论文部分内容阅读
目的:为探讨外源性载脂蛋白E(apoE)肽段对局灶性脑缺血再灌(I/R)的保护机制,观察apoE-1410拟肽对I/R小鼠脑组织磷酸化c-jun氨基端激酶(JNK)表达变化的影响。方法:实验选用160只雄性ICR小鼠,随机分为3组:假手术对照组(sham组),模型组(I/R组),apoE治疗组(apoE组),采用可逆性大脑中动脉栓塞(MCAO)模型,术后行神经功能评分。I/R3、6、12、24、48h行HE染色观察皮质区神经细胞的形态变化,并计算存活神经元的数目。利用WesternBlot法、免疫组织化学法检测p-c-jun的表达,行TUNEL法检测凋亡细胞数。结果:与对照组比较,模型组小鼠神经功能评分均降低,I/R12h后存活神经元数目明显减少;p-c-jun阳性反应术后3、6、12、24h显著增高(P<0.05);随缺血时间延长,凋亡细胞增多,并于48h达高峰(P<0.05)。与模型组比较,治疗组小鼠神经功能评分增加,各时相点p-c-jun和TUNEL表达均不同程度下调(P<0.05)。I/R3h至48h皮质区p-c-jun表达与TUNEL呈正相关(r=0.716,P<0.01)。结论:缺血侧皮质区p-c-jun表达的增强可诱导I/R后神经细胞凋亡;拟apoE-1410肽对I/R具有一定的治疗作用,其机制之一可能是通过抑制JNK活化实现的。
AIM: To investigate the protective mechanism of exogenous apolipoprotein E (apoE) on focal cerebral ischemia-reperfusion (I / R) and to observe the effect of apoE-1410 peptidomimetic on the phosphorylation of brain in I / R mice c-jun amino-terminal kinase (JNK) expression changes. Methods: Sixty male ICR mice were randomly divided into three groups: Sham group, model group (I / R group), apoE group (apoE group), reversible middle cerebral artery occlusion (MCAO) model, postoperative neurological function score. The morphological changes of cortical neurons were observed by HE staining at 6, 12, 24 and 48 hours after I / R, and the number of surviving neurons was calculated. Western blotting was used to detect the expression of p-c-jun by immunohistochemical method. The number of apoptotic cells was detected by TUNEL. Results: Compared with the control group, the neurological scores of the model group decreased and the number of surviving neurons decreased significantly after I / R12h. The positive rate of pc-jun positive group increased significantly at 3, 6, 12 and 24 hours after operation (P <0.05). With prolonged ischemia, apoptotic cells increased and peaked at 48h (P <0.05). Compared with the model group, the neurological score of the mice in the treatment group increased, and the expressions of p-c-jun and TUNEL at each time point decreased to different extents (P <0.05). The expression of p-c-jun in the cortex of I / R3h to 48h was positively correlated with TUNEL (r = 0.716, P <0.01). CONCLUSION: The enhanced expression of pc-jun in ischemic cortex can induce neuronal apoptosis after I / R. The mechanism of apoE-1410 peptide on I / R may be through the inhibition of JNK activation of.