CAJ | 학술논문

目的：探讨新型双亲姜黄素衍生物（curc-OEG）对四氯化碳（CCl4）诱导大鼠肝纤维化的抗炎抗氧化作用。方法大鼠分为正常组、模型组、姜黄素组和姜黄素衍生物组。除正常组外，其余各组给予 CCl4混合液皮下注射，每周2次。造模4周后，正常组、模型组给与尾静脉注射生理盐水，姜黄素组给予姜黄素400 mg·kg －1·d －1灌胃治疗，姜黄素衍生物组给予姜黄素衍生物100 mg·kg －1·d －1尾静脉注射。治疗4周后分别取血清及肝组织标本。血清检测 ALT、AST 水平；肝组织做病理学检查，Real-time PCR 法检测相关炎症因子的 mRNA 表达水平，试剂盒检测丙二醛（MDA）、超氧化物歧化酶（SOD）、谷胱甘肽（GSH）水平。结果正常组、模型组、姜黄素组和姜黄素衍生物组 ALT 水平分别为：（31.7±8.7）U ·L －1、（383.0±75.6）U ·L －1、（406.3±204.7）U·L －1、（107.0±73.7）U·L －1；AST 水平分别为：（137.7±32.7）U·L －1、（585.3±36.7）U·L －1、（485.0±246.5）U·L －1、（202.7±56.0）U·L －1，姜黄素衍生物较姜黄素显示出更好的护肝降酶作用（P ＜0.05）。肝脏病理切片显示姜黄素衍生物较姜黄素具有更明显的延缓肝脏脂肪变性、减轻炎症细胞浸润及抗肝纤维化的作用。与姜黄素比较，姜黄素衍生物明显下调炎症相关因子 NF-κB、IL-1β、IL-6、TNF-α、COX-2mRNA 及蛋白表达水平（P ＜0.05）；明显降低肝组织中 MDA 水平，提高 GSH 、SOD 表达水平，增强抗氧化能力。结论姜黄素衍生物较传统姜黄素具有更好的抗炎、抗氧化作用，能够有效地延缓四氯化碳诱导的肝纤维化进程。
목적：탐토신형쌍친강황소연생물（curc-OEG）대사록화탄（CCl4）유도대서간섬유화적항염항양화작용。방법대서분위정상조、모형조、강황소조화강황소연생물조。제정상조외，기여각조급여 CCl4혼합액피하주사，매주2차。조모4주후，정상조、모형조급여미정맥주사생리염수，강황소조급여강황소400 mg·kg －1·d －1관위치료，강황소연생물조급여강황소연생물100 mg·kg －1·d －1미정맥주사。치료4주후분별취혈청급간조직표본。혈청검측 ALT、AST 수평；간조직주병이학검사，Real-time PCR 법검측상관염증인자적 mRNA 표체수평，시제합검측병이철（MDA）、초양화물기화매（SOD）、곡광감태（GSH）수평。결과정상조、모형조、강황소조화강황소연생물조 ALT 수평분별위：（31.7±8.7）U ·L －1、（383.0±75.6）U ·L －1、（406.3±204.7）U·L －1、（107.0±73.7）U·L －1；AST 수평분별위：（137.7±32.7）U·L －1、（585.3±36.7）U·L －1、（485.0±246.5）U·L －1、（202.7±56.0）U·L －1，강황소연생물교강황소현시출경호적호간강매작용（P ＜0.05）。간장병리절편현시강황소연생물교강황소구유경명현적연완간장지방변성、감경염증세포침윤급항간섬유화적작용。여강황소비교，강황소연생물명현하조염증상관인자 NF-κB、IL-1β、IL-6、TNF-α、COX-2mRNA 급단백표체수평（P ＜0.05）；명현강저간조직중 MDA 수평，제고 GSH 、SOD 표체수평，증강항양화능력。결론강황소연생물교전통강황소구유경호적항염、항양화작용，능구유효지연완사록화탄유도적간섬유화진정。
Aim To investigate the effects of anti-in-flammation and antioxidation of an amphiphilic curcu-min derivative (Curc-OEG)on CCl4-induced hepatic fibrosis in rats.Methods Rats were randomly divided into four groups:control group,model group,curcumin and Curc-OEG treatment group.All rats except those in control group were given subcuta-neous injection of CCl4 and olive oil mixture,twice a week for 8 weeks.After 4 weeks,rats of control and model group were trea-ted with normal saline intravenously,curcumin group were ad-ministered with curcumin 400 mg.kg -1 .d -1 by gavage and Curc-OEG group were treated with Curc-OEG 1 00 mg.kg -1 .d -1 intra-venously respectively.After 4 weeks treatment,the serum levels of ALT and AST were tested.HE and Sirus staining were used to evaluate the extent of liver inflammation and fibrosis.The mRNA expression levels of proinflammatory cytokines of NF-kB,IL-1 β, IL-6,TNF-α,COX-2 were observed with Real Time PCR.The level of MOD,SOD and GSH in liver of rats were quantified. Results The levels of ALT in control,model,curcumin and Curc-OEG group was (31 .7 ±8.7)U·L -1 ,(383.0 ±75.6) U·L -1 ,(406.3 ±204.7)U·L -1 ,(1 07.0 ±73.7)U·L -1 respectively;that of AST was (1 37.7 ±32.7)U·L -1 ,(585.3 ±36.7)U·L -1 ,(485.0 ±246.5)U·L -1 ,(202.7 ±56.0) U·L -1 respectively,Curc-OEG possessed more hepatoprotective effects than that of curcumin.Liver pathology showed Curc-OEG treatment could significantly alleviate steatosis,reduce inflamma-tion and apparently suppress hepatic fibrogenesis by reducing the thickness of bridging fibrotic septa.Compared with curcumin, Curc-OEG down-regulated mRNA and protein expression levels of NF-kB,IL-1 β,IL-6,TNF-α,COX-2 (P <0.05 ).Moreo-ver,Curc-OEG reduced the level of MOD and increased the lev-els of SOD and GSH.Conclusion Curc-OEG could more sig-nificantly protect the rat liver from CCl4-caused fibrogenesis by anti-inflammatory and antioxidant effect than curcumin.