海兔素对酒精性肝损伤大鼠Fas/FasL及TNF-α表达的影响

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目的观察海兔素(Aplysin)对酒精性肝损伤大鼠肝组织Fas、FasL表达及血清肿瘤坏死因子-α(TNF-α)水平的影响。方法50只雄性Wistar大鼠随机分为5组。正常对照组,每日灌胃生理盐水1次;酒精模型组,每日给予50%乙醇8mL/(kg·bw·d)灌胃,2周后把50%乙醇剂量递增为12mL/(kg·bw·d),继续灌胃4周;海兔素低、中、高剂量组,每日分别给予Aplysin 50、100、150mg/(kg·bw·d)灌胃,酒精剂量同模型组。实验进行了6周。末次灌胃12h后,大鼠称重后给予7%水合氯醛麻醉,腹主动脉取血,留取肝组织,计算肝指数;HE染色观察肝脏组织的病理学改变;免疫组化法检测肝组织中Fas、FasL表达情况,计算其阳性表达率;并采用酶联免疫吸附法(ELISA)检测血清中TNF-α的浓度。结果与正常对照组相比,酒精模型组大鼠肝指数明显增加(P<0.05);与酒精模型组相比,海兔素中、高剂量组大鼠肝指数均显著降低(P<0.05)。HE染色病理观察结果显示,酒精模型组大鼠肝小叶结构模糊,胞质中可见大小不等、数量不一的圆形脂肪空泡,可见炎性细胞浸润;海兔素各剂量组肝小叶结构有不同程度破坏,与酒精模型组相比较,肝细胞坏死程度明显减轻。酒精模型组与正常对照组相比Fas/FasL表达明显增多,且血清TNF-α含量明显升高(P<0.05);海兔素各剂量组Fas/FasL表达以及血清中TNF-α含量均低于酒精模型组,差异有显著性(P<0.05);随着海兔素摄入剂量的增加Fas表达相应减少且成剂量依赖性(P<0.05)。结论海兔素可改善因酒精暴露引起的肝损伤,其机制可能与通过减少肝组织Fas、FasL表达、降低血清TNF-α水平从而抑制肝细胞的凋亡有关。 Objective To observe the effect of Aplysin on the expression of Fas and FasL in liver tissue and serum level of tumor necrosis factor-α (TNF-α) in rats with alcoholic liver injury. Methods Fifty male Wistar rats were randomly divided into five groups. The rats in the normal control group were fed with normal saline once a day. Alcohol model group was orally given 8% ethanol (8mL / (kg · bw · d)) daily for 2 weeks, and 50% ethanol was increased to 12mL / (kg · bw · d) for 4 weeks. The rabbits in the low, medium and high dose groups were given Aplysin 50, 100, 150 mg / (kg · bw · d) orally daily with the same dosage as the model group. The experiment was conducted for 6 weeks. The rats were weighed and then given 7% chloral hydrate for anesthesia, abdominal aorta blood was taken, liver tissues were taken out, liver index was calculated, the pathological changes of liver tissues were observed by HE staining, and liver tissues were detected by immunohistochemistry The expression of Fas and FasL in the tissue was calculated and the positive expression rate was calculated. The concentration of TNF-α in the serum was detected by enzyme linked immunosorbent assay (ELISA). Results Compared with the normal control group, the liver index of alcohol model group was significantly increased (P <0.05). Compared with the alcohol model group, the liver index of the medium and high dose Havena group was significantly decreased (P <0.05) . The results of HE staining showed that the structure of hepatic lobule in alcohol model group was obscure, and the number of round fat vacuoles with varying sizes was seen in the cytoplasm. Inflammatory cell infiltration was observed in each group; Have different degrees of damage, compared with the alcohol model group, liver necrosis significantly reduced. Compared with the normal control group, the expression of Fas / FasL in alcohol model group increased significantly, and the level of serum TNF-αincreased significantly (P <0.05). The expression of Fas / FasL in each dose group and the level of TNF-αin serum In alcohol group, the difference was significant (P <0.05). With the increase of rabbits, the expression of Fas decreased in a dose-dependent manner (P <0.05). Conclusions Hyposptor can improve hepatic injury induced by alcohol exposure, and its mechanism may be related to the inhibition of hepatocyte apoptosis by reducing the expression of Fas and FasL in liver tissue and decreasing the level of serum TNF-α.
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