首页|PM2.5对代谢相关脂肪性肝病模型小鼠肝淋巴生成的影响

PM2.5对代谢相关脂肪性肝病模型小鼠肝淋巴生成的影响

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目的 研究大气细颗粒物(particulate matter 2.5,PM2.5)暴露对C57BL/6J小鼠和代谢相关脂肪性肝病模型小鼠肝淋巴生成的影响,为防治PM2.5暴露所致肝损伤提供新靶点.方法 将40只雄性C57BL/6J小鼠随机分为正常组,PM2.5组,代谢相关脂肪性肝病模型组(MAFLD组)和PM2.5-MAFLD组.MAFLD组和PM2.5-MAFLD组小鼠连续12周给予高脂饲料,其余两组给予普通饲料.从13~16周,PM2.5组和PM2.5-MAFLD组小鼠通过气管滴注法进行PM2.5染毒(每周2次);其余两组小鼠同时通过气管滴注法滴注生理盐水.末次PM2.5染毒结束24 h后将实验动物处死.测定小鼠血清丙氨酸氨基转移酶(alanine aminotransferase,ALT)和天冬氨酸氨基转移酸(aspartate aminotransferase,AST)水平;用免疫荧光染色法评估肝淋巴LYVE1表达水平;测定肝氧化应激指标(4-HNE和T-GSH/GSSG)水平;用蛋白免疫印迹法测定肝淋巴生成标志蛋白(PROX1和LYVE1),淋巴生成调节蛋白VEGF-C和淋巴连接蛋白VE-cadherin的蛋白质表达水平.结果 PM2.5染毒显著增加了 MAFLD组小鼠血清AST和ALT水平,显著降低了肝组织PROX1、LYVE1和VEGF-C蛋白表达水平,增加肝4-HNE水平和降低了肝T-GSH/GSSG水平(P<0.05).然而,PM2.5染毒并没有显著影响C57BL/6J小鼠血清AST和ALT水平、肝组织中 PROX1、LYVE1、VEGF-C 和 VE-cadherin 的蛋白表达水平及肝的 4-HNE 和 T-GSH/GSSG(P>0.05).结论 PM2.5染毒能显著加重MAFLD小鼠肝的氧化损伤,并且能通过降低肝VEGF-C减少肝淋巴生成.
Effect of particulate matter 2.5 on hepatic lymphangiogenesis in metabolic-associated fatty liver disease model mice
Objective To study the effect of fine particulate matter(particulate matter 2.5,PM2.5)exposure on hepatic lymphangiogenesis in C57BL/6J mice and metabolic-associated fatty liver disease(MAFLD)model mice,and to provide a novel target for prevention and treatment of PM2.5-induced liver injury.Methods Forty male C57BL/6J mice were randomly divided into a control group,PM2.5 group,MAFLD group,and PM2.5-MAFLD group.Mice in the MAFLD and PM2.5-MAFLD groups were fed high-fat diet for 12 weeks,and mice in the other groups were fed normal chow diet.From weeks 13 to 16,mice in the PM2.5 and PM2.5-MAFLD groups were exposed to PM2.5 by tracheal instillation(twice per week),and mice in the other groups were instilled with saline at the same time.All animals were euthanized 24 h after the last PM2.5 instillation.Serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were measured,and the expression of LYVE1 in liver tissues was visualized using immunofluorescence staining.Hepatic oxidative stress markers levels(4-HNE and GSH/GSSG)were measured.The protein expression levels of lymphangiogenesis markers(PROX1 and LYVE1),lymphangiogenesis regulatory protein VEGF-C,and the lymphatic junctional function marker VE-cadherin in liver tissue were determined using Western Blot.Results PM2.5 exposure significantly increased the levels of serum AST and ALT,markedly decreased the protein expression of PROX1 and LYVE1,increased the protein expression of VEGF-C and VE-cadherin in the liver,increased the level of 4-HNE,and decreased the T-GSH/GSSG ratio in livers of mice in the MAFLD group(P<0.05).However,PM2.5 exposure did not affect the levels of serum AST and ALT,protein expression of PROX1,LYVE1,or VEGF-C;level of 4-HNE;or T-GSH/GSSG ratio in the livers of the C57BL/6J mice(P>0.05).Conclusions PM2.5 exposure obviously aggravated hepatic oxidative injury and reduced hepatic lymphangiogenesis by reducing the VEGF-C concentration in the livers of MAFLD model mice.

particulate matter 2.5metabolic-associated fatty liver diseaseoxidative stresslymphangiogenesis

丁世彬、李洋、陈玉萍、蒋金金

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江苏医药职业学院公共卫生与管理学院,江苏盐城 224005

江苏医药职业学院科技处,江苏盐城 224005

PM2.5 代谢相关脂肪性肝病 氧化应激 淋巴生成

国家自然科学基金项目江苏省自然科学基金青年基金项目江苏高校"青蓝工程"资助项目江苏高校"青蓝工程"资助项目江苏省卫生健康委员会医学科研项目

82204095BK202101412023-272024-14M2022035

2024

中国实验动物学报
中国实验动物学会,中国医学科学院医学实验动物研究所

中国实验动物学报

CSTPCD北大核心
影响因子:0.767
ISSN:1005-4847
年,卷(期):2024.32(8)