沉默ZKSCAN3基因表达加重脂多糖诱导的小鼠肺损伤  

Silencing ZKSCAN3 gene expression aggravates lung injury induced by LPS in mice

作　　者：张蕾[1] 肖兴鹏[1] 丁煌 ZHANG Lei;XIAO Xingpeng;DING Huang(Department of Anesthesiology,Renmin Hospital of Wuhan University,Wuhan 430061,Hubei,China)

机构地区：[1]武汉大学人民医院麻醉科,湖北武汉430061

出　　处：《中国临床药理学与治疗学》2023年第2期164-170,共7页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：湖北省自然科学基金面上项目资助(2020CFB705)。

摘　　要：目的:拟使用脂多糖(LPS)诱导小鼠肺损伤模型探讨ZKSCAN3在急性肺损伤(ALI)中的作用。方法:验证ZKSCAN3 siRNA效能后,32只雄性C57BL/6小鼠,随机分为4组(n=8):对照组、LPS组、无意义siRNA组和ZKSCAN3 siRNA组。对照组及LPS组小鼠经尾静脉给予PBS 1 mL;无意义siRNA组小鼠经尾静脉给予相应剂量包含无意义siRNA的PBS;而ZKSCAN3 siRNA组小鼠给予相应剂量包含ZKSCAN3 siRNA(50μg)的无RNA酶的PBS。24 h后LPS组、无意义siRNA组、ZKSCAN3 siRNA组小鼠经气管插管滴入LPS溶液(5 mg/kg)制造急性肺损伤(ALI)模型;对照组经气管插管给予相应剂量的PBS(20μL)。建模给药24 h后取材检测。结果:与LPS组比较,沉默ZKSCAN3基因表达进一步导致SOD活性和Bcl-2水平降低;而MDA、Bax及caspase-3增高;与此相应的是BAL中蛋白质和细胞的含量、肺组织细胞凋亡率及病理学评分显著升高(P<0.05)。结论:沉默ZKSCAN3基因表达加重了LPS导致的肺组织损伤,它可能与通过削弱肺组织的抗氧化功能及加剧组织坏死从而加重小鼠肺组织的病理损伤。AIM:To explore the role of ZKSCAN3 in acute lung injury(ALI)induced by lipopolysaccharide(LPS).METHODS:After verifying the efficacy of ZKSCAN3 siRNA,male C57BL/6 mice were randomly divided into 4 groups(n=8):control group(group A),LPS group(group B),scrambled siRNA group(group C)and ZKSCAN3 siRNA group(group D).Mice in groups A and B were given 1 mL of PBS via tail vein;mice in groups C were given corresponding doses of PBS containing scrambled siRNA;and mice in group D were given corresponding doses of RNase-free PBS containing ZKSCAN3 siRNA(50μg).After 24 hours,mice in groups B,C,and D were instilled with LPS solution(5 mg/kg)through tracheal intubation to create an ALI model;group A was given the corresponding dose of PBS(20μL).The samples were collected and tested 24 hours after the modeling administration.RESULTS:Compared with group B,silencing ZKSCAN3 gene expression reduced SOD activity and Bcl-2 level;while MDA,Bax and caspase-3 increased;correspondingly,the content of protein and cells in BAL,the apoptosis rate of lung tissue and the pathological score significantly increased(P<0.05).CONCLUSION:Silencing ZKSCAN3 gene expression aggravates the lung injury caused by LPS,which may aggravate the pathological damage of lung tissue in mice by weakening the antioxidant function and aggravating tissue necrosis.

关 键 词：ZKSCAN3 脂多糖 急性肺损伤 SIRNA 

分 类 号：R965.2[医药卫生—药理学]