肝缺血再灌注对幼鼠血脑屏障通透性及脑组织细胞凋亡的影响OACSTPCD
Effects of hepatic ischemia-reperfusion on blood-brain barrier permeability and brain tissue apoptosis in young mice
目的 观察肝缺血再灌注(HIR)对幼鼠血脑屏障(BBB)通透性及脑组织细胞凋亡的影响.方法 将24只健康清洁级C57BL/6幼鼠随机分为假手术组、右旋糖苷10组和右旋糖苷40组,每组8只.右旋糖苷10组、右旋糖苷40组均采用夹闭肝左动脉及门静脉共干的方法建立HIR模型,于再灌注60 min后经下腔静脉注射相对分子质量分别为10、40 kD的右旋糖苷,假手术组组仅行开关腹、游离血管等操作.采用免疫荧光染色观察脑组织BBB通透性(以右旋糖苷通过率表示),采用Western blotting法检测脑组织BBB紧密连接蛋白相关指标闭合蛋白(Claudin)、咬合蛋白(Occludin)、β-连环蛋白(β-Catenin)、紧密连接蛋白1(ZO-1)相对表达量,采用TUNEL法检测脑组织细胞凋亡率.结果 与假手术组比较,右旋糖苷10组、右旋糖苷40组幼鼠脑组织右旋糖苷通过率、细胞凋亡率均升高,且右旋糖苷10组右旋糖苷通过率更高(P均<0.05).与假手术组比较,右旋糖苷10组、右旋糖苷40组幼鼠脑组织Claudin、Occludin、β-Catenin、ZO-1蛋白相对表达量均降低(P均<0.05),右旋糖苷10组、右旋糖苷40组上述指标比较差异均无统计学意义(P均>0.05).结论 HIR会导致幼鼠BBB通透性增加、脑组织细胞凋亡增多.
Objective To observe the effects of hepatic ischemia-reperfusion(HIR)on blood-brain barrier(BBB)permeability and brain tissue apoptosis in young mice.Methods Twenty-four healthy and clean grade C57BL/6 young mice were randomly divided into the sham operation group,dextran glycoside 10 group,and dextran glycoside 40 group,with 8 mice in each group.The HIR models were established by clamping the left hepatic artery and portal vein in mice of both dextran glycoside 10 and 40 groups.After 60 min of reperfusion,dextran glycoside with a molecular weight of 10 and 40 Kd was injected into the inferior vena cava,respectively.Mice in the sham operation group only underwent abdominal opening and closing,free blood vessels,and other procedures.Immunofluorescence staining was used to observe the per-meability of brain tissue BBB(expressed as the pass rate of dextran glycoside),Western blotting was used to detect the in-dicators related to BBB tight junction protein in brain tissues,including Claudin,Occludin and β-Catenin and tight junc-tion protein 1(ZO-1),and TUNEL method was used to detect the apoptosis rate of brain tissues.Results Compared with the sham operation group,the dextran glycoside 10 group and the dextran glycoside 40 group had higher passing rates of dextran glycoside and apoptosis rates in the brain tissues of young mice,and the low-dose group had a higher passing rate of dextran glycoside(all P<0.05).Compared with the sham operation group,the relative expression levels of Clau-din,Occludin,and β-Catenin and ZO-1 proteins decreased(all P<0.05),and there were no statistically significant differ-ences in the above indicators between the dextran glycoside 10 and 40 groups(all P>0.05).Conclusion HIR can lead to increased BBB permeability and increased apoptosis of brain tissues in young mice.
贾莉莉;喻文立;张涛;吕丹
天津市第一中心医院麻醉科,天津 300192南开大学生命科学院天津市第一中心医院疼痛科
临床医学
肝脏缺血再灌注损伤血脑屏障幼鼠
liver hepatic ischemia reperfusion injuryblood-brain barrieryoung mice
《山东医药》 2024 (011)
17-20 / 4
国家自然科学基金面上项目(82072219);天津市卫生健康科技项目(TJWJ2023QN025);天津市自然科学基金面上项目(21JCYB-JC00150).
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