超声空化增强川芎嗪对脑缺血再灌注损伤保护作用机制的研究

川芎的生物活性成分(川芎嗪)已广泛应用于治疗心脑血管疾病。基于谷氨酸诱导PC12细胞损伤建立脑缺血再灌注损伤的细胞模型,探讨超声增强川芎嗪对谷氨酸损伤PC12细胞的保护作用机制。研究结果表明,超声能进一步加强川芎嗪对细胞的保护,其主要作用机制为:(1)抑制氧化应激和细胞凋亡相关的Bcl-2蛋白和Bax蛋白的变化从而达到抗凋亡的效果;(2)降低炎症因子(TNF-α和IL-8)的表达,减轻炎症反应损伤;(3)适当的声压可以增强川芎嗪对谷氨酸损伤PC12细胞的保护作用,但过高的声压会引起细胞损伤,导致细胞凋亡。本文的工作表明超声能够增强川芎嗪对脑缺血再灌注损伤的保护作用,为临床脑缺血再灌注损伤的治疗提供了新治疗策略。 

Investigation on the mechanisms of neuroprotective effects of tetramethylpyrazine enhanced by ultrasound-induced cavitation activities

In traditional Chinese medicine, Ligusticum wallichii (Chuan Xiong) and its bioactive ingredient, tetramethylpyrazine (TMP), have been used to treat cardiovascular diseases. This work investigated whether ultrasound (US) exposure could enhance the protective effect of TMP against cerebral ischemia/reperfusion (I/R) injury. Glutamateinduced toxicity to pheochromocytoma (PC12) cells was used to model I/R injury. TMP was paired with US to examine whether this combination could alleviate glutamate induced cytotoxicity. The administration of TMP effectively protected cells against glutamate-induced apoptosis, which could be further enhanced by US-mediated sonoporation. The anti-apoptotic effect of TMP was associated with the inhibition of oxidative stress and a change in the levels of apoptosisrelated proteins, Bcl-2 and Bax. Furthermore, TMP reduced the expression of pro-inflammatory cytokines such as TNF-α and IL-8, which likely also contributes to its cytoprotective effects. This work suggests that ultrasound-enhanced TMP treatment might be a promising therapeutic strategy for ischemic stroke.