川芎嗪减轻大鼠心肌缺血再灌注损伤炎症反应及机制

The Effects of Ligustrazine on Attenuating Inflammatory Reaction of Myocardial Ischemia Reperfusion Injury in Rats and Its Mechanism

目的观察川芎嗪预处理对大鼠心肌缺血再灌注损伤炎症反应的影响并探讨其可能的机制。方法 48只雄性SD大鼠随机分为假手术组、缺血再灌注组、川芎嗪组、左旋-硝基-精氨酸甲酯组以及川芎嗪+左旋-硝基-精氨酸甲酯组,假手术组左前降支近端穿线但不结扎,其余四组给予结扎前降支缺血35 min,再灌注120 min。光镜观察大鼠心肌组织结构变化,测定缺血心肌组织超氧化物歧化酶活性和丙二醛含量及髓过氧化物酶、白细胞介素1β、一氧化氮含量,逆转录聚合酶链反应和免疫印迹法测定心肌内皮型一氧化氮合酶mRNA和蛋白的表达水平。结果与缺血再灌注组相比,川芎嗪预处理能减少心肌白细胞浸润,增加心肌组织超氧化物歧化酶活性,降低丙二醛含量及髓过氧化物酶活性,降低白细胞介素1β水平,增加一氧化氮含量及心肌内皮型一氧化氮合酶mRNA和蛋白的表达水平,左旋-硝基-精氨酸甲酯显著抑制上述指标的变化并取消了川芎嗪所致的内皮型一氧化氮合酶mRNA和蛋白表达水平的增加。结论川芎嗪预处理能减少大鼠心肌缺血再灌注损伤的炎症反应,其机制可能与上调内皮型一氧化氮合酶表达,增加内源性一氧化氮水平有关。

Aim To observe the effect of ligustrazine（tetramethylpyrazine,TMP） pretreatment on the inflammatory reaction of myocardial ischemia reperfusion（IR） injury in rats and to investigate the possible mechanism.Methods Forty-eight Sprague-Dawley rats were randomly divided into sham group,IR group,TMP pretreated group,NG-nitro-L-arginine methyl ester（L-NAME） group and TMP＋L-NAME group.All hearts except those in the sham group were subjected to 35 min ischemia followed by 120 min reperfusion.The myocardial structure was observed under microscope.The activity of myocardial superoxide dismutase（SOD） and the content of malondialdehyde（MDA）,myeloperoxidase（MPO）,interleukin-1β（IL-1β） and nitric oxide（NO） were measured.The expression of endothelial nitric oxide synthase（eNOS） was detected by reverse transcription polymerase chain reaction and Western blot.Results Compared with the IR group,the myocardial tissues of the TMP group showed an increase in the SOD activity,a decrease in the MDA content,the MPO activity and the level of IL-1β.TMP pretreatment also increased the NO level and alleviated the neutrophil infiltration.The expression of eNOS mRNA and protein in the myocardium of rats in the TMP group increased significantly compared with that in the IR group.However,these effects could be significantly reversed by L-NAME which abolished the increase of NO production and eNOS mRNA and protein expression brought by TMP.Conclusions Pretreatment of TMP attenuated the inflammatory reaction of myocardial IR in rats.The cardioprotective mechanism of TMP may relate to its effects of increasing the expression of eNOS and the level of NO.