目的 探討濱蒿內(nèi)酯防治過量對乙酰氨基酚（APAP）誘導(dǎo)的小鼠急性肝損傷的作用及其機制。方法 30只C57BL/6小鼠按體質(zhì)量隨機分對照組、模型組、N-乙酰-L-半胱氨酸（NAC）組和濱蒿內(nèi)酯25、50 mg/kg組，每組6只。NAC組和濱蒿內(nèi)酯組連續(xù)ig給藥7 d后，ip 300 mg/kg APAP 24 h誘導(dǎo)小鼠建立急性肝損傷模型。收集小鼠血清和肝組織，檢測血清中丙氨酸氨基轉(zhuǎn)移酶（ALT）、天冬氨酸氨基轉(zhuǎn)移酶（AST）、堿性磷酸酶（ALP）水平，檢測肝組織中丙二醛（MDA）、超氧化物歧化酶（SOD）和谷胱甘肽（GSH）水平；HE染色觀察肝組織病理學(xué)變化；TUNEL染色檢測肝細(xì)胞凋亡情況；Western blotting和RT-qPCR法檢測肝組織matrilin-2的蛋白和mRNA表達(dá)水平。結(jié)果 與模型組比較，濱蒿內(nèi)酯能顯著降低APAP誘導(dǎo)小鼠血清ALT、AST和ALP水平，差異有統(tǒng)計學(xué)意義（P<0.05）；與模型組比較，濱蒿內(nèi)酯能顯著降低肝組織MDA水平，增加肝組織SOD和GSH水平，差異有統(tǒng)計學(xué)意義（P<0.05）；與模型組比較，濱蒿內(nèi)酯能顯著降低肝組織壞死面積、減少細(xì)胞凋亡，降低matrilin-2的蛋白和mRNA表達(dá)水平（P<0.05）。結(jié)論 濱蒿內(nèi)酯可以改善APAP誘導(dǎo)的小鼠急性肝損傷，其作用機制可能是通過抑制matrilin-2的表達(dá)。

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.

R965

河南省醫(yī)學(xué)科技攻關(guān)計劃聯(lián)合共建項目（LHGJ20190224）