短期禁食减轻小鼠肝脏缺血再灌注损伤的作用及其机制  

Role of short-term starvation in alleviating hepatic ischemia-reperfusion injury in mice and possible mechanismof action

作　　者：周俊晶 秦建杰 吕凌 周浩明 张峰 

机构地区：[1]南京医科大学第一临床医学院肝移植中心,210029

出　　处：《中华肝脏病杂志》2018年第1期42-47,共6页Chinese Journal of Hepatology

摘　　要：目的观察短期禁食对小鼠肝脏缺血再灌注损伤的作用，并探索其作用机制。方法将8周龄野生型C57BL／6雄性小鼠按照数字随机法分为75％肝缺血再灌注（IR）损伤组（IR组）、短期禁食＋75％肝IR损伤组（STS组）、sirtinol＋短期禁食＋75％肝IR损伤组（SIR组），并分别设立假手术组（IR—Sham组、STS—Sham组和SIR～Sham组）。检查各组小鼠血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）水平、肝组织形态学改变情况，及肝组织沉默信息调节因子2相关酶1（Sirtl）、微管相关蛋白1轻链3B（LC3B）、P62蛋白表达情况与LC3B荧光染色情况。多组数据比较采用方差分析法，两组间数据比较用t检验。结果与IR组相比，STS组小鼠ALT[（3152．7±735．6）U／L与（8414．2±1052．2）U／L，f=10．00，p〈0．01】和AST[（3577．0±714．0）U／L与（10845．8±1145．7）U／L，f=13．19，JD〈0．01]水平均显著降低；肝组织病理学损伤明显减轻（Suzuki评分为1．50±0．55与3．50-4-0．55，t=6．33，P〈0．01）；而SIR组ALT[（7002．7±1485．2）U／L】和AST[（8980．7±1739．1）U／L]水平再次升高，与STS组相比，差异均有统计学意义[t=5．69，p〈0．01（ALT）；t=7．04，p〈0．0l（AST）]，病理学损伤也较STS组明显加重（Suzuki评分为3．33±0．52与1．50±0．55，f=5．97，p〈0．01）。STS组及STS—Sham组肝组织中Sirtl基因及蛋白表达水平分别较IR组及IR—Sham组明显提高，LC3B蛋白表达水平明显提高，P62蛋白表达水平明显下降，LC3B染色阳性细胞比率明显升高（22．83％±5．19％与10．16％土3．060／0，t=5．15，p〈0．01；22．17％±4．83％与10．83％±1．94％，t=5．33，JD〈0．01）；而在sIR组及SIR—Sham组肝组织中，Sirtl表达水平较STS组及STS—Sham组显著下降，LC3B蛋白表达水平显著下降，P62蛋白表达水平显著提高，LC3B染色阳性细胞�Objective To investigate the role of short-term starvation （STS） in alleviating hepatic ischemia-reperfusion injury in mice and possible mechanism of action. Methods Wild-type male C57BL/6 mice aged 8 weeks were randomly divided into 75% hepatic ischemia-reperfusion injury group （1R group）, STS＋75% hepatic ischemia-reperfusion injury group （STS group）, and sirtinol＋STS＋75% hepatic ischemia-reperfusion injury group （SIR group）, using a random number table, and sham-operation groups （IR-Sham group, STS-Sham group, and SiR-Sham group） were also established. The serum levels of alanine aminotransferase （ALT） and aspartate anfinotransferase （AST） were measured, and the histomorphological changes of the liver were observed,as well as the expression of Sirtl, LC3B, and P62 proteins in liver tissue and the results of LC3B fluorescence staining. An analysis of variance was used for comparison of data between multiple groups, and the t-test was used for comparison of data between two groups. Results Compared with the IR group, the STS group had significant reductions in the serum levels of ALT （3 152.7 ± 735.6 U/L vs 8 414.2 ± 1 052.2 U/L,P 〈 0.01） andAST （3 577.0 -± 714.0 U/L vs 10 845.8 ± 1 145.7 U/L, P 〈 0.01） and significant alleviation of liver pathological injury （Suzuki score： 1.50±0.55 vs 3.50±0.55,P 〈 0.01）. Compared with the STS group, the SIR group had significant increases in the serum levels of ALT （7 002.7 -± 1 485.2 U/L vs 3 152.7 ± 735.6 U/L, P 〈 0.01） and AST （8 980.7 ± 1 739.1 U/L vs 3 577.0 ± 714.0 U/L, P 〈 0.01） and significant exacerbation of liver pathological injury （Suzuki score： 3.33 ± 0.52 vs 1.50 ± 0.55, P 〈 0.01）. Compared with the IR group and the IR-Sham group, the STS group and the STS-Sham group had significant increases in the mRNA and protein expression of Sirtl and the protein expression of LC3B and a significant reduction in the protein expression of P62, as well as a significant increase in the percent

关 键 词：缺血 再灌注损伤 短期禁食 沉默信息调节因子2相关酶1 自噬 

分 类 号：R575[医药卫生—消化系统]