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-αm RNA、IL-6 m RNA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-αm RNA、IL-6 m RNA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-αm RNA、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。
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-αand 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-αmRNA 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-αand IL-6,levels of MDA,SOD,TNF-αmRNA 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-αmRNA 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.
作者
郑伟
海军
宋晓雪
常虎林
杜立学
ZHENG Wei;HAI Jun;SONG Xiaoxue;CHANG Hulin;DU Lixue(Dept.of Hepatobiliary Surgery,Shaanxi Provincial People’s Hospital,Xi’an 710068,China)
出处
《中国药房》
CAS
北大核心
2018年第15期2068-2072,共5页
China Pharmacy
