传导等.结论 丹参多酚酸治疗糖尿病脑卒中主要通过干预凝血止血、炎症、氧化应激、物质代谢、神经血管新生及信号传导等达到治疗目的.

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