尼克酰胺对急性肝功能衰竭小鼠的保护作用

Protective Effect of Nicotinamide on Acute Hepatic Failure in Mice

背景:急性肝功能衰竭(AHF)是多种肝脏疾病发展至终末期的共同病理生理过程,病因复杂、诊断困难、死亡率高。目的:研究尼克酰胺在AHF小鼠中的保护作用。方法:腹腔注射D-半乳糖胺700 mg/kg和脂多糖10μg/kg建立小鼠AHF模型。将54只小鼠分为空白对照组、尼克酰胺对照组、AHF模型组、尼克酰胺低、中、高剂量组(400、800、1 000 mg/kg),检测ALT、AST、TNF-α和IL-6水平,HE染色观察肝组织病理学变化,TUNEL法检测肝细胞凋亡情况,蛋白质印迹法检测肝组织Caspase-3蛋白表达。将另外40只小鼠分为AHF模型组、0.9%Na Cl溶液组以及尼克酰胺低、中、高剂量组,动态观察72 h内的小鼠死亡率。结果:与空白对照组和尼克酰胺对照组相比,AHF模型组ALT、AST水平显著升高(P<0.05),炎性细胞浸润和细胞坏死明显,TNF-α和IL-6水平明显升高(P<0.05),肝细胞凋亡和Caspase-3蛋白表达明显升高(P<0.05);以低、中、高剂量尼克酰胺预处理后,上述指标均明显改善(P<0.05),且呈剂量依赖性。尼克酰胺低、中、高剂量组小鼠生存率分别为37.5%、62.5%、100%,均显著高于AHF模型组(P均<0.05)。结论:尼克酰胺通过抑制炎症反应和肝细胞凋亡而对AHF小鼠有明显的保护作用,并可提高小鼠生存率。

Background：Acute hepatic failure（ AHF）is a common pathophysiological process of end-stage liver disease with complex etiology,difficulty in diagnosis and high mortality rate. Aims：To investigate the protective effect of nicotinamide on AHF in mice. Methods：AHF model in mice was established by intraperitoneal injection with D-galactosamine 700 mg/kg and lipopolysaccharide 10 μg/kg. Fifty-four mice were divided into blank control group,nicotinamide control group, AHF model group and low,moderate,high dose（400,800,1 000 mg/kg）nicotinamide groups,levels of ALT,AST, TNF-α and IL-6 were determined,HE staining was used to examine hepatic histological injury,liver cell apoptosis was measured by TUNEL assay,and protein expression of Caspase-3 was detected by Western blotting. Another 40 mice were divided into AHF model group,saline group and low,moderate,high dose（400,800,1 000 mg/kg）nicotinamide groups,mortality rate was observed dynamically. Results：Compared with blank control group and nicotinamide control group,levels of ALT and AST were significantly increased（P〈0. 05）,infiltration of inflammatory cells and necrosis of cells and levels of TNF-α and IL-6 were significantly increased（ P 〈0. 05 ）,and apoptosis of liver cells and protein expression of Caspase-3 were significantly increased in AHF model group（P 〈0. 05）. In groups pretreated with low, moderate and high dose nicotinamide,all the above-mentioned indices were significantly improved in a dose-dependent manner（P〈0. 05）. Survival rate in low,moderate,high dose nicotinamide groups was significantly higher than that in AHF model group（37. 5%,62. 5%,100% vs. 0%,P all 〈0. 05）. Conclusions：Nicotinamide could protect mice from AHF via inhibiting inflammatory response and hepatocyte apoptosis,thereby increase the survival rate.