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目的:探讨黄芩茎叶黄酮(SSF)对β-淀粉样蛋白25-35(Aβ25-35)结合三氯化铝(Al Cl3)及重组人类转化生长因子-β1(RHTGF-β1)(复合Aβ)所致大鼠记忆障碍及抑制神经细胞凋亡的调节机制。方法:SD雄性大鼠手术d 1脑室注射RHTGF-β1,手术d 2开始上午脑室注射Aβ25-35,连续注射14 d,下午脑室注射Al Cl3,连续注射5 d,建立记忆障碍模型,术后d 45用Morris水迷宫进行记忆障碍模型筛选,术后d 49模型成功大鼠随机分为模型组和3个剂量SSF药物组。药物组大鼠分别灌胃35,70和140 mg·kg-1SSF,qd,在给药d 31~37进行Morris水迷宫学习、记忆能力测定。Western blot法测定神经细胞线粒体膜B细胞淋巴瘤/白血病-2(Bcl-2)和Bcl-2相关X蛋白(Bax)及胞液中COX4的蛋白表达;RT-PCR法测定神经细胞胞液中CytC和Caspase-9的mRNA的表达。结果:Morris水迷宫模型筛选结果显示,本实验大鼠模型成功率为98.3%。学习记忆能力测试显示,脑室注射复合Aβ明显引起大鼠记忆获得、记忆保持和记忆再现障碍;使神经细胞线粒体膜上Bcl-2蛋白表达水平明显降低、Bax蛋白表达水平及胞液中Cyto C和Caspase-9 mRNA表达水平都明显增加。而灌胃35,70和140 mg·kg-1SSF不同程度地逆转复合Aβ所致大鼠上述学习记忆障碍及线粒体膜Bcl-2和Bax及胞液中Cyto C和Caspase-9表达的异常改变。线粒体膜和胞液中COX4在各组中变化不明显。结论:SSF能够改善复合Aβ所致大鼠记忆障碍,其作用机制可能是通过抑制神经细胞凋亡和调节线粒体凋亡通路中凋亡因子完成的。
Objective: To investigate the effects of stems and leaves flavonoid (Sf) of Scutellaria baicalensis Georgi on the expression of Aβ25-35 combined with aluminum chloride (Al Cl3) and recombinant human transforming growth factor-β1 (Aβ) Induced memory impairment and inhibition of neuronal apoptosis. Methods: SD rats were injected intracerebroventricularly with RHTGF-β1 at d 1, and then injected intracerebroventricularly with Aβ25-35 at d 2 for 14 days. After intracerebroventricular injection of Al Cl 3 for consecutive 5 days, models of memory impairment were established. 45 Morris water maze for memory impairment model screening, after successful d 49 model rats were randomly divided into model group and three doses of SSF drug group. Rats in the drug group were administered with 35, 70 and 140 mg · kg-1 SSF qd, respectively. Morris water maze learning and memory ability were measured on d 31-37. Western blot was used to detect the protein expression of Bcl-2, Bcl-2 and COX4 in the cytosol of neuronal cells. The expression of COX4 in neuronal cells was measured by RT-PCR CytC and Caspase-9 mRNA expression. Results: Morris water maze model screening results show that the success rate of the experimental rat model was 98.3%. Learning and memory ability tests showed that intracerebroventricular injection of compound Aβ significantly induced memory impairment, memory retention and memory impairment in rats. The expression of Bcl-2 protein in the mitochondrial membrane of neurons was significantly decreased. The expression of Bax protein and cytosolic Cyto C Caspase-9 mRNA expression levels were significantly increased. However, intragastric administration of 35, 70 and 140 mg · kg-1 SSF reversed the above abnormal changes of learning and memory impairment and Cyto C and Caspase-9 expression in Bcl-2 and Bax mitochondrial membranes and cytosol induced by Aβ in rats. Mitochondrial membrane and cytosol COX4 in each group did not change significantly. Conclusion: SSF can improve the memory impairment induced by compound Aβ in rats. The mechanism may be through inhibiting the apoptosis of nerve cells and regulating the apoptosis factor in mitochondrial apoptosis pathway.