To explore the potential effects of andrographolide on chronic cerebral hypoperfusion (CCH)-induced neuronal damage as well as the underlying mechanisms. Rat CCH model was established by 2-vessel occlusion (2VO). The CCH rats received andrographolide treatment for 4 weeks. The neuron loss was detected by using neuronal nuclei (NeuN) immunofluorescent staining. The expression levels of phospho-phosphatase and tensin homolog deleted on chromosome ten (p-PTEN), protein kinase B (AKT), p-AKT, and cysteinyl aspartate specific proteinase-3 (Caspase-3) proteins were accessed by Western blotting. Moreover, the neuronal apoptosis of hippocampus tissues was detected via terminal deoxynucleotidyl transferase- mediated dUTP nick end labeling (TUNEL) staining. CCH reduced the number of NeuN-positive cells, while the number was significant increased after andrographolide treatment. CCH increased the proteins expression level of p-PTEN, Caspase-3, and decreased the p-AKT, which were reversed by andrographolide treatment. Furthermore, andrographolide treatment also down-regulated CCH-induced TUNEL-apoptosis rate. Our results suggest that the PTEN/AKT pathway may be modulated by andrographolide and the damaging effects of CCH on hippocampus may be ameliorated by andrographolide treatment. Andrographolide may act as a potential therapeutic approach for chronic ischemic insults.

中文翻译：

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穿心莲内酯可能通过PTEN / AKT信号通路对大鼠慢性脑灌注不足所致海马神经元的神经保护作用。

目的探讨穿心莲内酯对慢性脑灌注不足（CCH）诱导的神经元损伤的潜在作用及其潜在机制。通过2血管闭塞（2VO）建立大鼠CCH模型。CCH大鼠接受穿心莲内酯治疗4周。通过使用神经元核（NeuN）免疫荧光染色检测神经元丢失。通过Western印迹法检测在第10号染色体（p-PTEN），蛋白激酶B（AKT），p-AKT和半胱氨酸天冬氨酸特异性蛋白酶3（Caspase-3）蛋白上缺失的磷酸磷酸酶和张力蛋白同源物的表达水平。此外，通过末端脱氧核苷酸转移酶介导的dUTP缺口末端标记（TUNEL）染色检测了海马组织的神经元凋亡。CCH减少了NeuN阳性细胞的数量，穿心莲内酯治疗后该数目显着增加。CCH增加了p-PTEN，Caspase-3的蛋白表达水平，并降低了p-AKT，这被穿心莲内酯处理所逆转。此外，穿心莲内酯治疗还下调了CCH诱导的TUNEL凋亡率。我们的结果表明穿心莲内酯可以调节PTEN / AKT途径，穿心莲内酯治疗可以改善CCH对海马的破坏作用。穿心莲内酯可能作为慢性缺血性损伤的潜在治疗方法。我们的结果表明穿心莲内酯可以调节PTEN / AKT途径，穿心莲内酯治疗可以改善CCH对海马的破坏作用。穿心莲内酯可能作为慢性缺血性损伤的潜在治疗方法。我们的结果表明穿心莲内酯可以调节PTEN / AKT途径，穿心莲内酯治疗可以改善CCH对海马的破坏作用。穿心莲内酯可能作为慢性缺血性损伤的潜在治疗方法。