机构地区:[1]青岛大学基础医学院免疫学系,山东青岛266071 [2]济宁医学院免疫学与分子医学研究所
出 处:《青岛大学学报(医学版)》2018年第3期268-272,共5页Journal of Qingdao University(Medical Sciences)
基 金:国家自然科学基金资助项目(81671632)
摘 要:目的研究牛蒡子苷元(ATG)对刀豆蛋白A(ConA)诱导的小鼠急性肝炎的保护作用。方法将C57BL/6小鼠随机分成DMSO组、ConA/DMSO组、ConA/ATG组,每组10只小鼠。DMSO组和ConA/DMSO组小鼠腹腔注射DMSO,ConA/ATG组小鼠腹腔注射等体积ATG(30 mg/kg),5h后ConA/DMSO组和ConA/ATG组尾静脉注射ConA(20mg/kg)。12h后处死小鼠,取血清和肝脏组织,用生化分析仪测血清丙氨酸氨基转移酶(ALT)和天门冬氨酸氨基转移酶(AST)水平,苏木精-伊红(HE)染色检测肝组织病理损伤,TUNEL染色检测肝细胞凋亡,ELISA方法检测血清肿瘤坏死因子α(TNF-α)和干扰素-γ(IFN-γ)水平,q-PCR方法检测肝组织中TNF-α和IFN-γmRNA表达水平,流式细胞术检测骨髓来源抑制细胞(MDSCs),生化法检测肝脏匀浆丙二醛(MDA)和髓过氧化物酶(MPO)的表达水平。结果与DMSO组相比,ConA/DMSO组血清ALT和AST水平明显升高(F=125.80、94.74,P<0.05);肝脏组织损伤明显加重;肝细胞凋亡增加;血清和肝组织中TNF-α和IFN-γ水平升高(F=17.52、68.81,P<0.05);肝脏MDSCs募集活化降低;同时MDA和MPO活性升高(F=13.38、14.78,P<0.05)。与ConA/DMSO组比较,ConA/ATG组血清ALT和AST水平明显降低(F=125.80、94.74,P<0.05);肝脏组织损伤明显减轻;肝细胞凋亡减少;血清中TNF-α和IFN-γ的水平降低(F=17.52、68.81,P<0.05);肝组织中TNF-α和IFN-γmRNA的表达水平降低(F=31.55、14.64,P<0.05),MDSCs募集活化明显增强;MDA和MPO活性降低(F=13.38、14.78,P<0.05)。结论 ATG对ConA诱导的小鼠急性肝炎具有明显的保护作用。Objective To investigate the protective effect of arctigenin(ATG)against concanavalin A(ConA)-induced acute hepatitis in mice. Methods C57 BL/6 mice were randomly divided into DMSO group,ConA/DMSO group,and ConA/ATG group,with 10 mice in each group.The mice in the DMSO group and the ConA/DMSO group were given intraperitoneal injection of DMSO,and those in the ConA/ATG group were given intraperitoneal injection of the same volume of ATG(30 mg/kg);5 hlater,the mice in the ConA/DMSO group and the ConA/ATG group were given tail vein injection of ConA(20 mg/kg).The mice were sacrificed 12 hlater,and serum and liver tissue samples were collected.An automatic biochemical analyzer was used to measure the serum levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST);HE staining was used to observe liver pathological injury;TUNEL staining was used to measure cell apoptosis;ELISA was used to measure the serum levels of tumor necrosis factor-α(TNF-α)and interferon gamma(IFN-γ);q-PCR was used to measure the mRNA expression of TNF-αand IFN-γin liver tissue;flow cytometry was used to measure myeloid-derived suppressor cells(MDSCs);and the biochemical method was used to measure the expression of malondialdehyde(MDA)and myeloperoxidase(MPO)in liver homogenate. Results Compared with the DMSO group,the ConA/DMSO group had significant increases in the serum levels of ALT and AST(F=125.80 and 94.74,P〈0.05),significantly greater liver injury,significant increases in hepatocyte apoptosis and the levels of TNF-αand IFN-γin serum and liver tissue(F=17.52 and 68.81,P〈0.05),a significant reduction in recruitment of MDSCs in the liver,and significant increases in the activities of MDA and MPO(F=13.38 and 14.78,P 0.05).Compared with the ConA/DMSO group,the ConA/ATG group had significant reductions in the serum levels of ALT and AST(F=125.80 and 94.74,P〈0.05),significant alleviation of liver injury,a significant reduction in hepatocyte apoptosis,signif
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