滨蒿内酯通过抑制matrilin-2的表达防治过量对乙酰氨基酚诱导的小鼠急性肝损伤

Prevention of scoparone on acute liver injury induced by excessive acetaminophen in mice by inhibiting the expression of matrilin-2

目的探讨滨蒿内酯防治过量对乙酰氨基酚(APAP)诱导的小鼠急性肝损伤的作用及其机制。方法30只C57BL/6小鼠按体质量随机分对照组、模型组、N-乙酰-L-半胱氨酸(NAC)组和滨蒿内酯25、50 mg/kg组,每组6只。NAC组和滨蒿内酯组连续ig给药7 d后,ip 300 mg/kg APAP 24 h诱导小鼠建立急性肝损伤模型。收集小鼠血清和肝组织,检测血清中丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、碱性磷酸酶(ALP)水平,检测肝组织中丙二醛(MDA)、超氧化物歧化酶(SOD)和谷胱甘肽(GSH)水平;HE染色观察肝组织病理学变化;TUNEL染色检测肝细胞凋亡情况;Western blotting和RT-qPCR法检测肝组织matrilin-2的蛋白和mRNA表达水平。结果与模型组比较,滨蒿内酯能显著降低APAP诱导小鼠血清ALT、AST和ALP水平,差异有统计学意义(P<0.05);与模型组比较,滨蒿内酯能显著降低肝组织MDA水平,增加肝组织SOD和GSH水平,差异有统计学意义(P<0.05);与模型组比较,滨蒿内酯能显著降低肝组织坏死面积、减少细胞凋亡,降低matrilin-2的蛋白和mRNA表达水平(P<0.05)。结论滨蒿内酯可以改善APAP诱导的小鼠急性肝损伤,其作用机制可能是通过抑制matrilin-2的表达。

Objective To investigate the effect and mechanism of scoparone on acute liver injury induced by excessive acetaminophen(APAP)in mice.Methods Thirty C57BL/6 mice were randomly divided into control group,model group,NAC group,scoparone 25 and 50 mg/kg groups according to their body weight.The acute liver injury model was induced by ip injection of APAP(300 mg/kg)for 24 h in NAC group and scoparone group after 7 d of continuous gavage.The contents of ALT,AST,and ALP in serum,and MDA,SOD and GSH in liver tissue were measured,and the pathological changes of liver tissue was detected with HE staining.The apoptosis of hepatocyte was measured using TUNEL staining,and the mRNA and protein levels of matrilin-2 in liver tissue were detected with RT-qPCR and Western blotting.Results Compared with model group,scoparone could significantly reduce the serum ALT,AST,and ALP levels of mice induced by APAP,with a statistically significant difference(P<0.05).Compared with the model group,scoparone could significantly reduce the MDA content of liver tissue,but increase the SOD and GSH levels of liver tissue,with a statistically significant difference(P<0.05).Compared with the model group,scoparone could significantly reduce the necrosis and apoptosis of liver tissue,and the protein and mRNA expression levels of matrilin-2 was significantly decreased(P<0.05).Conclusion Scoparone can ameliorate the acute liver injury induced by APAP in mice,and its mechanism may be through inhibiting the expression of matrilin-2.