氢生理盐水对对乙酰氨基酚致小鼠急性肝损伤的保护作用

Protective effect of hydrogen-rich saline against acetaminophen-induced liver injury in mice

目的观察氢生理盐水对对乙酰氨基酚致小鼠急性肝损伤的保护作用。方法 30只雄性BALB/C小鼠随机分成3组:对照组、模型组和治疗组,每组10只。治疗组和模型组同时给予对乙酰氨基酚500 mg/kg腹腔内注射诱发小鼠急性肝损伤,1 h后治疗组每3 h腹腔注射氢生理盐水6 m L/kg,模型组给予相同剂量的生理盐水;对照组各时间点均腹腔注射相同剂量的生理盐水。所有动物在给予对乙酰氨基酚后24 h处死,测定血浆谷丙转氨酶(ALT)、谷草转氨酶(AST)、肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)水平,以及肝组织匀浆丙二醛(MDA)和还原型谷胱甘肽(GSH)含量,TUNEL法检测肝细胞凋亡指数,观察肝组织病理学改变和肝细胞坏死程度。结果氢生理盐水能显著降低对乙酰氨基酚致小鼠急性肝损伤的血浆ALT[(816.3±300.2)U/L vs(3 933.0±1 112.0)U/L,P<0.01]、AST[(403.8±83.6)U/L vs(2851.0±992.9)U/L,P<0.01]水平,显著抑制炎症因子TNF-α[(3.54±0.42)pg/m L vs(6.58±0.72)pg/m L,P<0.01]、IL-6[(350.20±66.67)pg/m L vs(553.10±67.73)pg/m L,P<0.05]的生成和MDA[(5.89±0.81)nmol/m L vs(8.26±0.60)nmol/m L,P<0.05]的含量,并增加GSH[(362.8±37.9)μg/m L vs(230.8±53.1)μg/m L,P<0.05]储备,明显降低肝细胞凋亡指数[(5.67%±2.28%)vs(1.93%±0.82%),P<0.01],显著改善肝组织病理学变化和降低肝细胞坏死的严重程度[(2.9±0.74)vs(1.7±0.82),P<0.01]。结论氢生理盐水对对乙酰氨基酚致小鼠急性肝损伤具有明显的保护作用。

objective To investigate the protective effect of hydrogen-rich saline（HS） against acetaminophen-induced liver injury in mice. Methods Thirty BALB/C male mice were randomly divided into three groups： control group, model group, and treatment group, each group contained 10 mice. In the treatment group and model group, liver injury was induced by acetaminophen（i.p. 500 mg/kg）. One hour after the administration of acetaminophen, HS（6 m L/kg） or an equivalent volume of NS was given intraperitoneally every 3 h. The control group was injected with the same dose of normal saline at the corresponding time point. All animals were killed at 24 h after the administration of acetaminophen, the levels of plasma alanine aminotransferase（ALT）, asparate aminotransferase（AST）, tumor necrosis factor alpha（TNF-α）, interleukin-6（IL-6）, the contents of malondialdehyde（MDA） and glutathione（GSH） in the liver tissue were measured; the hepatocellular apoptosis index was detected by TUNEL method; the pathological change of liver tissue and the necrosis area of hepatic cell were observed. Results In the acetaminophen-induced liver injury in mice, HS could significantly reduce the levels of plasma ALT [（816.3±300.2） U/L vs（3 933.0±1 112.0） U/L, P〈0.01] and AST [（403.8±83.6） U/L vs（2 851.0±992.9） U/L, P〈0.01], inhibit the generation of inflammatory factors TNF-α [（3.54±0.42） pg/m L vs（6.58±0.72） pg/m L, P〈0.01] and IL-6 [（350.20±66.67） pg/m L vs（553.10±67.73） pg/m L, P〈0.05], and decrease the content of the MDA [（5.89±0.81） nmol/m L vs（8.26±0.60） nmol/m L, P〈0.05] and increase the reservation of GSH [（362.8±37.9）μg/m L vs（230.8±53.1） μg/m L, P〈0.05]. In addition, HS could markedly decrease the hepatocellular apoptosis index [（5.67±2.28）% vs（1.93±0.82）%, P〈0.01], ameliorate the liver histopathology and diminish the degree of hepatocyte necrosis [（2.9±0.74） vs（1.7±0.82）, P〈0.01]. Conclusion The hydrogen-rich saline has a protective role against acetaminophen-induced liver injury in mice.