槲皮黄酮对酒精性肝损伤大鼠的治疗研究

Impacts of Quercetin on Alcoholic Liver Injury in Rats

目的探讨槲皮黄酮对酒精性肝损伤大鼠的治疗效果及其作用机制。方法将30只大鼠随机分为正常对照组、模型组、低剂量槲皮黄酮治疗组、中剂量槲皮黄酮治疗组、高剂量槲皮黄酮治疗组,每组6只大鼠。用酒精+0.5ml鱼油灌胃诱导酒精性肝损伤模型,治疗组分别给予40、80、160mg/kg槲皮黄酮灌胃治疗,6周后处死大鼠,观察各组大鼠间肝脏病理变化,测定血清转氨酶(ALT)及血浆内毒素水平,采用ELISA试剂盒测定细胞因子TNF-α、IL-6、IL-18含量,并利用Western blot法检测大鼠肝组织CD14、LBP、TNF-α、IL-1、IL-18蛋白表达水平。结果相对正常对照组而言,组织切片检测发现模型大鼠出现肝细胞脂肪变性、点状坏死、伴随炎性细胞浸润,血清ALT、TNF-α、IL-1、IL-18及血浆内毒素含量显著升高(P均<0.05),并且肝组织中CD14、LBP、TNF-α、IL-1、IL-18蛋白表达水平明显上升(P均<0.05);槲皮黄酮治疗后发现肝损伤大鼠肝细胞脂肪变性仍存在,但点状坏死和炎性细胞浸润消失,血液中TNF-α、IL-1、IL-18及内毒素含量明显降低(P均<0.05),并且肝组织中CD14、LBP、TNF-α、IL-1、IL-18蛋白表达水平显著降低(P均<0.05)。结论槲皮黄酮可以缓解酒精性肝损伤大鼠肝脏的炎症和坏死,其作用机制与降低内毒素水平、抑制库普弗细胞活化和下调促炎细胞因子表达有关。

Objective To study the impacts of quercetin on alcohol - stimulated liver injury in rats. Methods Thirty Sprague - Dawley rats were randomly divided into control, model, quercetin treatment （40mg/kg,80mg/kg, 160mg/kg） groups. Ethanol plus 0.5ml fish oil were used to induce alcoholic liver injury for 6 weeks. Liver injury was evaluated using pathological examination and serum ALT levels. The plasma endotoxin and serum TNF-α, IL- 1 and IL- 18 levels were analyzed by ELISA method. The expression of CD14, LBP, TNF - α, IL - 1 and IL - 18 proteins in the liver were measured by Western blot. Results The increased serum ALT, fatty degen- eration, focal necrosis and inflammatory cell infiltration in the liver were investigated in model group. In addition, plasma endotoxin, ser- um TNF - α, IL - 1, IL - 18 levels, and the expression levels of CD14, LBP, TNF -α, IL - 1, and IL - 18 proteins significantly elevat- ed in model group compared with control group （ P 〈 0.05 ）. However, quercetin treatment improved histological changes, and significant- ly reduced the levels of plasma endotoxin and serum TNF-α, IL- 1, IL- 18, as well as the expression of CD14, LBP, TNF- a, IL- 1 and IL- 18 proteins （P all 〈 0.05）. Fatty degeneration was still investigated in quercetin treatment group, but focal necrosis and in- flammatory cell infiltration disappeared. Conclusion Quercetin can protect liver against necrosis and inflammation induced by alcohol, and the mechanism may involve its effect on the reduction of plasma endotoxia, and inhibition of Kupffer cell activity and proinflammatory cytokine expression.