论文部分内容阅读
目的:探讨p38MAPK特异性抑制剂SB203580(SB)对缺血再灌注损伤心肌细胞的保护作用及对凋亡信号通路的影响。方法:选择45只250~300g雄性SD大鼠,通过阻断其左冠状动脉(冠脉)前降支(LAD)30min再灌注180min制备I/R损伤模型,随机分为3组(每组15只):溶剂对照组(Vehicle组)、低剂量SB预处理组(SB-L组)和高剂量SB预处理组(SB-H组)。同时选取15只同周龄SD大鼠仅穿线但不结扎(Sham组)。SB-L组和SB-H组分别于LAD结扎前30min注射50、100μg/kg SB,其余两组注射等体积的0.9%氯化钠溶液。分别在术前(T0)、缺血30min后(T1)、再灌注60min(T2)、120min(T3)及180min后(T4)检测各组血浆肿瘤坏死因子(TNF)-a水平,处死大鼠并通过TTC染色分析缺血程度和梗死程度,将心脏组织包埋并采用免疫组织化学技术切片染色方法检测心肌组织中细胞外信号调节激酶(extracellular signal-regulated kinase ERK)和C-Jun氨基末端激酶(C-Jun N-terminal kinase JNK)及凋亡细胞的表达。结果:与Sham组相比,Vehicle组除T0外的I/R其余时间点的TNF-a水平均升高(均P<0.05);SB处理后可减轻TNF-a的升高且改善心肌缺血及梗死程度,ERK表达较Vehicle组增强,JNK表达较Vehicle组减弱(均P<0.05),SB-H组的改善效果优于SB-L组(P<0.05)。结论:SB对心肌I/R损伤有改善作用,可降低心肌缺血及梗死程度,并促进ERK信号通路表达,抑制JNK信号通路的活化,抑制心肌细胞的凋亡。
AIM: To investigate the protective effect of SB203580 (SB), a specific inhibitor of p38MAPK, on cardiomyocytes injured by ischemia-reperfusion and its effect on apoptosis signal pathway. Methods: Forty-five male Sprague Dawley rats weighing 250-300g were randomly divided into 3 groups (15 rats in each group) by blocking the left anterior descending coronary artery (LAD) Only): vehicle control group, low dose SB pretreatment group (SB-L group) and high dose SB pretreatment group (SB-H group). At the same time, only 15 SD rats of the same age were selected but not ligated (Sham group). SB-L group and SB-H group were injected with 50, 100μg / kg SB 30min before LAD ligation, the other two groups were injected with an equal volume of 0.9% sodium chloride solution. The levels of tumor necrosis factor (TNF) -a in each group were measured before operation (T0), 30 min after ischemia (T1), 60 min (T2), 120 min (T3) and 180 min after reperfusion The degree of ischemia and infarct degree were analyzed by TTC staining. The heart tissues were embedded and immunohistochemistry was used to detect the extracellular signal-regulated kinase (ERK) and C-Jun N-terminal kinase (C-Jun N-terminal kinase JNK) and apoptotic cells. Results: Compared with Sham group, the levels of TNF-a in I / R group of Vehicle group except T0 were increased (all P <0.05); SB group could reduce the increase of TNF- Compared with Vehicle group, the expression of ERK increased, while the expression of ERK in JWH group was lower than that in Vehicle group (all P <0.05). The improvement effect of SB-H group was better than that of SB-L group (P <0.05). CONCLUSION: SB can improve myocardial I / R injury, reduce myocardial ischemia and infarction, promote the expression of ERK signaling pathway, inhibit the activation of JNK signaling pathway, and inhibit cardiomyocyte apoptosis.