p38MAPK信号转导通路参与血管性痴呆大鼠海马细胞凋亡机制及Egb761保护作用的研究

P38MAPK involved in the mechanism of apoptosis in the hippocampus of vascular dementia rats and the protective role of Egb761

目的观察应用银杏叶提取物(extract of ginkgo biloba,Egb761)后血管性痴呆(vascular dementia,VD)大鼠空间认知功能的变化、海马细胞凋亡及海马中p38MAPK磷酸化表达的变化,探讨银杏叶提取物对大鼠海马的保护作用机制。方法应用用两血管法制作VD大鼠模型,将60只雄性Wistar大鼠随机分成假手术组(SOG组)、VD组和Egb组。Egb组大鼠给予Egb761100 mg·kg-1·d-1腹腔注射,VD组和SOG组给予等量的2ml生理盐水,一月后测试各组大鼠的空间认知能力,TUNEL法检测海马CA1区细胞凋亡,蛋白印迹法观察大鼠海马区p38MAPK磷酸化变化。计数资料采用t检验,P<0.05为差异有统计学意义。结果 1,2,3 dEgb组大鼠隐蔽平台逃避潜伏期[分别为(47.72±6.91)s、(42.84±4.19)s、(36.49±3.16)s]明显小于VD组隐蔽平台逃避潜伏期[(86.25±7.57)s、(79.17±8.43)s、(77.84±6.28)s],差异有统计学意义(P<0.05);Egb761组大鼠原平台象限时间[(27.19±4.73)s]大于VD组[(19.26±4.16)s],差异有统计学意义(P<0.05)。大鼠海马CA1区细胞凋亡、磷酸化p38MAPK的表达的比较:Egb组明显低于VD模型组,差异有统计学意义(P<0.05)。结论 Egb761可能是通过减少磷酸化P38MAPK的表达而抑制p38MAPK信号转导通路,显著改善VD大鼠的学习记忆能力,同时抑制海马区细胞凋亡,这可能是其参与血管性痴呆治疗的作用机制之一。

Objective To study the effects of Egb761 on cognitive function of rat model of vascular dementia （ VD）, the expression of p- p38MAPK and apoptosis in hippocampus, so as to discuss the protective role of Egb761 to hippocampus. Methods In this study VD model was established by two vascular method, in which 60 male Wistar rats were randomly di- vided into sham operation group, VD group and Egb group. Rats in Egb group were given 100 mg ·kg-1·d-1dose Egb761 by intraperitoneal injection, moreover rats inVD group and sham operation group were given the same dose of normal saline. The cognitive function of each rat was tested, and apoptosis was observed in hippocampal CAI region by TUNEL method, as well as the expression of p - p38MAPK in＇the hippocampus by Western blot method one month later. Measurement duta were processed by t - test,the result of P 〈 0. 05 showed significame differences. Results The hidden platform escape latency of Egb group on d l, d2 and d3 was （47.72 ±. 6.91 ）s, （42.84 ± 4, 19）s and （36.49 ± 3.16）s respective- ly, which was significantly shorter than that of VD group [ （ 86.25± 7.57） s, （79.17 ± 8.43 ） s, （77.84 ± 6.28） s ] （ P 〈 0.05 ） . The former platform quadrant time of Egb group was significantly prolonged than that of VD group [ （27.19 ± 4. 73 ） s versus （ 19.26 ± 4.16） s I （ P 〈 0.05 ）. Egb group was significantly lower than VD group in apoptosis and the expression of p38MAPK phospfiorytation in hippocampus （ P 〈 0.05 ）. Conclusions Egb761 can significantly improve the learning and memory ability of rats model of vascular dementia, and reduce apoptosis in the hippocampus by the inhibition of the p38MAPK pathway. This may be one of the ways involved in the treatment of vascular dementia.