老年大鼠腹部手术后认知功能障碍海马中NRF2、γ-GCS、IL-6和TNF-α的表达及黄腐酚对其的影响

Expression of NRF2,γ-GCS,IL-6 and TNF-α in hippocampus after operation in aged rats and the effect of xanthohumol on them

目的老年大鼠腹部手术后认知功能障碍海马中核转录因子E2相关因子2(NRF2)、γ谷氨酸-半胱氨酸合成酶(γ-GCS)、白细胞介素6(IL-6)和肿瘤坏死因子α(TNF-α)的表达及黄腐酚对其的影响。方法将45只SD大鼠随机分为对照组(未行手术)、手术组(行腹部手术)和黄腐酚组(行腹部手术+注射黄腐酚)。黄腐酚组大鼠于术前1 h,术后6 h、第2天、第3天每日腹腔注射1 mg/kg的黄腐酚。各取5只大鼠,术前1天和术后第3天、第7天进行Morris水迷宫测试来检测各组大鼠认知能力。迷宫实验结束后,HE染色观察海马神经元密度,RT-PCR检测海马组织中NRF2和γ-GCS的mRNA,ELISA法检测IL-16和TNF-α的含量。结果术前第1天,对照组、手术组和黄腐酚组大鼠的逃逸潜伏期和穿越平台次数均无统计学意义(P>0.05);术后第3天和7天,手术组和黄腐酚组大鼠的认知能力低于对照组,而黄腐酚组大鼠的认知能力高于手术组,差异均有统计学意义(P<0.05);术后第7天,手术组神经元密度较对照组显著降低(P<0.05),黄腐酚组与对照组间差异不明显(P>0.05),且黄腐酚组高于手术组。与对照组相比,手术组和黄腐酚组中NRF2和γ-GCS mRNA均显著升高(P<0.05),且黄腐酚组高于手术组;同时,海马中IL-6和TNF-α含量较对照组均明显升高(P<0.05),而给予黄腐酚的海马中IL-6和TNF-α含量明显降低,与手术组比较差异有统计学意义(P<0.05)。结论黄腐酚能够改善脾脏切除术后大鼠的认知功能障碍,其作用机制可能与上调NRF2、γ-GCS和下调IL-6、TNF-α表达有关。

Objective The expression of NRF2,γ-GCS,IL-6 and TNF-αin the hippocampus of the aged rats and the effect of xanthohumol on them.Methods 45 SD rats were randomly divided into control group(no operation),operation group(abdominal operation)and xanthohumol group(abdominal operation+injection of xanthohumol).The rats in the pythol group were intraperitoneally injected with xanthohumol 1mg/kg before operation of 1 h,and after operation of 6 h,2 d,3 d.5 rats were taken,and the cognitive ability of each group were tested by the Morris water maze test after the operation of the 1 d,3 d,7 d.After the labyrinth experiment,the density of hippocampal neurons was detected by HE staining;NRF2 mRNA andγ-GCS mRNA of hippocampus were tested by RT-PCR.The content of IL-6 and TNF-αwere detected by ELISA.Results There was no statistical significance in the escape incubation period and the number of crossing platforms in the rats of the control group,the operation group and the xanthohumol group(P>0.05).The cognitive abilities of the operation group and the xanthohumol group were lower than that of the control group at 3 d and 7 d after operation,while the cognitive function of the rats in the xanthohumol group was higher than that in the operation group,and the difference was statistically significant(P<0.05).At postoperative 7 d,the density of neurons in the operation group was significantly lower than that in the control group(P<0.05),and there was no significant difference between the xanthohumol group and the control group(P>0.05),but the xanthohumol group was higher than that in the operation group.Compared with the control group,both NRF2 andγ-GCS mRNA in the operation group and the xanthohumol group increased significantly(P<0.05),and the xanthohumol group was higher than the operation group.At the same time,the content of IL-6 and TNF-αin the hippocampus was significantly higher than that in the control group(P<0.05).The content of IL-6 and TNF-αin hippocampus of pythol was significantly lower than that in the operation group(P<0.05).Conclusion Xanthohumol can improve the cognitive impairment of rats after splenectomy,and its mechanism may be related to up regulation of NRF2,γ-GCS and down regulation of IL-6 and TNF-α.