绞股蓝总苷对大鼠脑缺血再灌注损伤及NF-κB p65信号通路的影响

Influence of gypenosides on the injury induced by ischemia-reperfusion and NF-κB p65 signaling pathway in rat brain

目的研究绞股蓝总苷(GPs)对大鼠脑缺血再灌注损伤的保护作用及可能机制。方法将65只SD大鼠随机分为假手术组、模型组、尼莫地平组(20 mg/kg/d)、GPs低剂量组(100 mg/kg/d)和高剂量组(200 mg/kg/d)。建立大鼠脑缺血2h-再灌注模型,待大鼠麻醉清醒后,根据神经功能评分筛选出模型成功的实验动物,按各组剂量连续灌胃7 d后,2,3,5–三苯基四唑化氯(TTC)染色法观察各组脑组织梗死体积;HE染色观察脑组织病理学变化;免疫组织化学法观察大鼠大脑皮层白细胞介素-1β(IL-1β)、单核细胞趋化蛋白-1(MCP-1)的表达及核因子-κB p65(NF-κB p65)核转位情况。结果与模型组比较,GPs低、高剂量组梗死体积小于模型组(P<0.01),且IL-1β和MCP-1表达降低(P<0.01),NF-κB p65核转位减少(P<0.01)。结论 GPs对脑缺血2 h–再灌注损伤大鼠具有保护作用,其机制与抑制NF-κB p65的激活,降低炎性因子IL-1β及MCP-1的表达有关。

Objective To investigate the protective effects and potential mechanism of gypenosides （GPs）on brain ischemia- reperfusion injury in rats. Methods Sixty -five SD rats were randomly divided into the sham group, ischemia - reperfusion model group, GPs low - dose （ 100 mg/kg/d） and high - dose （ 200 mg/kg/d） groups and nimodipine group（20 mg/kg/d）. Ischemia -reperfusion injury model was performed according to Zea Longa method and scored according to the neurological function standard. GPs were orally administrated for 7 days after ensuring the success in ischemia -reperfusion model. Brain sections were stained by TYC to evaluate the area of infarct lesion. The pathological changes of rat brain were observed by HE staining. The immunohistochemistry was performed to detect the expressions of interleukin - 1β （ IL - 1β）, monocyte chemotactic protein 1 （ MCP - 1 ） and the nuclear translocation of NF - KB in the cerebral cortex of rats. Results The areas of infarct lesions in GPs low -dose and high -dose groups were significantly smaller than those in the model group（ P 〈 O. 01 ）. Compared with the model group ,the expressions levels of IL - 1β and MCP - 1 were decreased and the nuclear translocation of NF - KB p65 were reduced significantly in the GPs low -dose and high -dose groups（ P 〈 0.01 ）. Conclusion GPs may improve the brain ischemia - reperfusion injury through inhibiting the activation of NF - KB signaling pathway and decreasing the expressions of inflammatory factors, such as IL - 1βand MCP - 1.