姜黄素衍生物对四氯化碳诱导肝纤维化的治疗作用

Efficacy of the Gurc-OEG on rat liver fibrosis induced by CCl_4

目的:探讨姜黄素衍生物(Curc-OEG)对四氯化碳诱导肝纤维化的治疗效果。方法:以四氯化碳诱导形成大鼠肝实质损伤性肝纤维化模型。大鼠分为正常对照组(A组)、模型组(B组)、低剂量组(C组)、中剂量组(D组)、高剂量组(E组)、秋水仙碱组(F组)。除A组外,各组给予四氯化碳和橄榄油混合液皮下注射,2次/周,4周后B组给予生理盐水尾静脉注射,C、D、E组分别给予25、50、100mg.kg-1.d-1的Curc-OEG尾静脉注射,F组给予0.1mg.kg-1.d-1秋水仙碱灌胃。10周后测定肝功能及肝组织羟脯氨酸(Hyp)含量;做肝脏HE和天狼星红染色;定量PCR法测金属蛋白酶抑制因子-1(TIMP-1)、金属蛋白酶-13(MMP-13)基因的表达,Western Blot法测CollagenⅠ蛋白的表达。结果:与模型组比较,中、高剂量组ALT、AST明显降低(P<0.05),羟脯氨酸及CollagenⅠ蛋白表达明显降低(P<0.05),MMP-13 mRNA明显上调(P<0.05),以及TIMP-1 mRNA明显下调(P<0.05),并且HE及天狼星红染色结果也观察到肝脏炎症及纤维化程度明显减轻。结论:Curc-OEG能减轻四氯化碳诱导的大鼠肝纤维化。

AIM. To evaluate the efficacy of Curc-OEG in preventing CC14-induced hepatic fibrosis and to study the effects of that on expression of MMP-13 mRNA, TIMP-1 mRNA and Collagen I. METHODS： Liver fibrosis in rats was induced by CC14. Rats were assigned into control group（A）, model group （B）, low-dose group（C）, medium-dose group（D）, high-dose group（E） and colchicin group（F）. All rats ex- cept those in group A were given subcutaneous injection of CCIa and olive oil mixture, twice a week for 10 weeks. After 4 weeks, those in group B were treated with normal saline by intravenous injection, those in group C, D and E were treated with Curc-OEG for 25, 50, 100 mg · kg ^-1·d^-1 by intravenous injection, those in group F were treated with colchicin for 0.1 mg· kg ^-1·d^-1 by gavage as positive control. At the end of the tenth week, the serum levels of AI.T, AST and cotent of hydroxyproline in ho- mogenate were determined. The extent of liver inflammation and fibrosis was evaluated with HE and Sirus staining. The expressions of MMP-13,TIMP-1 and CollagenI were observed with RT PCR and Western Blot respectively.RESULTS： Compared with model group, medium and high dose of curcumin derivative could obviously decrease the content of hydroxyproline in liver tissue（P〈C0.05） and levels of ALT, AST in serum（P〈0.05） and expression of Collagen I （P〈0.05）, and it also reduced inflammation destruction of liver architecture and collagen accumulation. Further study showed thai MMP 13 mRNA was up-regulated（P〈0.05） and TIMP-1 mRNA was down-regulated （ P 〈2 0.05） after Curc （）EG treatment. CONCLUSION： Curc -OEG could ameliorate the progress of liver fibrosis in duced by CCl4.