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目的:探讨加减薯蓣丸对血管性痴呆(VD)大鼠海马CA1区细胞凋亡的影响及其可能的作用机制。方法:采用改良双侧颈总动脉永久阻断法(2-VO)制备VD大鼠模型,设VD模型组、加减薯蓣丸组、正常组及假手术组各20只。加减薯蓣丸组予10 g/(kg·d)剂量加减薯蓣丸灌胃,其余3组用等量生理盐水。灌胃12周后,Morris水迷宫行行为学检测,HE染色观察海马CA1区组织学改变,免疫组织化学法检测CREB表达的变化,Western blot法检测PTEN、Bcl-2蛋白的表达。结果:与正常组及假手术组比较,VD模型组大鼠的行为学表现下降(P<0.05),变性神经元增加(P=0.001),神经元总数减少(P=0.73),CREB和Bcl-2表达减少(P<0.01),PTEN表达升高(P<0.01);与VD模型组比较,加减薯蓣丸组大鼠的行为学表现改善(P<0.05),变性神经元减少(P=0.004)、神经元总数增加(P=0.78),CREB和Bcl-2表达增加(P<0.01),PTEN表达下降(P<0.01)。结论:VD大鼠空间记忆能力下降与CREB、Bcl-2表达下降及PTEN表达升高有关,加减薯蓣丸方可能通过调节VD大鼠海马区PTEN/CREB/Bcl-2信号通路的表达,改善VD大鼠的空间记忆能力。
Objective: To investigate the effect of adding and subtracting yuzhu pill on apoptosis in hippocampal CA1 area of vascular dementia (VD) rats and its possible mechanism. Methods: VD rat models were established by permanent bilateral carotid artery occlusion (2-VO) model. VD model group, plus and minus yuzhu pills group, normal group and sham operation group were divided into two groups. Addition and subtraction yam pills group 10 g / (kg · d) dose plus yam pills administered, and the remaining three groups with the same amount of saline. Twelve weeks after gavage, Morris water maze was used for behavioral testing. The histopathological changes of hippocampal CA1 region were observed by HE staining. The expression of CREB protein was detected by immunohistochemistry. The expressions of PTEN and Bcl-2 protein were detected by Western blot. Results: Compared with normal group and sham operation group, the behavior of VD model group decreased (P <0.05), degeneration neurons increased (P = 0.001), total number of neurons decreased (P = 0.73), CREB and Bcl (P <0.01). Compared with VD model group, the behavioral performance of rats in addition and subtraction group was significantly improved (P <0.05), and the number of degenerative neurons decreased (P <0.01) = 0.004). The total number of neurons increased (P = 0.78), the expression of CREB and Bcl-2 increased (P <0.01) and the expression of PTEN decreased (P <0.01). Conclusion: The decrease of spatial memory capacity of VD rats is related to the decrease of CREB and Bcl-2 expression and the increase of PTEN expression. The addition and subtraction of Yueshu pills can improve the expression of PTEN / CREB / Bcl-2 signal pathway in hippocampus of VD rats VD rats spatial memory ability.