摘要
目的 探讨左旋四氢巴马汀 (L -tetrahydropalmatine ,L -THP)抗脑缺血再灌注损伤的作用机制。方法 采用四血管阻塞法建立大鼠全脑缺血再灌注模型。将 75只Wistar大鼠随机均等地分为 3组 :假手术组 (A组 )、缺血再灌注组 (B组 )、L -THP治疗组 (C组 ) ,在再灌注 2、 6、 12、 2 4和 4 8h时断头取脑选取海马CA1区组织 ,用免疫组化法检测核因子 -κB (NF -κB)、抑制蛋白 -κB (IκB) ,用原位杂交法检测肿瘤坏死因子 -αmRNA (TNF -αmRNA)、白细胞介素 - 1βmRNA (IL - 1βmRNA) ,用苏木精 -伊红 (HE)染色检测存活神经元数目。观察左旋四氢巴马汀对上述 5因子的影响。结果 B组NF -κB、TNF -αmRNA、IL - 1βmRNA的表达显著增加 (P均 <0 0 1) ,IκB和存活神经元数目显著减少 (P均 <0 0 5或 <0 0 1) ;C组NF -κB、TNF -αmRNA、IL - 1βmRNA的表达显著降低(P均 <0 0 1或 <0 0 5 ) ,IκB和存活神经元数目显著增加 (P均 <0 0 1或 <0 0 5 )。结论 全脑缺血再灌注时 ,L -THP可通过抑制IκB的降解和NF -κB的活性 ,下调TNF -αmRNA和IL - 1βmRNA的表达 ,抑制炎症反应 ,提高存活神经元数目 ,起到抗脑缺血再灌注损伤的作用。
Objective To explore the protective effects of L-Tetrahydropalmation (L-THP) on the inflammatory injury in rats after global cerebral ischemia/reperfusion.Methods The global cerebral ischemia/reperfusion models were established by four- vessel occlusion method.Wistar rats were randomly divided into three groups:sham operation group (group A,n=25),ischemia/reperfusion group (group B,n=25),L-THP group(group C,n=25),the rats were separately decapitated at 2h?6h?12h?24h and 48h.The expressions of NF-κB and IκB in hippocampus CA 1 field were measured by immunohistochemical method,the expressions of TNF-αmRNA and IL-1βmRNA were detected by in situ hybridization method.The number of the surviving neurons was examined by HE stain.Results The expressions of NF-κB,TNF-αmRNA and IL-1βmRNA in B group increased significantly (P<0 01),the expression of IκB and the number of the surviving neurons decreased(P<0 01 or P<0 05).But the levels of NF-κB,TNF-αmRNA and IL-1βmRNA in C group were lower than that in B group (P<0 05 or P<0 01),the expression of IκB and the number of the surviving neurons in C group was higher(P<0 05 or P<0 01).Conclusion The experiment shows that L-THP could protect the brain from global cerebral ischemia/reperfusion injury,and the mechanism might be related to its increasing the expression of IκB and decreasing the activation of NF-κB and reducing the expressions of TNF-αmRNA and IL-1βmRNA.
出处
《中国全科医学》
CAS
CSCD
2004年第10期713-715,共3页
Chinese General Practice
基金
湖北省科技厅 2 0 0 3年湖北省科技攻关计划 [编号2 0 0 3AA30 1C51 ]
关键词
左旋四氢巴马汀
脑缺血再灌注损伤
作用机制
治疗
L-tetrahydropalmatine Global cerebral ischemia/reperfusion Nuclear factor-κB Inhibitory protein-κB Tumor necrosis factor-αmRNA Interleukin-1βmRNA