乙酰左旋肉碱对大鼠缺血性损伤及氧糖剥夺细胞模型的保护作用

Protective effects of acetyl-L-carnitine on ischemic injury and oxygen-glucose deprivation-induced cells

摘要:

目的：观察乙酰左旋肉碱（acetyl-L-carnitine，ALC）对大鼠缺血性脑损伤和氧糖剥夺细胞模型的保护作用，并探讨其可能的作用机制。方法：采用随机数字表法，将SD大鼠随机分为假手术组、模型组和ALC组，制备大鼠脑缺血模型。术前24 h ALC组腹腔注射ALC，模型组和假手术组注射等量磷酸缓冲液。术后6 h进行氯化三苯基四氮唑（2，3，5-triphenyltetrazolium chloride，TTC）染色，评价ALC对大鼠缺血性损伤的影响。体外培养PC12细胞，将细胞随机分为正常组、模型组和ALC组，建立体外氧糖剥夺模型。建模前24 h在ALC组加入ALC。建模后3 h分别通过ＭＴＴ法、TUNEL法、SYTOX染色检测细胞活力与细胞的凋亡、坏死情况；同时检测各组细胞超氧化物歧化酶（superoxide dismutase，SOD）、三磷酸腺苷酶（adenosine triphosphatase，ATPase）活性和丙二醛（maleic dialdehyde，MDA）含量的改变。结果：ALC预处理后，大鼠的TTC染色梗死灶面积较模型组明显减小（P<0.05）；细胞活力与氧糖剥夺模型组相比显著增加，坏死与凋亡的细胞数明显下降，SOD、ATPase活性增高，MDA含量下降（P<0.05）。结论：ALC预处理可以保护大鼠缺血性脑损伤，提高氧糖剥夺条件下的细胞活力，其机制可能与增强细胞抗氧化能力、改善细胞的能量代谢、减少细胞凋亡与坏死有关。

Abstract:

Objective：To study the protective effects of acetyl-L-carnitine（ALC） on ischemic brain injury in rats and oxygen-glucose deprivation（OGD） induced cells as well as the possible mechanisms. Methods：Using the table of random number，SD rats were di－vided into three groups：sham group，model group and ALC group. ALC and an equal volume of phosphate buffer were injected intraperitoneally for ALC，model and sham groups respectively at 24 h before cerebral ischemia rat model was made. TTC（2，3，5-Triphenyltetrazolium chloride） staining was used to assess the effects. In vitro，PC12 cells were divided into normal group，model group and ALC group. ALC was given at 24 h before OGD model being made. Cell viability，apoptosis and necrosis were analyzed using MTT assay，TUNEL，SYTOX staining respectively. Activities of adenosine triphosphatase（ATPase） and superoxide dismutase（SOD） as well as maleic dialdehyde（MDA） content were also detected. Results：After the pre-treatment of ALC，the infarction size was obviousely reduced（P<0.05）；in vitro，the cell viability，activities of SOD and ATPaes were increased，while the content of MDA，percentage of apoptotic and necrotic cells were decreased compared with those in OGD group（P<0.05）. Conclusions：These results suggested that ALC has protective effects on ischemic injury rats and OGD induced PC12 cells. The effects may be associated with the improvment of cell antioxidant capacity and energy metabolism as well as the supression of necrosis and apoptosis.