摘要
目的探讨黄皮果提取物(EFCL)对小鼠急性乙醇中毒致肝损伤的保护作用及其可能的作用机制。方法 ICR小鼠40只,随机分为正常对照、模型及EFCL 1.5和3.0 g·kg-1组。EFCL 1.5和3.0 g·kg-1组小鼠分别ig给予相应剂量的EFCL;30 min后ig给予52℃二锅头白酒12 ml.kg-1;24 h后处死小鼠,制备血清,取肝组织制备10%肝组织匀浆,采用试剂盒方法检测血清丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)活性,以及肝组织匀浆中超氧化物歧化酶(SOD)活性、丙二醛(MDA)和谷胱甘肽(GSH)含量,常规HE染色和淀粉酶-过碘酸希夫法染色观察肝组织病理形态改变,并用免疫组织化学法测定肝组织中NF-κB和α-平滑肌肌动蛋白(α-SMA)的表达。结果与正常对照组比较,模型对照组小鼠血清ALT和AST活性分别升高28.0%和28.9%(P<0.01),肝组织匀浆中SOD活性和GSH含量分别由(706±46)kU·g-1蛋白和(251±61)mg.g-1蛋白降低至(515±68)kU·g-1蛋白和(126±18)mg.g-1蛋白,而MDA含量由(204±21)μmol·g-1蛋白升高至(258±50)μmol·g-1蛋白(P<0.05);肝组织中NF-κB和α-SMA表达增加(P<0.01)。与模型对照组比较,EFCL 1.5和3.0 g·kg-1组小鼠血清ALT活性分别降低了18.3%和19.8%,血清中AST活性分别降低了6.4%和9.7%(P<0.05,P<0.01);EFCL 3.0 g·kg-1组肝组织匀浆中GSH水平和SOD活性分别升高了61.4%和14.8%(P<0.05,P<0.01)。肝组织中NF-κB和α-SMA的表达水平明显低于模型对照组(P<0.01)。肝组织病理形态检测可见,EFCL 1.5和3.0 g·kg-1组小鼠对乙醇引起的肝细胞脂肪样变、水样变和炎症细胞浸润等均有明显改善。结论 EFCL对小鼠急性乙醇中毒所致肝损伤具有保护作用,其机制可能与升高抗氧化酶活性、促进自由基清除、降低NF-κB的表达及抑制肝星状细胞活化有关。
OBJECTIVE To study the protective effect of the extract from fruit of Clausena lansium （Lout.） Skeels （EFCL） against acute alcohol-induced hepatotoxicity in mice. METHODS The mouse model was established to use Red Star wine, its ethanol content was 52% by volume. Forty ICR mice were divided into four groups randomly： normal, model, EFCL 1.5 and 3.0 g·kg-1 groups. The mice in EFCL groups were ig given EFCL 1.5 and 3.0 g·kg-1, respectively. Thirty minutes later, wine 12 ml· kg-1 was administered to mice except in normal group. The activity of alanine transaminase （ALT） and aspartate aminotransaminase （AST） was detected in serum, and the level of superoxide dismutase （ SOD）, malondialdehyde （MDA） and glu- tathione （GSH） was tested in the liver tissue with kits 24 h after wine administration. The patholog- ical changes were observed after HE and amylase-periodic acid Schiff （D-PAS） staining, and the NF-KB and a-smooth muscle actin （a-SMA） expression was detected by using immunohistochemical method. RESULTS Compared with normal group, the activities of ALT and AST were increased by 28.0% and 28.9% （ P 〈 0.01 ） in model group ; while SOD and GSH level decreased from 706±46to （515±68）kU·g-1 protein, and （251±61） to （126±18）mg·g-1 protein; MDA content increased from （204±21 ） to （258±50）Ixmol＇g-1 protein （P 〈0.01 ） ; and the expression of NF-KB and a-SMA significantly increased （ P 〈 0.01 ）. Compared with model group, the activity of ALT decreased by 18.3% and 19.8%, and the activity of AST decreased by 6.4% and 9.7% in EFCL 1.5 and 3.0 g＇kg-1 groups （P 〈0.01, P 〈0.05） , respectively; while the levels of SOD and GSHin EFCL 3.0 g＇kg-1 group averagely increased by 61.4% and 14.8% （P〈0.01, P〈 0.05）. Furthermore, the severe hepatic lesions as well as neutrophilic infiltration and ballooning degenerations of hepatocytes induced by ethanol were considerably reduced in EFCL 1. 5 and 3.0 g·kg-1 groups, and the expression of NF-κB and a-SMA was significantly downregulated （P 〈 0.01 ）. CONCLUSION EFCL has protective effect against acute alcohol-induced liver damage, which may be related with its downregurating the expression of NF-KB and inhibiting the proliferation of hepatic satellite cells.
出处
《中国药理学与毒理学杂志》
CAS
CSCD
北大核心
2012年第6期829-834,共6页
Chinese Journal of Pharmacology and Toxicology
基金
广东省科技项目(2010A040200005)
广东省科技项目(2012B040304013)
广东医学院大学生创新实验项目(09ZZF010)~~
关键词
黄皮果
乙醇
肝损伤
抗氧化
NF-ΚB
Α-平滑肌肌动蛋白
Clausena lansium （Lour.） Skeels
ethanol
liver injury
antioxidation
NF-κB
or-smooth muscle actin
作者简介
官堂明（1988-），男，硕士研究生，主要从事药理学研究，Tel：13692395050，E-mail：stmgame@139．com；
通讯作者：李文德，E-mail：gdmcli@yahoo．com．cn，Tel：（0769）2388405
