【摘要】 目的 研究蒲公英提取物对自发性脑出血(ICH)大鼠的治疗作用及核因子E2相关因子2(Nrf2)/血红素加氧酶1(HO-1)信号通路的影响。方法 通过脑定位注射Ⅳ型胶原酶诱导建立48只ICH大鼠模型，随机分为模型组、蒲公英提取物组、Nrf2抑制剂(ML385)组和蒲公英提取物+ML385组，每组12只，另选12只大鼠作为假手术组。以药物分组处理后，进行大鼠神经功能损伤评分；检测大鼠血脑屏障功能、海马神经元细胞凋亡率、血清环氧化酶2(COX-2)、白细胞介素6(IL-6)、诱导型一氧化氮合酶(iNOS)及脑组织过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)、活性氧、丙二醛水平和Nrf2/HO-1信号通路蛋白表达。结果 与假手术组比较，模型组大鼠神经功能缺损评分、伊文思蓝渗出量、海马神经元细胞凋亡率、血清COX-2、IL-6、iNOS水平、脑组织活性氧、丙二醛水平显著升高(P<0.05),CAT、GSH-Px、Nrf2、HO-1蛋白表达水平显著降低(P<0.05)。与蒲公英提取物组比较，蒲公英提取物+ML385组大鼠神经功能评分[(2.54±0.23)分vs(1.43±0.19)分]、伊文思蓝渗出量[(22.15±3.61)ng/mg vs(6.54±1.24)ng/mg]、海马神经元细胞凋亡率[(31.97±5.26)%vs(3.51±0.94)%]、血清COX-2[(5.82±1.16)ng/ml vs(1.34±0.42)ng/ml]、IL-6[(1.47±0.31)ng/ml vs(0.43±0.14)ng/ml]、iNOS[(59.91±10.36)U/ml vs(13.94±3.78)U/ml]、脑组织活性氧[(4.70±0.45)U/kg vs(1.70±0.51)U/kg]、丙二醛水平[(3.72±0.52)nmol/mg vs(1.17±0.34)nmol/mg]显著升高(P<0.05),CAT[(2.54±0.59)U/mg vs(5.68±1.04)U/mg]、GSH-Px[(8.01±0.86)U/mg vs(16.97±3.03)U/mg]、Nrf2(0.67±0.13 vs 1.07±0.19)、HO-1(0.55±0.07 vs 0.86±0.10)蛋白表达水平显著降低(P<0.05)。结论 蒲公英提取物可通过激活Nrf2/HO-1信号通路增强ICH大鼠抗氧化活性，阻止炎症和氧化应激反应进展，抑制海马神经元细胞凋亡，修复血脑屏障功能，改善大鼠神经功能。更多还原

【Abstract】 Objective To investigate the therapeutic efficacy of dandelion extract on intracerebral hemorrhage(ICH) rats and its effect on nuclear factor erythroid 2 related factor 2(Nrf2)/heme oxygenase-1(HO-1) signaling pathway.Methods Stereotaxic intracranial injection of type IV collagenase was used to establish rat ICH model.Then 48 ICH rats were randomly divided into model group, dandelion extract group, Nrf2 inhibitor(ML385) group and dandelion extract+ML385 group, with 12 rats in each group. Another 12 rats served as sham operation group.After treatment, neurological deficits was evaluated and scored for all groups of rats.Blood-brain barrier(BBB) function, neuronal apoptotic rate in the hippocampus, serum levels of COX-2,IL-6 and iNOS,cerebral contents of CAT,GSH-Px, ROS and MAD,and protein levels of Nrf2/HO-1 signal pathway were detected.Results Compared with sham operation group, the neurological deficit score, Evans blue exudation, appptotic rate of hippocampal neurons, serum COX-2,IL-6,iNOS levels, brain tissue reactive oxygen species(ROS) and malondialdehyde level in the model group were significantly increased(P<0.05),and the expression levels of CAT,GSH-Px, Nrf2 and HO-1 proteins were significantly decreased(P<0.05).Compared with dandelion extract group, combination of dandelion extract and ML385 significantly increased the neurological deficit score(2.54±0.23 vs 1.43±0.19),Evans blue exudation [(22.15±3.61)ng/mg vs(6.54±1.24)ng/mg],apoptotic rate [(31.97±5.26)% vs(3.51±0.94)%],serum COX-2 [(5.82±1.16)ng/ml vs(1.34±0.42)ng/ml],IL-6 [(1.47±0.31)ng/ml vs(0.43±0.14)ng/ml] and iNOS levels [(59.91±10.36)U/ml vs(13.94±3.78)U/ml], brain tissue ROS [(4.70±0.45)U/kg vs(1.70±0.51)U/kg] and MDA levels [(3.72±0.52)nmol/mg vs(1.17±0.34)nmol/mg],and decreased expression levels of CAT [(2.54±0.59)U/mg vs(5.68±1.04)U/mg],GSH-Px [(8.01±0.86)U/mg vs(16.97±3.03)U/mg],Nrf2(0.67±0.13 vs 1.07±0.19) and HO-1(0.55±0.07 vs 0.86±0.10,P<0.05).Conclusion Dandelion extract can enhance the antioxidant activity in ICH rats by activating Nrf2/HO-1 signaling pathway, prevent the progression of inflammation and oxidative stress, inhibit neuronal apoptosis in hippocampus, repair blood-brain barrier function, and thus improve nerve function.更多还原