普罗布考通过TGF-β1/Smad 2/3通路减轻大鼠脑缺血再灌注损伤  

Probucol attenuate cerebral ischemia reperfusion injury via TGF-β1/Smad 2/3 pathway in rats

作　　者：曾洪艳[1] 彭宇婕 保丽玲[2] 

机构地区：[1]昆明医科大学海源学院组织学与胚胎学教研室,昆明650101 [2]昆明医科大学海源学院病理学教研室,昆明650101

出　　处：《解剖学杂志》2017年第3期278-282,291,共6页Chinese Journal of Anatomy

摘　　要：目的:探讨普罗布考对大鼠脑缺血再灌注(I/R)的影响及其可能机制。方法:线栓法建立大鼠大脑中动脉栓塞(MCAO)模型,用1.5、3 mg/kg普罗布考进行干预,将200只大鼠分为假手术组、I/R组、溶剂组、小剂量组(1.5 mg/kg)及大剂量组(3mg/kg)。术后15 min腹腔注射药物,于1、3、5 d和7 d取材。观察普罗布考对脑缺血再灌注炎性损伤急性期及恢复早期神经功能评分、梗死灶体积、脑组织水含量的影响,并用ELISA检测脑组织匀浆环氧酶(COX-2)和5脂氧酶(5-LOX)活性变化,免疫印迹检测各组TGF-β1和p-Smad2/3蛋白表达量的变化。结果:与假手术组比较,MCAO术后小鼠出现严重的神经功能障碍、脑水肿和脑梗死,COX-2和5-LOX蛋白表达显著升高,而TGF-β1和p-Smad2/3蛋白表达明显降低;与手术组比较,经普罗布考干预后,小鼠神经功能评分、脑水肿和脑梗死情况明显改善,COX-2和5-LOX蛋白表达明显降低,而TGF-β1和p-Smad2/3蛋白表达明显升高,且大剂量组优于小剂量组。结论:普罗布考能缓解大鼠脑缺血再灌注炎性损伤,其机制可能与激活TGF-β1/Smad2/3信号通路,抑制脑内COX-2与5-LOX的活性有关。Objective： To determine the effect of probucol on cerebral ischemia reperfusion（I/R） injury at different time points of acute phase in rats and investigate its possible mechanism. Methods： Middle cerebral artery occlusion （MCAO） model was established by Longa＇s method in rats. Then the rats were randomly divided into 5 groups： sham operation group, I/R group, vehicle group,low-and high-dose probueol intervention groups （1.5 and 3 mg/kg, given intraperitoneally 15 minutes after modelling, n= 15）. Neurological function was evaluated at different time points after ischemia reperfusion. The rats were sacrificed on 1 d, 3 d, 5 d and 7 d after surgery, and the brain tissues were harvested to investigate the infarct volume and brain water content. ELISA was used to determine the activities of eyclooxygenase （COX-2） and 5-1ipoxygenase （5-LOX） in brain tissues. Western blotting was used to detect the expression levels of transforming growth factor（TGF）-β1 and p-Smad 2/3. Results： Compared with the sham group, cerebral I/R injury induced severe neurological dysfunction, cerebral edema and cerebral infarction, induced the activities of COX-2 and 5-LOX, and inhibited the expression of TGF-β1 and p-Smad 2/3 proteins in brain homogenates. But probucol intervention obviously attenuated the injury, reduced the activities of COX-2 and 5-LOX, induced the expression of TGFq31 and p-Smad 2/3 proteins, and the high-dose group was superior to the low-dose group. Conclusion： Probucol has protective effect on inflammatory injury of acute injury in ischemia reperfusion injury rats, and the mechanism is related to the activation of TGF-β1/Smad 2/3 signal pathway and inhibition of the activity of COX-2 and 5-LOX in the brain.

关 键 词：脑缺血再灌注炎性损伤 大脑中动脉栓塞 普罗布考 环氧酶 5脂氧酶 转化生长因子β1 SMAD 2/3 大鼠 

分 类 号：R743[医药卫生—神经病学与精神病学]