Nrf-2基因过表达对急性胰腺炎大鼠胰腺的保护作用

The protective effect of Nrf2 gene overexpression on acute pancreatitis rats induced by lipopolysaccharide and cerulein

目的探讨Nrf-2基因过表达对急性胰腺炎大鼠胰腺的保护作用。方法32只雄性SD大鼠随机分为4组:正常对照组(NC)、Nrf-2过表达组(Nrf-2+/+)、胰腺炎组(AP)、Nrf-2过表达胰腺炎组(Nrf-2+/++AP)。各组均采用尾静脉注射慢病毒感染后,AP组和Nrf-2+/++AP组通过腹腔内注射蛙皮素和脂多糖造模;造模后24 h处死大鼠取材,ELISA法检测大鼠血清C-反应蛋白(CRP)含量;检测胰腺组织超氧化物歧化酶(SOD)、丙二醛(MAD)和髓过氧化物酶(MPO)水平;RT-PCR检测胰腺Nrf-2mRNA相对表达量;Western blot检测Nrf-2蛋白相对表达量;H&E染色观察大鼠胰腺组织细胞形态。结果AP组与NC组相比,大鼠血清C反应蛋白含量显著升高,SOD活性明显降低,MDA含量和MPO活性明显高于AP组,且AP组胰腺组织损伤较NC组明显增加;与AP组相比,Nrf-2过表达后,Nrf-2+/++AP组大鼠血清C反应蛋白含量显著降低,SOD活性明显升高,MDA含量和MPO活性明显低于AP组,且Nrf-2+/++AP组胰腺组织损伤较AP组有所缓解。结论过表达Nrf-2基因可通过降低急性胰腺炎大鼠CRP含量、MD A水平和MPO活性,提高SOD活性,缓解了大鼠胰腺损伤。

This study was performed to investigate the protective effect of nuclear factor E2-related factor 2(Nrf2) overexpression on the pancreas of rats with acute pancreatitis.Lentivirus infection is applied to overexpress Nrf-2 gene by tail intravenous injection,while intraperitoneal injection of lipopolysaccharide and cerulein was used to construct a model of acute pancreatitis.Serum C-reactive protein(CRP) was detected by ELISA;the levels of superoxide dismutase(SOD),malondialdehyde(MAD) and myeloperoxidase(MPO) were detected in pancreatic tissue.RT-PCR and Western blot were applied to detect the relative expression of pancreatic Nrf-2;H&E staining was used to observe the morphology of pancreatic tissue cells in rats.Compared with normal control group,acute pancreatitis group demonstrated a lower SOD activity but higher levels of C-reactive protein,MDA,MPO activity,and more severe pancreatic tissue damage.After Nrf-2 overexpressing,Nrf2+/++AP group showed significantly lower serum C-reactive protein content,observably increased SOD activity,notably lower MDA content and MPO activity,and the pancreatic tissue injury of Nrf2+/++AP group was alleviated,as compared with AP group.In conclusion,overexpression of Nrf-2 gene can relieve pancreatic injury by reducing CRP content,MDA level,MPO activity and improving SOD activity in AP rats.