摘要
目的探讨氟伐他汀对大鼠脑缺血再灌注后缺血侧皮质区claudin-5和occludin表达的影响。方法成年雄性SD大鼠随机分为假手术组、模型组和实验组,每组16只。假手术组和模型组均给予0.9%Na Cl;实验组给予10mg·kg^-1·d^-1氟伐他汀。3组大鼠均连续灌胃14 d。14 d后,模型组和实验组用Longa线栓法制作脑缺血再灌注损伤模型;假手术组接受相似手术处理,但是不插入线栓。脑缺血2 h再灌注24 h后,用伊文氏蓝(EB)法测定血脑屏障通透性变化,用反转录聚合酶链反应和印迹法检测缺血侧皮质区claudin-5和occludin的mRNA及蛋白表达水平。结果假手术组、模型组和实验组的EB含量分别为(1.95±0.06),(5.74±0.37)和(4.35±0.28),claudin-5 mRNA表达的光密度值分别为(0.45±0.06),(0.17±0.03)和(0.31±0.04),occludin mRNA表达的光密度值分别为(0.75±0.09),(0.24±0.04)和(0.51±0.07),claudin-5蛋白表达的光密度值分别为(0.83±0.06),(0.36±0.03)和(0.53±0.04),occludin蛋白表达的光密度值分别为(0.78±0.05),(0.31±0.02)和(0.62±0.07),模型组的上述指标与假手术组和实验组比较,差异均有统计学意义(均P<0.05)。结论氟伐他汀可通过增加claudin-5和occludin的表达来维持血脑屏障通透性,从而发挥脑保护的作用。
Objective To investigate the effect of fluvastatin on the expressions of claudin-5 and occludin on ischemic brain tissue in rats with focal cerebral ischemia-reperfusion injury(I/R).Methods Rats were randomly assigned into sham-operation group,model group and experimental group.Before making a model,the rats in the experimental group were lavaged with fluvastatin 10 mg·kg^-1·d^-1,once a day for 14 consecutive days.The rats in the sham-operation group and model group were lavaged with 0.9%NaCl.The middle cerebral artery occlusion I/R model was made by the modified Zea-Longa wire bolt method,while the sham-operation group underwent similar surgical procedures without inserting a wire plug.The blood-brain barrier permeability was detected by Evans Blue(EB)test.The expressions of claudin-5 and occludin mRNA and protein were measured by reverse transcription-polymerase chain reaction and Western blotting.Results The EB content in sham-operation group,model group and experimental group were(1.95±0.06),(5.74±0.37)and(4.35±0.28),the expressions of claudin-5 mRNA(optical density,OD)in the three groups were(0.45±0.06),(0.17±0.03)and(0.31±0.04),the expressions of occludin mRNA(OD)in the three groups were(0.75±0.09),(0.24±0.04)and(0.51±0.07),the expressions of claudin-5 protein(OD)in the three groups were(0.83±0.06),(0.36±0.03)and(0.53±0.04),the expressions of occludin protein(OD)in the three groups were(0.78±0.05),(0.31±0.02)and(0.62±0.07).The above indexes in the model group were significantly different from those in sham-operation group and experimental group(all P<0.05).Conclusion Fluvastatin can protect the brain by increasing the expressions of claudin-5 and occludin to maintain the permeability of blood-brain barrier.
作者
李国前
王杰华
苏钦坡
黄清宇
陈渊洁
杨小霞
LI Guo-qian;WANG Jie-hua;SU Qin-po;HUANG Qing-yu;CHEN Yuan-jie;YANG Xiao-xia(Department of Medicine Neurology,Quanzhou First Affiliated Hospital of Fujian Medical University,Quanzhou 362000,Fujian Province,China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2020年第3期264-266,共3页
The Chinese Journal of Clinical Pharmacology
基金
福建省教育厅B类课题基金资助项目(JB13303)
泉州市卫生计生科研课题资助项目(201605).