甲基莲心碱对肝缺血再灌注损伤模型小鼠氧化应激和炎症反应的影响
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篇名: 甲基莲心碱对肝缺血再灌注损伤模型小鼠氧化应激和炎症反应的影响
TITLE:
摘要: 目的:考察甲基莲心碱对小鼠肝缺血再灌注(I/R)损伤的保护作用及机制。方法:将40只小鼠随机分为假手术组(生理盐水)、模型组(生理盐水)和甲基莲心碱低、中、高剂量组(10、30、60 mg/kg),每组8只。每天灌胃给药1次,连续给药7 d。给药结束后,除假手术组外,其余各组小鼠均采用夹闭肝蒂60 min后再灌注6 h复制肝I/R损伤模型。造模结束后,检测各组小鼠血清中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、肿瘤坏死因子α(TNF-α)和白细胞介素6(IL-6)水平,苏木精-伊红染色后观察肝组织病理学变化并进行炎症评分,检测肝组织中丙二醛(MDA)、超氧化物歧化酶(SOD)、TNF-α mRNA、IL-6 mRNA及核转录因子κB p65(NF-κB p65)蛋白表达情况。结果:与假手术组比较,模型组小鼠血清中ALT、AST、TNF-α、IL-6以及肝组织中MDA、SOD、TNF-α mRNA、IL-6 mRNA和NF-κB p65蛋白表达水平均显著升高(P<0.05);肝组织间质有大量炎症细胞浸润、肝细胞坏死,炎症评分显著升高(P<0.05)。与模型组比较,除甲基莲心碱低剂量组小鼠血清中ALT、TNF-α和肝组织中TNF-α mRNA、MDA、   NF-κB p65蛋白表达水平以及肝组织炎症评分降低不显著外,其余各组小鼠上述指标水平均显著降低(P<0.05);甲基莲心碱中、高剂量组小鼠肝小叶结构完整,肝细胞形态基本正常,病理损伤得到显著改善。结论:甲基莲心碱对肝I/R损伤模型小鼠具有保护作用,且呈剂量相关性;其作用机制可能与减轻氧化应激、抑制炎症反应和降低肝组织中NF-κB p65蛋白的表达有关。
ABSTRACT: OBJECTIVE: To investigate the protective effect and mechanism of neferine on hepatic ischemia/reperfusion (I/R) injury in mice. METHODS: Totally 40 mice were randomly divided into sham operation group (normal saline), model group (normal saline), and neferine low-dose, middle-dose and high-dose groups (10, 30, 60 mg/kg), with 8 mice in each group. They were given relevant medicine intragastrically once a day for consecutive 7 d. After medication, except for sham operation group, mice in other groups were given occlusion of liver pedicle 60 min and then given perfusion for 6 h to induce hepatic I/R injury model. After modeling, the levels of ALT, AST, TNF-α and IL-6 were detected. The pathological change of hepatic tissue was observed after HE staining and the inflammation was scored. The levels of MDA, SOD, TNF-α mRNA and IL-6 mRNA, and the protein expression level of NF-κB p65 in hepatic tissue were determined. RESULTS: Compared with sham operation group, serum levels of ALT, AST, TNF-α and IL-6, levels of MDA, SOD, TNF-α mRNA and IL-6 mRNA and the protein expression level of NF-κB p65 in hepatic tissue were increased significantly in model group (P<0.05). There was a large number of inflammatory cells infiltration and hepatic cells necrosis, and the inflammation score increased significantly (P<0.05). Compared with model group, except that serum levels of ALT and TNF-α, levels of TNF-α mRNA and MDA, protein expression level of NF-κB p65 and inflammation score of hepatic tissue were not significantly reduced in neferine low-dose group, above indexes of other groups were decreased significantly (P<0.05). In neferine middle-dose and high-dose groups, the structure of hepatic lobules was complete, the morphology of hepatocytes was normal, and pathological injury had been significantly improved. CONCLUSIONS: Neferine shows protective effect on hepatic I/R injury model mice in dose-dependent manner, the mechanism of which may be associated with reducing oxidative stress, inhibiting inflammatory reaction and reducing the protein expression of NF-κB p65 in hepatic tissue.
期刊: 2018年第29卷第15期
作者: 郑伟,海军,宋晓雪,常虎林,杜立学
AUTHORS: ZHENG Wei,HAI Jun,SONG Xiaoxue,CHANG Hulin,DU Lixue
关键字: 甲基莲心碱;肝缺血再灌注损伤;小鼠;炎症反应;氧化应激;核转录因子κB p65
KEYWORDS: Neferine; Hepatic ischemia/reperfusion injury; Mice; Inflammation; Oxidative stress; NF-κB p65
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