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目的:观察吴茱萸次碱(Rut)对局灶性脑缺血(p MCAO)大鼠的保护作用,进一步探讨其对Toll样受体2/4(TLR2/4)和核因子-κB(NF-κB)表达的影响。方法:采用改进的Koizumi方法制备大鼠永久性大脑中动脉阻塞(p MCAO)模型,分为模型组,假手术组和Rut高、中、低剂量组(10,5,1 mg·kg-1)。造模3 d后ip Rut,模型与假手术组ip相应体积的生理盐水,连续给药1周后观察Rut对大鼠脑缺血后脑梗死体积、脑组织含水量的影响。采用蛋白印迹法及免疫组织化学法检测脑组织中TLR2/4和NF-κB的表达;酶联免疫吸附(ELASA)试剂盒检测血清中肿瘤坏死因子-α(TNF-α)和白介素-1β(IL-1β)含量。结果:大鼠局灶性脑缺血后,脑梗死体积和脑组织含水量升高;和假手术组相比,缺血侧TLR2,TLR4,NF-κB的蛋白表达升高,阳性细胞也明显增多;血清中TNF-α和IL-1β含量显著提高(P<0.01)。和模型组相比,Rut可显著减少脑梗死体积和脑组织含水量(P<0.05);Rut干预后TLR2/4-NF-κB信号通路被抑制(P<0.05);血清中TNF-α和IL-1β含量明显降低(P<0.05)。结论:吴茱萸次碱对大鼠局灶性脑缺血损伤有明显的保护作用,其作用机制可能与调节TLR2/4-NF-κB的表达有关。
OBJECTIVE: To observe the protective effect of rutaecarpine (Rut) on focal cerebral ischemia (p MCAO) in rats and further investigate the protective effect of Rut on TLR2 / 4 and NF- κB) expression. Methods: The model of permanent middle cerebral artery occlusion (p MCAO) was established by modified Koizumi method and divided into model group, sham operation group and Rut high, medium and low dose groups (10, 5 and 1 mg · kg -1 ). After 3 days of modeling, ip Rut, the corresponding volume of normal saline in the model and the sham-operated group were given. After 1 week continuous administration, the effect of Rut on the volume of cerebral infarction and the water content of brain tissue were observed. The expression of TLR2 / 4 and NF-κB in brain tissues were detected by Western blotting and immunohistochemistry. The levels of tumor necrosis factor-α (TNF-α) and interleukin-1β IL-1β) content. Results: After focal cerebral ischemia in rats, the volume of cerebral infarction and the water content of brain tissue increased. Compared with the sham-operated group, the expression of TLR2, TLR4 and NF-κB in ischemic area increased and the number of positive cells increased significantly Increased; serum TNF-α and IL-1β levels increased significantly (P <0.01). Compared with the model group, Rut significantly reduced the volume of cerebral infarction and the water content of brain tissue (P <0.05). The inhibition of TLR2 / 4-NF-κB signaling pathway was inhibited by Rut (P <0.05) IL-1β content was significantly lower (P <0.05). CONCLUSION: Rutaecarpine has obvious protective effect on focal cerebral ischemia in rats, and its mechanism may be related to the regulation of TLR2 / 4-NF-κB expression.