核转录因子NF-E2相关因子2信号通路在PM_(2.5)致雌性大鼠生殖损伤中的作用

Effect of NF-E_2 related factor 2 pathway activation on PM_(2.5) induced reproductive injury in female rats

目的研究核转录因子NF-E2相关因子2(NF-E2 related factor 2, Nrf-2)信号通路在PM_(2.5)雌性生殖损伤中的作用。方法 30只雌性SD大鼠随机分为生理盐水对照组、1.5 mg/kg PM_(2.5)低剂量组和37.5 mg/kg PM_(2.5)高剂量组,连续暴露染毒10 d。ELISA试剂盒检测子宫中肿瘤坏死因子-α(tumor necrosis factor-α, TNF-α)、白介素-1β(interleukin 1 beta, IL-1β)和白介素-6(interleukin-6, IL-6)含量。荧光定量PCR (qPCR)检测子宫组织Nrf-2和血红素加氧酶-1(heme oxygenase-1, HO-1)mRNA表达水平。Western blot检测子宫组织Nrf-2和HO-1蛋白表达水平。结果低剂量组和高剂量组子宫TNF-α、IL-1β和IL-6含量均明显高于对照组(P<0.05);与低剂量组相比,高剂量组子宫TNF-α、IL-1β和IL-6含量明显升高,差异有显著性(P<0.05);且子宫组织炎性因子含量与PM_(2.5)暴露量正相关,随着PM_(2.5)暴露浓度的升高,TNF-a、IL-1β和IL-6含量不断升高(r=0.870、0.847和0.855)。荧光定量PCR和western blot检测结果显示,低剂量组和高剂量组子宫组织中Nrf-2和HO-1的mRAN表达水平和蛋白表达水平均明显高于对照组,差异有显著性(P<0.05)。结论雌鼠暴露PM_(2.5)后,Nrf-2信号通路被激活,但PM_(2.5)依然能诱发子宫炎症反应,造成子宫组织损伤。

Objective To study the effect of NF-E2 related factor 2(Nrf-2)pathway activation on particulate matter 2.5(PM 2.5)-induced reproduction injury in female rats.Methods Thirty Sprague Dawley rats were randomly divided into control(normal saline),low dose exposure(1.5 mg/kg PM 2.5),and high dose exposure(37.5 mg/kg PM 2.5)groups.The levels of tumor necrosis factor-α(TNF-α),interleukin 1-β(IL-1β),and interleukin-6(IL-6)were measured by enzyme-linked immunosorbent assay.The mRNA and protein expression of Nrf-2 and heme oxygenase-1(HO-1)were also examined by qPCR and western blot.Results There was a significant increase in TNF-α,IL-1β,and IL-6 expression in the low dose and high dose exposure groups compared with the control groups(P<0.05).The expression levels were also increased with increasing dose of PM 2.5(r=0.870,0.847,and 0.855,respectively).Both the mRNA and protein expressions of Nrf-2 and HO-1 were also significantly increased in the low dose and high dose exposure groups compared with controls(P<0.05).Conclusions The Nrf-2 signaling pathway is activated following exposure of PM 2.5 in female rats,although PM 2.5 can still induce uterine inflammation and injury.