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400mg·kg^-1·d^-灌胃治疗,姜黄素衍生物组给予姜黄素衍生物100mg·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-timePCR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、(383.0±75.6)U/L、(406.3±204.7)U/L、(107.0±73.7)U/L;AST水平分别为:(137.7±32.7)U/L、(585.3±36.7)U/L、(485.0±246.5)U/L、(202.7±56.0)U/L,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);显著降低肝组织中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。
Aim To investigate the effects of anti-in- flammation and antioxidation of an amphiphilic curcumin 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 subcutaneous injection of CCl4 and olive oil mixture,twice a week for 8weeks. After 4 weeks,rats of control and model group were treated with normal saline intravenously,curcumin group were administered with curcumin 400mg·kg^-1·d^-by gavage and CurcOEG group were treated with Curc-OEG 100mg·kg^-1·d^-intravenously 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-k B,IL-1β,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,( 107. 0 ± 73. 7) U·L- 1respectively; that of AST was( 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^- 1respectively,Curc-OEG possessed more hepatoprotective effects than that of curcumin. Liver pathology showed Curc-OEG treatment could significantly alleviate steatosis,reduce inflammation 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-1β,IL-6,TNF-α,COX-2( P 〈0. 05). Moreover,Curc-OEG reduced the level of MOD and increased the levels of SOD and GSH. Conclusion Curc-OEG could more significantly protect the rat liver from CCl4-caused fibrogenesis by anti-inflammatory and antioxidant effect than curcumin.