| 引用本文: | 李剑锋，刘明义，田卫斌，王胜春*，王俊琴.乐尔脉对脑缺血再灌注损伤大鼠海马组织炎性反应的影响[J].中国现代应用药学,2009,(9):703-708. |
| LI Jianfeng, LIU Mingyi, TIAN Weibin, WANG Shengchun*, WANG Junqin.Effect of Le Er Mai on the Inflammatory Response in Hippocampial Tissue of Cerebral Ischemia Reperfusion Injuried Rats[J].Chin J Mod Appl Pharm(中国现代应用药学),2009,(9):703-708. |
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| 摘要: |
| 目的研究乐尔脉对大鼠脑缺血再灌注损伤海马组织炎性反应的作用。方法采用大鼠大脑中动脉阻断(middle cerebral artery occlusion，MCAO)造成局灶性脑缺血2 h再灌注3 d模型，采用干燥法测定脑含水量和TTC染色法测定脑梗死面积，化学法与I-125放免法测定海马组织中MDA、LD、TNF-α、IL-6含量，RT-PCR测定海马组织中COX-2、MCP-1、MMP-2、9、13 mRNA的表达，Western blot检测海马组织P38与NF-κB信号通路蛋白的表达。结果乐而脉与氟桂利嗪可明显减轻脑水肿和梗死面积，降低海马组织中IL-6、TNF-α、MDA和LD含量(P<0.05)，海马组织中MCP-1、COX-2、MMP-2、13mRNA的表达下调(P<0.05)。Western blot 测定结果显示乐尔脉和氟桂利嗪组明显降低海马组织P38MAPK和P-P38MAPK表达(P<0.05)，同时也降低NF-κB65、P-NF-κB65、C-fos表达，增加C-jun与IκB表达(P<0.05), 氟桂利嗪降低NF-κB65但不降低p-NF-κB65表达。结论脑缺血再灌注诱导海马组织细胞释放的细胞因子和介质活化P38MAPK与NF-κB/IκB信号转导通路级联反应，MCP-1、COX-2mRNA和MMP-2、9、13mRNA转录增加，IL-6、TNF-α、MDA、LD生成增多，导致脑水肿和脑梗死面积扩大，乐尔脉抑制脑缺血再灌注诱导海马组织细胞释放炎症介质的作用可能与降低p38MAPK和NF-κB /IκB信号通路活化作用有关。 |
| 关键词: 脑缺血再灌注 乐尔脉 炎性因子 核转录因子 基质金属蛋白酶 |
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| Effect of Le Er Mai on the Inflammatory Response in Hippocampial Tissue of Cerebral Ischemia Reperfusion Injuried Rats |
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LI Jianfeng, LIU Mingyi, TIAN Weibin, WANG Shengchun*, WANG Junqin
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| Abstract: |
| OBJECTIVE To study the effects of Le Er Mai(LEM) on inflammatory response in hippocampial tissue of cerebral ischemia reperfusion (CIR) in rats. METHODS A CIR injuried model was produced using middle cerebralartery occlusion (MCAO) . The rat brain containing water was detected by drying test, and the cerebral infarct area was measureed by 2,3,5-triphenlytetrazolium chloride (TTC). The chemistry method and I-125 radio-immunity method were employed to determine the content of MDA, lactate (LD), tumor necrosis factor (TNF-α) and interneuckin-6 (IL-6) in hippocampus tissue. The expression of minocyte chermoattractant protein-1mRNA (MCP-1 mRNA), cyclooxygenase-2mRNA,(COX-2 mRNA), and matrix metalloproteinase-2,3,9 mRNA(MMP-2,9,13 mRNA) were examined by RT-PCR.The expression of mitogen activated protein kinase (P38MAPK), phosphorylation mitogen activated protein kinase (P-P38MAPK), nuclear factor-kappa-κB (NF-κB), phosphorylation nuclear factor-kappaB (P-NF-κB), inhibitory-κB (IκB), phosphorylation inhibitory-κB (P-IκB) and transcription factor (c-fos, c-jun ) were detected by Western blod. RESULTS Ler Er Mai and Flunarizinum alleviated the brain edemal and brain infarct area in cerebral ischemia reperfusion rats, and the contents of IL-6, TNF-α, MDA and LD were markedly decreased in hippocampus tissue. The expressions of P-38MAPK and P-38MAPK in hippocampus of CIR rats were augmented in compared with sham-operated rats, and the brain tissue containing water and CIR infarct area were significantly increased. The apoptosis rate of hippocampus neuronal in CIR model were increased, and blood brain barrier were impaired. Besides, the expression of MMP-2, MMP-13, MCP-1, COX-2 mRNA were upregulated in ischemia 2h after reperfusion 3d in rats model group. In compared with CIR model group, LEM and Flunarizinum treatment groups, the expression of MMP-2,13mRNA were downregulated and neuronal apoptosis was attenuated. CONCLUSION Cytokine and medium were released in hippocampus induced by cerebral ischemia reperfusion activating p38MAPK and NF-κB/IκB signaling transcription pathway cascades reaction. Mcp-1, COX-2, and MMP-2,9,13mRNA transcription were increased, IL-6, TNF-α, MDA, LD synthesis were augmented, conducing brain edema and brain infarct area amplification. The effect of LEM on inhibition of the hippocampus tissue cell liberating inflammatory medium induced by CIR may be related to inhibitetion the activation of p38MAPKand NF-κB/IκB signaling pathway. |
| Key words: brain ischemia reperfusion (CIR) Le Er Mai (LEM) inflammation nuclear factor-kappaB (NF-κB) matrix metalloproteinase (MMP) |
