加减薯蓣丸对血管性痴呆大鼠海马CA1区细胞凋亡及PTEN信号通路的影响

Effects of Modified Yam Pill on PTEN Signaling in Hippocampus of Vascular Dementia Rats

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 explore the effects of Modified Yam Pill on spatial memory and PTEN/CREB/Bcl -2 signaling in the hippocampal of vascular dementia rats. Methods ： Totally 80 male adult Wisatar rats were randomly divided into four groups , i. e. , the normal group, the sham - operation group, the VD model group and the Modified Yam Pill group. Decoction of Modified Yam Pill was poured into the stomach of the related group for 12 weeks. The spatial memory was tested by Morris after 12 weeks. Morphological changes of the hippocampal CA1 were observed by HE staining and the expression of CREB in the hippocampal CA1 region was detected using immunohistochemical assay after the spatial memo- ry test. The expressions of PTEN and Bcl - 2 in hippocampus were detected using Western blot. Results ： Compared with the normal group and the sham- operation group, the expressions of CREB and Bcl- 2 were decresed（P 〈 0. 01 ） while that of PTEN was increased. The escape latency was prolonged, times of crossing platform were decreased, the swimming speed was decreased,degenerated neurons increased（ P = 0. 001 ） and total neurons decreased in the VD model group（ P =0.73）. Compared with the VD model group, the expression of CREB,Bcl -2 was increased（P 〈 0. 01 ） while that of PTEN was decreased. The escape latency was shortened, times of crossing platform were incrseased, the swimming speed was increased, degenerated neurons decreased（ P = 0.004） and total neurons increased in the Modified Yam Pill group （ P = 0.78 ）. Conclusion ： The decline of spatial memory ability of VD rats is related to the decreasing expression of CREB and Modified Yam Pill could improve the ability of spatial memory and protect neurons from degeneration through PTEN! CREB/Bcl -2 singnaling in the hippocampus in VD rats.