p38MAPK信号通路在肢体缺血预处理脑保护中的作用  

The effects of p38MAPK signal transduction pathway in cerebral protection of limb ischemic preconditioning

作　　者：修丽梅[1] 李光来[1] 张晓敏[1] 曹丽君[2] 吉晨晖 

机构地区：[1]山西医科大学第二医院神经内科,太原030001 [2]山西医科大学,太原030001

出　　处：《中华临床医师杂志（电子版）》2015年第9期126-131,共6页Chinese Journal of Clinicians(Electronic Edition)

摘　　要：目的：应用大鼠大脑中动脉缺血再灌注模型研究无创性远端肢体缺血预处理（RLIP）对大鼠脑缺血再灌注损伤的作用，探讨RLIP是否通过降低p38MAPK信号通路的活性抑制神经细胞凋亡发挥脑保护的作用。方法36只健康雄性SD大鼠，体重200-250 g，随机分成3组（n=12）：假手术组（sham组）、缺血再灌注组（I/R组）、无创远端肢体缺血预处理组（RLIP组）。（1）Sham组：分离右侧的颈总动脉、颈内动脉、颈外动脉，但不阻断血流。（2）I/R组：参照Longa的线栓法制作大脑中动脉缺血再灌注（MCAO）模型，阻断大鼠右侧大脑中动脉2 h后再灌注24 h。（3）RLIP组：在大鼠右后肢根部用改良的自制血压袖带施行远端缺血预处理，缺血5 min，再灌注5 min，共3个循环，RLIP后即刻行大鼠右侧大脑中动脉阻塞再灌注，步骤同前。三组大鼠均再灌注24 h后行神经功能缺陷评分（NDS）；用TTC法测定脑梗死容积；HE染色观察海马CA1区椎体细胞的形态；免疫组织化学法测定海马CA1区P-p38MAPK蛋白、Caspase8蛋白及Caspase3蛋白的表达。结果（1）神经功能缺陷评分：sham组无神经功能缺陷；RLIP组比I/R组评分降低，但两组24h NDS评分中位数相同。（2）TTC染色：sham组无梗死体积，与I/R组相比，RLIP组脑梗死体积显著减小，差异有统计学意义（P＜0.05）。（3）HE染色：sham组海马CA1区椎体细胞形态正常，排列整齐、致密，为2-3层，细胞核圆而大，染色呈浅蓝色。I/R组椎体细胞数明显减少，细胞体积缩小，细胞核碎裂、溶解、染色加深，间质水肿明显。与I/R组比较，RLIP组海马CA1区椎体细胞层次较清楚，数目多且细胞形态较完整，间质水肿较轻。（4）免疫组织化学结果：与 I/R 组比较， RLIP组P-p38MAPK蛋白、Caspase8蛋白和Caspase3蛋白表达显著减少（P＜0.05），但两组蛋白的表达均明显高于sham组（P＜0.Objective To study the cerebral protective effects of noninvasive remote limb ischemic preconditioning （RLIP） against ischemia-reperfusion injury using the middle cerebral artery occlusion in rats and to investigate whether through lowering p38MAPK signal transduction pathway activity to inhibit the apoptosis of nerve cells contributes to cerebral protection. Methods Thirty-six healthy male Sprague-Dawley rats （weight 200-250 g） were randomly divided three groups （n=12, each group）： sham-operated group （sham group）, I/R group, RLIP group. In the sham group, only separate common carotid artery （CCA）, internal carotid artery （ICA） and external carotid artery （ECA）, but don’t block the blood flow. In the I/R group, rats were subjected to 2 h of right middle cerebral artery occlusion （MCAO） followed by 24 h of reperfusion. In the RLIP group, rats were accepted 3 cycles of 5 minutes ischemia followed by 5 minutes reperfusion on right hind limb at the beginning of MCAO. Evaluation of neurologic deficit scores was performed on 24 h after reperfusion by the method of Longa＆#39;s. Six rats were randomly selected to measure the cerebral infarction volume by TTC staining and another rats were observed tissue morphology of hippocampal CA1 region by HE staining. The expression of P-p38MAPK, Caspase8 and Caspase3 in the hippocampal CA1 region were determined by immunohistochemical analysis. Results There was no neurologic deficit in sham group. The NDS in RLIP group was lower than that in I/R, but there was no significant difference between them. TTC staining：There was no infarction volume in sham group, the cerebral infarction volume in RLIP group decreased significantly comparing with that in I/R group （P〈0.05）. HE staining showed that in the sham group, the pyramidal neuron of hippocampal CA1 region were aligned, dense, for 2-3 layers, its shape was normal and its cell nucleus was round and big, dyed in light blue. But the pyramidal neuron in the I/R group were dyed deepen, its

关 键 词：细胞凋亡 脑保护 肢体缺血预处理 P38MAPK信号通路 

分 类 号：R543.5[医药卫生—心血管疾病]