原花青素在对乙酰氨基酚诱导的急性肝损伤中的保护作用及机制

Protective effect and mechanism of procyanidin in acute liver injury induced by acetaminophen

摘要:

目的：研究原花青素在对乙酰氨基酚诱导的急性肝损伤中的保护作用及机制。方法：将昆明种小鼠随机分为6组，每组8只。分别为 PBS 正常对照组、对乙酰氨基酚（acetaminophen，APAP）模型组、原花青素（100 mg/kg）药物对照组和原花青素药物预处理组（低剂量[10 mg/kg]，中剂量[50 mg/kg]和高剂量组[100 mg/kg]）。检测各组小鼠血清丙氨酸氨基转移酶（alanine aminotransferase，ALT）、天门冬氨酸氨基转移酶（aspartate aminotransferase，AST）和肝匀浆中丙二醛（malondialdehyde，MDA）、超氧化物歧化酶（superoxide dismutase，SOD）的变化，并采用HE染色观察各组病理形态的改变，Western blot法测定各组SOD蛋白的表达。结果：原花青素中、高剂量药物预处理组与APAP模型组比较，ALT（F=555.20，P=0.000）、AST（F=168.51，P=0.000）、MDA（F=155.15，P=0.000）明显降低，SOD（F=291.84，P=0.000）明显升高。病理观察发现，APAP模型组肝组织结构破坏，肝细胞水样变性，中央静脉淤血。原花青素中、高剂量药物预处理组则肝小叶结构清晰，细胞变性轻微，无明显淤血。Western blot结果发现，APAP模型组中SOD蛋白表达被抑制，而原花青素中、高剂量药物预处理组则表达增加。结论：原花青素在对乙酰氨基酚诱导的急性肝损伤中有保护作用，其机制与药物抗氧化应激作用有关。

Abstract:

Objective：To investigate protective effect and mechanism of procyanidin in acute liver injury induced by acetaminophen. Method：The KM mice were randomly divided into six groups（n=8），including PBS control group，acetaminophen model group，pro－cyanidin control group（100 mg/kg） and procyanidin pre-treatment groups including low-dose（10 mg/kg），medium-dose（50 mg/kg） and high-dose groups（100 mg/kg）. The activities of alanine aminotransferase（ALT），aspartate aminotransferase（AST），malondialde－hyde（MDA） in the serum and the concentration of MDA in the liver homogenate of the mice were detected by commercial kits. Mean－while，the pathological changes of the liver were observed by HE staining，and the expression of SOD was determined by Western blot. Results：Compared with those in APAP model group，ALT（F=555.20，P=0.000），AST（F=168.51，P=0.000），MDA（F=155.15，P=0.000） in pre-treatment groups of medium-dose and high-dose of procyanidin were significantly lower，while SOD（F=291.84，P=0.000） was markedly higher. The damaged liver structure，hydropic degeneration and the central venous congestion were observed in the APAP model group，but the liver injuries in pre-treatment groups of medium-dose and high-dose of procyanidin were slighter. Based on the results of Western blot，SOD protein expression in APAP model group was inhibited，while the pre-treatment with medium-dose and high-dose of procyanidin could rescue its expression. Conclusion：Procyanidin has a protective role in acetaminophen-induced acute liver injury，and the preliminary mechanism is related to antioxidative character of drug.