丹酚酸B对β-淀粉样蛋白介导原代培养皮层神经元毒性的保护作用

目的　观察一氧化氮(NO)在谷氨酸(Glu)，β-淀粉样蛋白［β-AP(1-40)］引起神经细胞损伤中的作用以及丹酚酸B(Sal B)对β-AP(1-40)引起的神经细胞损伤保护作用。方法　原代培养大鼠皮层神经元，建立了硝普钠(SNP),Glu,β-AP(1-40)等3种损伤模型，用形态学观察、MTT比色法、Griess法分别测定神经元活力，培养液中乳酸脱氢酶(LDH)漏出和NO释放。结果　Glu和β-AP(1-40)可以引起神经元NO的释放增加，造成神经毒性。nNOS在Glu的毒性中起重要作用，iNOS可能在Aβ_1-40的毒性中起作用。Sal B能显著增加细胞活力，降低LDH释放率,并剂量依赖地减少NO释放。 结论　NO介导了Glu和β-AP(1-40)的毒性，Sal B可以通过减少NO释放，改善β-AP(1-40)的毒性作用。

EFFECTS OF SALIVIANOLIC ACID B ON

AIM: To study the roles of nitric oxide (NO) and nitric oxide synthase (NOS) on the glutamate (Glu) and beta-amyloid peptide beta-AP (1-40)] mediated neurotoxicity in primary cultured fetal rat cortical neuron and the neuroprotective effects of salvianolic acid B (Sal B) against the beta-AP (1-40) and its mechanism of action. METHODS: With application of specific agonist and antagonist of NOS, establishment of the sodium nitroprusside (SNP), Glu and beta-AP (1-40) neurotoxicity model, the cell viability, lactate dehydrogenase (LDH) efflux and NO release were detected by using morphological observation, MTT stain, spectrophotometric measurement and Griess method, respectively, in primary cultured fetal rat cortical neurons. RESULTS: Glu and beta-AP (1-40) were shown to increase the NO release of the neuron. Furthermore, nNOS was found to play an important role in the neurotoxicity of glutamate, iNOS may probably be involved in the neurotoxicity of beta-AP (1-40). Sal B (0.01, 0.10, 1.00 microgram.L(-1)) was shown to increase the cell viability, decrease the LDH release rate and inhibit NO release in a dose-dependent manner. CONCLUSION: These results suggest that the neurotoxicity of Glu and beta-AP(1-40) may be partly mediated through different types of NOS. Sal B was found to prevent the beta-AP(1-40) toxicity by directly or indirectly decreasing NO release.