[1]蒋 禹,王安康,白 赫,等.丝氨酸羟甲基转移酶对小鼠肝脏缺血再灌注的影响[J].南方医科大学学报,2020,(04):506-512.[doi:10.12122/j.issn.1673-4254.2020.04.09]
 Protective effect of serine methyltransferase against hepatic ischemia-reperfusion injuryin mice[J].Journal of Southern Medical University,2020,(04):506-512.[doi:10.12122/j.issn.1673-4254.2020.04.09]
点击复制

丝氨酸羟甲基转移酶对小鼠肝脏缺血再灌注的影响()
分享到:

《南方医科大学学报》[ISSN:1673-4254/CN:44-1627/R]

卷:
期数:
2020年04期
页码:
506-512
栏目:
出版日期:
2020-04-30

文章信息/Info

Title:
Protective effect of serine methyltransferase against hepatic ischemia-reperfusion injury in mice
作者:
蒋 禹王安康白 赫叶明新
关键词:
肝脏缺血再灌注丝氨酸羟甲基转移酶JNKNF-κB
Keywords:
hepatic ischemia-reperfusion serine hydroxymethyl transferase JNK nuclear factor-κB
DOI:
10.12122/j.issn.1673-4254.2020.04.09
文献标志码:
A
摘要:
目的 探索丝氨酸羟甲基转移酶2(SHMT2)在小鼠肝脏缺血再灌注损伤的表达及作用。方法 SPF级C57BL/6小鼠60只,分为正常组(sham)、生理盐水对照组(NS)、空载腺相关病毒组(AVV-GFP)、及腺相关病毒沉默组(AAV-SHMT2),每组15只。建模前2周尾静脉给予注射腺相关病毒及生理盐水,建立小鼠肝脏70%缺血再灌注模型。收集缺血再灌注模型小鼠的血清及肝组织。采用qPCR、Western blot、免疫荧光和免疫组化检测各组AST/ALT的浓度、SHMT2、JNK、NF-κB、Caspase-3及下游炎症因子表达水平的变化。并利用HE染色观察各组肝组织病理损伤,TUNEL法检测细胞凋亡。结果 肝脏缺血再灌注后SHMT2表达随时间升高,在24 h达最高(相对表达量为1.5,P<0.05)。肝脏缺血再灌注24 h后,AAV-SHMT2组AST/ALT水平含量(588/416 U/L)均明显高于对照组(416/345 U/L),空载组(387/321 U/L)(P<0.05)。AAV-SHMT2组与对照组和空载组相比,SHMT2水平明显降低(相对表达量为0.24,P<0.05),p-JNK,p-p65水平明显升高(相对表达量为0.80,0.97,P<0.05),炎症因子水平TNF-α、IL-1β与其保持一致升高(相对表达量为1.6,1.2,P<0.05)。空载组和对照组比较无统计性差异(P>0.05)。结论 SHMT2在肝脏缺血再灌注中有可能通过抑制JNK通路激活来缓减肝细胞的凋亡以及抑制NF-κB通路过度激活来减轻肝脏缺 血再灌注的损伤。
Abstract:
Objective To investigate the protective effect of serine hydroxymethyl transferase 2 (SHMT2) against hepatic ischemia-reperfusion injury in mice. Methods Sixty C57BL/6 mice were divided equally into sham-operated group, saline control group (NS), empty adeno-associated virus group (AVV-GFP), and adeno-associated virus silencing group (AAV-SHMT2). The adeno-associated virus and normal saline were injected into the tail vein of the mice 2 weeks before establishment of a 70% ischemia-reperfusion model in the liver. qPCR, Western blotting, immunofluorescence and immunohistochemistry were used to detect the changes of AST/ALT concentration, SHMT2, JNK, NF-κB, caspase-3 and downstream inflammatory factors in the mice, and HE staining was used to observe the pathological damage of the liver tissue in each group; the cell apoptosis in the liver was detected using TUNEL assay. Results The expression of SHMT2 increased with time after hepatic ischemia-reperfusion and reached the highest level at 24 h (the relative expression was 1.5, P<0.05). At 24 h after hepatic ischemia-reperfusion, the levels of AST/ALT in AAV-SHMT2 group (588/416 U/L) were significantly higher than those in the control group (416/345 U/L) and the empty vector group (387/321 U/L) (P<0.05). Compared with those in the control group and the empty vector group, the level of SHMT2 was significantly decreased in AAV-SHMT2 group (with a relative expression of 0.24, P<0.05), the levels of p-JNK and p-p65 were significantly increased (relative expression of 0.80 and 0.97, respectively, P<0.05), and the levels TNF-α and IL-1β were consistently elevated (relative expression levels of 1.6 and 1.2, respectively, P<0.05). No significant differences were found in these parameters between the empty vector group and the control group (P>0.05). Conclusion SHMT2 may alleviate liver cell apoptosis in mice with hepatic ischemia-reperfusion injury by inhibiting the activation of JNK pathway and excessive activation of NF-κB pathway to reduce hepatic damage.
更新日期/Last Update: 2020-04-30