己酮可可碱灌胃对大鼠酒精性肝炎的治疗作用及其机制探讨

Therapeutic effect and mechanism of pentoxifylline on rats with alcoholic hepatitis

目的 观察己酮可可碱(PTX)灌胃对大鼠酒精性肝炎(AH)的治疗作用,并探讨其机制。方法 将30只Wistar雄性大鼠随机分为A、B、C组各10只,A、B组每日灌胃梯度酒精制备AH模型,A组于第9周始每日予9mg/(kg·d)的PTX,B、C组予等量生理盐水,连续4周。比较各组大鼠一般情况及血清ALT、AST和肝脏组织变化、过氧化物酶体增殖物受体α(PPAR-α)、核因子κBP65(NF-κBP65)蛋白相对表达量。结果 C组大鼠行为敏捷,食欲好,毛发光滑,有光泽,大便性状正常;B组初始期出现醉酒症状,2~4h后逐渐好转,4周后出现酒精耐受情况,9周时出现毛发脱落、不喜吃食、大便为稀便,12周末更为严重;A组前9周表现与B组相同,9周后逐步出现食欲较前增加,大便成型,掉毛现象较前好转,体质量缓慢增长。与C组比较,A组和B组初始、4周体质量升高,8、12周体质量降低(P均<0.05);与B组比较,A组初始~12周体质量升高(P均<0.05)。与C组比较,A、B组血清ALT、AST水平升高(P均<0.05);与B组比较,A组血清ALT、AST水平降低(P均<0.05)。肉眼观:C组肝脏质地细腻,色泽红润,无黄色颗粒附着,无淤血;B组肝脏质脆,易碎,色泽暗红,且外表部分附有黄色油腻颗粒,肝淤血较重;A组仅有极少数肝脏有黄色颗粒附着,淤血情况较实验组轻。镜下观:C组无肝损伤;B组有肝脏损伤,且肝脏损伤程度最重;A组有肝脏损伤,但损伤程度较B组轻。与C组比较,A、B组PPAR-α蛋白相对表达量降低,NF-κBP65蛋白相对表达量升高(P均<0.05);与B组比较,A组PPAR-α蛋白相对表达量升高,NF-κBP65蛋白相对表达量降低(P均<0.05)。结论 PTX可一定程度减轻大鼠肝脏损害,机制可能与上调PPAR-α表达和下调NF-κBP65表达有关。

Objective To observe the therapeutic effect of pentoxifylline (PTX) on alcoholic hepatitis (AH) rats and to explore its mechanism. Methods Thirty Wistar male rats were randomly divided into groups A, B, and C. The rats in the groups A and B were daily administrated gradient alcohol to prepare AH models;rats in the group A were treated with 9 mg/(kg·d) alcohol daily from week 9, while rats in the groups B and C with the same amount of normal saline for 4 weeks. The relative expression levels of serum ALT, AST and liver tissue change, peroxisome proliferator receptor-α(PPAR-α) and nuclear factor κB P65 (NF-κB P65) protein were compared between the groups. Results The rats in the group C were agile, with good appetite, smooth hair, shiny and normal stool characteristics. The symptoms of drunkenness occurred in the initial stage of group B, gradually improved after 2 to 4 h, and alcohol tolerance occurred after 4 and 9 weeks.When the hair fell off, the rats did not like eating, and the stool was loose, which was more serious at 12 weeks. In the first 9 weeks, group A showed the same performance as group B. After 9 weeks, the appetite gradually increased, the stool was formed, and the hair loss was earlier. What′s more, the body quality was slowly growing. Compared with the group C, the initial and 4-week body weights of group A and group B increased, and the body weight decreased at 8 weeks and 12 weeks (all P <0.05). Compared with the group B, the body mass from initial to 12 weeks increased in the group A ( P <0.05). Compared with the group C, the serum ALT and AST levels in the group A and group B increased (all P <0.05). Compared with the group B, the serum ALT and AST levels in the group A decreased (both P <0.05). The naked eye view: in the group C, the liver texture was fine, the color was rosy, with no yellow particles adhesion, and no congestion;in the group B, liver was brittle, dark red color, and the surface was accompanied by yellow greasy particles, hepatic congestion was heavier;in the group A, very few livers with yellow particles attached, and the congestion was lighter. Microscopic view: There was no liver injury in the group C;liver damage occurred in the group B, and liver damage was the most serious;group A had liver damage, but the degree of injury was lighter than that of group B. Compared with group C, the relative expression of PPAR-α protein in the groups A and B decreased, and the relative expression of NF-κB P65 protein increased (all P <0.05). Compared with the group B, the relative expression of PPAR-α protein in the group A increased, and the relative expression of NF-κB P65 protein decreased (both P <0.05). Conclusion PTX can alleviate the liver damage of rats to some extent, which may be related to the up-regulation of PPAR-α expression and down-regulation of NF-κB P65 expression.