首页|组蛋白去乙酰化酶抑制剂SAHA对慢性间歇性低氧小鼠肝损伤的影响及其机制

组蛋白去乙酰化酶抑制剂SAHA对慢性间歇性低氧小鼠肝损伤的影响及其机制

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目的 探索组蛋白去乙酰化酶抑制剂SAHA对凋亡蛋白Caspase-9/Caspase-3的表达和慢性间歇性低氧小鼠肝损伤的影响及其机制.方法 将雄性C57小鼠随机分为正常组(control组)、慢性间歇性低氧组(CIH组)和SAHA干预组(CIH+SAHA组),将CIH+SAHA组与CIH组小鼠放入低氧仓内进行间歇性低氧处理,每天8h,持续4周,从第3周起,每日造模前给予实验小鼠腹腔注射SAHA 50mg/(kg·d),给药持续2周.实验第4周后,测量小鼠体质量,然后处死小鼠,HE染色观察肝组织形态学变化,测定血清中谷丙转氨酶(ALT)和谷草转氨酶(AST)水平,Western blot检测小鼠肝组织中裂解型胱天蛋白酶3(c-Caspase-3)和Caspase-9的蛋白水平,TUNEL试剂盒检测小鼠肝组织细胞凋亡情况.结果 与contro l组相比,间歇性低氧4周后,CIH组小鼠肝指数显著升高且肝组织损伤明显,肝组织细胞凋亡相关蛋白Caspase-9和c-Caspase-3的表达水平显著增高,肝组织细胞凋亡比例增加(P<0.05);与CIH组相比,CIH+SAHA组肝指数、ALT、AST水平以及Caspase-9和c-Caspase-3蛋白表达水平、肝组织细胞凋亡指标降低(P<0.05).结论 SAHA可能通过抑制凋亡相关蛋白Caspase-9/Caspase-3,进而改善慢性间歇性低氧引起的小鼠肝损伤.
Effect and mechanism of histone deacetylase inhibitor SAHA on liver injury in chronic intermittent hypoxia mice
Objective To explore the effect and its mechanism of histone deacetylase inhibitor SAHA on the expression of apoptotic protein Caspase-9/Caspase-3 and the liver injury in chronic intermittent hypoxia mice.Methods Male C57 mice were randomly divided into normal group(control group),chronic intermittent hypoxia group(CIH group)and CIH+SAHA group.The mice in CIH+SAHA group and CIH group were treated with 8 h intermittent hypoxia every day in hypoxia chamber for four weeks.Starting from the 3rd week,the experimental mice were intraperitoneally injected with 50 mg/(kg·d)SAHA every day before the intermittent hypoxia for two weeks.After the 4th week of the experiment,the weight of mice was recorded,and then the mice were killed to observe the liver histopathological changes by HE staining,and detect the levels of ALT and AST in serum.Western blot was used to detect the protein levels of c-Caspase-3 and Caspase-9 in mouse liver tissue,and TUNEL was used to detect the cell apoptosis in mouse liver tissue.Results Compared with control group,liver index and liver tissue injury were significantly increased after 4 weeks of intermittent hypoxia in CIH group,the damage of liver tissues was found,and the expression levels of Caspase-9 and c-Caspase-3 proteins,and the cell apoptosis in liver tissue were significantly increased(P<0.05).Compared with CIH group,liver index,ALT,AST,Caspase-9 and c-Caspase-3 protein expression levels and apoptosis index of liver tissue were decreased in CIH+SAHA group(P<0.05).Conclusion SAHA may ameliorate the liver injury induced by chronic intermittent hypoxia in mice by inhibiting apoptosis-related protein Caspase-9/Caspase-3.

histone deacetylase inhibitorchronic intermittent hypoxialiver injuryapoptosis-related proteinsapoptosis

汪金丽、金宇、孙敏琼、余孝海

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安徽城市管理职业学院公共管理教研室,合肥 230011

安徽医科大学机能学实验中心

组蛋白去乙酰化酶抑制剂 慢性间歇性低氧 肝损伤 凋亡相关蛋白 细胞凋亡

安徽省高等学校科研项目安徽省研究生教育质量工程项目安徽医科大学国家级创新创业训练计划

2022AH0523932022xscx053202310366037

2024

山西医科大学学报
山西医科大学

山西医科大学学报

CSTPCD
影响因子:0.931
ISSN:1007-6611
年,卷(期):2024.55(2)
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