荔枝核总黄酮对肝纤维化大鼠肝细胞Bcl-2/Bax表达的影响

Effect of total flavone of Litchi chinensis Sonn on the expression of Bcl-2 and Bax in hepatic fibrosis in rats

目的:研究荔枝核总黄酮(total flavone from Litchi Chinensis Sonn,TFL)对二甲基亚硝胺(dimethylnitrosamine,DMN)肝纤维化大鼠肝细胞凋亡的影响及作用机制.腔注射制备大鼠肝纤维化模型,造模的同时,TFL干预组分别以高、低剂量的TFL灌胃6wk进行干预治疗,空白对照组、秋水仙碱组分别以生理盐水、秋水仙碱灌胃作为阴阳性对照.HE及Masson染色观察肝纤维化程度;免疫组织化学二步法检测Bcl-2、Bax的表达;测定血清ALT、AST的水平.结果:模型组大鼠肝组织中Bcl-2、Bax的表达较正常组显著升高(P=0.000),TFL高、低剂量给药组及秋水仙碱组Bcl-2的表达较模型组升高(P=0.000,0.047,0.021),Bax的表达较模型组降低(P=0.000,0.014,0.007),TFL高剂量组与低剂量组比较Bcl-2的表达升高(P=0.018),Bax的表达显著降低(P=0.002).Bcl-2、Bax在秋水仙碱组与TFL低剂量组中的表达无显著性差异(P=0.726,0.767).肝纤维化严重程度与Bax的表达显著正相关(P=0.000);与Bcl-2的表达负相关(P=0.000).空白对照组、TFL高低剂量给药组及秋水仙碱组血清ALT、AST均明显低于模型组,具有显著性差异(P=0.000).低剂量组与秋水仙碱组无显著性差异(P=0.597,0.669).结论:TFL具有较好的抗肝纤维化和改善肝功能的作用,并推测这种作用可能与上调Bcl-2、下调Bax的表达,抑制肝细胞的凋亡有关.

AIM： To study the effect of total flavone of Litchi chinensis Sonn （TFL） on liver cell apoptosis in rats with hepatic fibrosis and to explore possible mechanisms involved. METHODS： Fifty rats were randomly divided into five groups： blank control group, colchicine group, model group, low- and high-dose TFL groups. Hepatic fibrosis was induced in rats by intraperitoneal injection of dimethylnitrosamine. The TFL groups were intragastrically administered with different doses of TFL for 6 wk, while the blank control group and colchicine group were given normal saline and colchicine, respectively. After treatment, liver samples were taken to examine the degree of liver fibrosis by HE and Masson staining and to detect Bcl-2 and Bax expression by immunohistochemistry. Serum ALT and AST levels were also measured. RESULTS： The expression of Bcl-2 and Bax in the model group was significantly higher than that in the normal group （both P = 0.000）. The expression of Bcl-2 was higher and that of Bax was lower in the TFL groups and colchicine group than in the model group （Bcl-2： P = 0.000, 0.047, 0.021; Bax： P = 0.000, 0.014, 0.007）, and in the high-dose TFL group than in the low-dose TFL group （P = 0.018, 0.002）. Bcl-2 and Bax expression showed no significant difference between the low-dose TFL group and colchicine group （P = 0.726, 0.767）. The severity of liver fibrosis was positively correlated with Bax expression （P = 0.000） but negatively with Bcl-2 expression （P = 0.000）. Serum levels of ALT and AST were significantly lower in the blank control group, TFL groups and colchicine group than in the model group （all P = 0.000）, but showed no significant difference between the low-dose TFL group and colchicine group （P = 0.597, 0.669）. CONCLUSION： TFL can resist hepatic fibrosis and improve liver function possibly by up-regulating Bcl-2 expression and down-regulating Bax expression to inhibit liver cell apoptosis.