亚甲蓝对百草枯中毒大鼠急性肝损伤的保护作用及机制  

Methylene blue attenuates acute liver injury induced by paraquat in rats

作　　者：戴利[1] 庞庆丰[2] 张鹏[2] 秦迎松[3] 

机构地区：[1]徐州医学院研究生学院2012级,江苏徐州221004 [2]江南大学无锡医学院,江苏无锡214122 [3]徐州医学院病理生理学教研室

出　　处：《徐州医学院学报》2015年第3期146-151,共6页Acta Academiae Medicinae Xuzhou

基　　金：国家自然科学基金(81270126)；中央高校基本科研业务费专项资金

摘　　要：目的：探讨亚甲蓝对大鼠百草枯中毒诱导的急性肝损伤的保护作用并对保护机制进行研究。方法24只清洁级雄性成年 SD 大鼠随机分为正常组、亚甲蓝（MB）组、百草枯（PQ）组和亚甲蓝治疗（PQ ＋MB）组，每组6只。腹腔内注射 PQ 35 mg／kg 建立大鼠中毒模型，PQ ＋MB 组大鼠于造模2 h 后腹腔内注射 MB 2 mg／kg，MB 组大鼠腹腔内注射 MB 2 mg／kg，正常组大鼠腹腔内注射等量无菌生理盐水。治疗后48 h 收集大鼠血清检测谷丙转氨酶（alanine transaminase， ALT）、谷草转氨酶（aspartate aminotransferase， AST）和碱性磷酸酶（alkaline phospha－tase， ALP），肝组织用于病理学分析、髓过氧化物酶（myeloperoxidase， MPO）活性、丙二醛（malondialdehyde， MDA）含量、超氧化物歧化酶（superoxide dismutase，SOD）活性、三磷酸腺苷（adenosine triphosphate，ATP）含量和血红素加氧酶－1（heme oxygenase －1，HO －1）免疫组化检测。另取40只大鼠，按照上述分组方法评估72 h 内死亡时间和死亡率。结果与正常组和 MB 组比较，PQ 组 ALT 和 ALP 水平增高， MPO 活性增强，MDA 含量增加， SOD 活性降低，ATP 含量降低和 HO －1表达增加（P ＜0．05）；MB 治疗后能够改变上述生化指标变化，减轻肝病理形态学变化，与 PQ 组相比，PQ ＋MB 组 HO －1表达量增高，同时大鼠生存时间延长，差异均具有统计学意义（P ＜0．05）。结论MB 能够减轻氧化损伤和抑制炎症反应，对 PQ 诱导的大鼠急性肝损伤发挥保护作用。Objective To discuss the protective effects of methylene blue （MB） on paraquat （PQ） -induced acute liver injury and potential mechanisms.Methods A total of 24 male Sprague -Dawley rats were divided into four groups according to their different treatments （n =6）： a normal group intraperitioneally injected with sterile saline, a methylene blue （MB） group administrated with 2 mg/kg MB i.p.alone, a paraquat （PQ） model group exposed to 35 mg/kg PQ i. p.alone, and a treatment group receiving 2 mg/kg MB 2 hour after intraperitioneal injection of 35 mg/lg PQ.Then serum samples were collected from the rats two days after treatment to examine their levels of alanine transaminase （ALT）, aspartate aminotransferase （AST） and alkaline phosphatase （ALP）.The liver tissues were taken to determine the activities of myeloperoxidase （MPO） and superoxide dismutase （SOD） as well as the amounts of malondialdehyde （MDA） and adenosine triphosphate （ATP）, in addition to pathological analysis.The expression of hemeoxygenase -1 （HO -1） was measured by immunohistochemistry.Furthermore, another forty rats were used to examine their survival times and rates after exposure to the same agents mentioned above.Results Compared with the normal or MB group, the PQ group produced significant increases in the quantities of MDA and HO -1 as well as the activities of MPO, ALT and ALP, in comparison with reduced levels of SOD and ATP （P 〈0.05）, which were then reversed after MB treatment.Moreover, MB could alleviate PQ -induced pathological damages.Meanwhile, the combination of PQ and MB resulted in higher amounts of HO -1 and longer survival times than administration with PQ alone （P 〈0.05）.Conclusion MB can protect rats from PQ -induced acute liver injury, which may be associated with its abilities to relieve oxidative damages and in-hibit inflammation.

关 键 词：急性肝损伤 百草枯 亚甲蓝 

分 类 号：R363[医药卫生—病理学]