莪术提取物对单纯疱疹病毒性脑炎模型小鼠脑血流动力学及氧化应激的作用

目的 探讨莪术提取物对单纯疱疹病毒性脑炎(Herpes simplex encephalitis,HSE)模型小鼠脑血流动力学及氧化应激的影响及其可能作用机制。方法 选取48只C57BL/6雄性小鼠脑部注射Ⅰ型单纯疱疹病毒建立HSE小鼠模型,造模成功小鼠随机分为模型组、莪术提取物低、高剂量(50、100 mg/kg)组、西药组(150 mg/kg阿昔洛韦)各12只,另设对照组12只; 实验期间记录小鼠一般情况和存活天数并计算生命延长率; 酶联免疫吸附法(Enzyme linked immunosorbent assay,ELISA)检测小鼠血清丙二醛(Malondialdehyde,MDA)、谷胱甘肽过氧化物酶(Glutathione peroxidase,GSH-Px)、超氧化物岐化酶(Superoxide dismutase,SOD)水平; 激光散斑成像系统检测小鼠脑血流变化; 苏木精-伊红染色法(Hematoxylin eosin staining,HE)染色观察小鼠脑组织病理学变化; 实时荧光定量聚合酶链反应法(Real time fluorescent quantitative polymerase chain rection,RT-qPCR)和蛋白质印迹法(Western blot)分别检测小鼠脑组织中核因子E2相关因子2(Nuclear factor erythroid-2-related factor 2,Nrf2)、血红素加氧酶1(Heme oxygenase 1,HO-1)mRNA和蛋白相对表达水平。结果 与模型组比较,莪术提取物低、高剂量组和西药组小鼠存活天数、GSH-Px,SOD水平、平均血流指数、Nrf2与HO-1 mRNA和蛋白相对表达水平升高,MDA水平降低(P<0.05); 与莪术提取物低剂量组比较,莪术提取物高剂量组和西药组小鼠存活天数、生命延长率、GSH-Px,SOD水平、平均血流指数、Nrf2与HO-1 mRNA和蛋白相对表达水平升高,MDA水平降低(P<0.05); 莪术提取物高剂量组以上指标水平与西药组比较无明显差异(P>0.05)。结论 莪术提取物能够降低HSE模型小鼠脑组织中氧化应激反应,提高脑血流指数,改善HSE模型小鼠脑组织损伤,其机制可能是通过调节Nrf2/HO-1信号通路而发挥作用。

Effects of zedoary turmeric extract on cerebral hemodynamics and oxidative stress in mice with herpes simplex virus encephalitis

ObjectiveTo investigate the effects of zedoary turmeric extract on cerebral hemodynamics and oxidative stress in herpes simplex encephalitis(HSE)mice and its possible mechanism.Methods Forty-eight C57BL/6 male mice were injected with herpes simplex virus type I(HSV-1)into the brain to establish the HSE mouse model. The successful mice were randomly divided into model group, low and high dose of zedoary turmeric extract(50, 100 mg?kg^-1)group, western medicine group(150 mg?kg^-1 acyclovir)and control group. During the experiment, the general condition and survival days of mice were recorded and the life extension rate was calculated. The levels of serum malondialdehyde(MDA), glutathione peroxidase(GSH-Px)and superoxide dismutase(SOD)were detected by ELISA. The changes of cerebral blood flow in mice were detected by laser speckle imaging system. HE staining was used to observe the histopathological changes of mouse brain.RT qPCR and Western blot were used to detect the mRNA and protein expression of nuclear factor E2 related factor 2(Nrf2)and heme oxygenase 1(HO-1)in mouse brain.Results Compared with the model group, the levels of survival days, GSH-Px, SOD, mean blood flow index, Nrf2 and HO-1 mRNA and protein expression were increased, and the levels of MDA were decreased in low, high dose of polydatin groups and western medicine group(P<0.05). Compared with the low dose of polydatin group, the levels of survival days, life prolongation rate, GSH-Px, SOD, mean blood flow index, Nrf2 and HO-1 mRNA and protein expression were increased, and the levels of MDA were decreased in low, high dose of polydatin groups and western medicine group(P<0.05). There was no significant difference in the above indexes between the high dose zedoary turmeric extract group and the western medicine group(P>0.05).Conclusion Zedoary turmeric extract can reduce oxidative stress response in mouse brain tissue, improve the cerebral blood flow index andbrain tissue injury in HSE mice, and its mechanism may be through regulating Nrf2/HO-1 signaling pathway.