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目的:观察穿心莲内酯对慢性脑缺血大鼠认知功能的影响,探讨穿心莲内酯对脑的保护作用机制。方法:健康雄性SD大鼠48只,3-4月龄,体重250-300g,随机分成4组(n=12):假手术组(SH组)、慢性脑缺血组(IS组)、IS+二甲基亚砜组(DMSO组)和IS+穿心莲内酯组(AND组)。IS组、DMSO组和AND组采用永久结扎双侧颈总动脉法制备大鼠慢性缺血模型,DMSO组和AND组分别于双侧颈总动脉结扎后3,12,24,48h时腹腔注射0.2ml的5%DSMO和0.2ml含有10mg/kg穿心莲内酯的5%DSMO,IS组大鼠在术后相同时间点腹腔内注射等体积的生理盐水,SH仅穿线,不结扎。2周后进行Morris水迷宫测试认知能力;HE染色观察海马CA1区神经细胞形态,TUNEL染色法检测大鼠神经细胞凋亡,Western blotting检测海马组织Bcl-2蛋白的表达。结果:与SH比较,IS组和DMSO组于定位航行实验第2-5天、AND组于实验第2天逃避潜伏期延长,IS组、DMSO组、AND组第1象限停留时间缩短,细胞凋亡率增加,Bcl-2表达上调(P<0.05);与IS组比较,AND组于定位航行实验第3-5天逃避潜伏期缩短,第1象限停留时间延长,细胞凋亡率降低,Bcl-2表达上调(P<0.05);IS组与DMSO组间比较上述各指标差异无统计学意义(P>0.05)。结论:穿心莲内酯可改善慢性脑缺血大鼠认知功能,其机制可能与增加抗凋亡蛋白Bcl-2表达、减少神经细胞凋亡有关。
Objective: To observe the effects of andrographolide on cognitive function in rats with chronic cerebral hypoperfusion and to explore the protective mechanism of andrographolide on the brain. Methods: Forty-eight healthy male Sprague-Dawley rats were randomly divided into 4 groups (n = 12): sham operation group (SH group), chronic cerebral ischemia group (IS group), IS + Dimethyl sulfoxide group (DMSO group) and IS + andrographolide group (AND group). The rats in IS group, DMSO group and AND group were subjected to permanent ligation of the common carotid arteries to establish a chronic ischemic model in rats. DMSO group and AND group were intraperitoneally injected 0.2, 3, 12, 24 and 48 hours after ligation of bilateral common carotid artery ml of 5% DSMO and 0.2 ml of 5% DSMO containing 10 mg / kg of andrographolide. IS rats were injected intraperitoneally with equal volume of normal saline at the same time point after surgery. Morris water maze test was performed after 2 weeks. The morphology of neurons in hippocampal CA1 area was observed by HE staining. Neuronal apoptosis was detected by TUNEL staining. The expression of Bcl-2 protein in hippocampus was detected by Western blotting. Results: Compared with SH group, the IS group and DMSO group were on the 2nd to 5th days of positioning navigation experiment, and the AND group on the 2nd day of the experiment escaped the latency. The residence time in IS group, DMSO group and AND group 1 was shortened and apoptosis (P <0.05). Compared with the IS group, the latency of escape in AND group was shortened on the 3rd to 5th days of positioning navigation experiment, and the prolongation of residence time in the first quadrant decreased the apoptosis rate of Bcl-2 (P <0.05). There was no significant difference between the IS and DMSO groups (P> 0.05). Conclusion: Andrographolide can improve the cognitive function in rats with chronic cerebral ischemia. Its mechanism may be related to increasing the expression of anti-apoptotic protein Bcl-2 and reducing the apoptosis of nerve cells.