β-arrestin2在内毒素诱导的肝脏损伤中的作用  

Effect of β-arrestin2 in endotoxin-induced liver injury

作　　者：蒋梦萍[1] 禤婕滢 徐春[1] 罗千江 尉秀清[1] 

机构地区：[1]中山大学附属第三医院消化内科,广州510630

出　　处：《新医学》2016年第2期84-87,共4页Journal of New Medicine

基　　金：国家自然科学基金项目(81470848)

摘　　要：目的探讨β-arrestin2在内毒素诱导的肝脏损伤中的作用机制。方法建立内毒素诱导的肝脏损伤模型,将β-arrestin2基因敲除型(KO)小鼠20只及同窝β-arrestin2野生型(WT)小鼠20只分别随机分成实验组及对照组(n=10),实验组腹腔内注射脂多糖(5 mg/kg),而对照组注射等量生理盐水,6 h后留小鼠血清和肝脏组织标本。实时定量PCR检测小鼠体内β-arrestin2表达量,ELISA检测各组小鼠血清中ALT、AST及TNF-α水平,蛋白免疫印迹法检测各组β-arrestin2、pp65及p-IкBα蛋白的表达。结果β-arrestin2 WT实验组肝脏组织中β-arrestin2 mRNA为0.18±0.06,明显低于正常对照组的1.00±0.29(t=-4.669,P<0.001),β-arrestin2蛋白表达也明显低于WT对照组;β-arrestin2 KO实验组血清ALT为(204.33±22.33)U/L、AST为(403.40±53.45)U/L,明显高于β-arrestin2 WT实验组ALT的(129.33±9.69)U/L和AST(256.20±40.47)U/L(t=7.55、6.94,P均<0.001)。β-arrestin2 KO实验组血清TNF-α为(155.89±14.89)pg/L,明显高于WT实验组的(101.36±10.65)pg/L(t=9.25,P<0.001)。β-arrestin2 KO实验组肝脏组织中p-IкBα及pp65的蛋白表达量明显高于β-arrestin2 WT实验组。结论β-arrestin2可能通过抑制NF-κB活化、减少TNT-α释放从而减轻内毒素诱导的炎症反应,在内毒素诱导的肝脏损伤中起保护作用。Objective To investigate the mechanism of the function of β-arrestin2 in the endotoxininduced liver injury. Methods Endotoxin-induced liver injury mouse models were established. Twenty β-arrestin2 knockout（ KO） mice and twenty β-arrestin2 wild-type（ WT） littermates were randomly divided into the experimental and control groups（ n = 10）. In the experimental group,liver injury was induced by intraperitoneal injection of 5 mg / kg of lipopolysaccharide,and the control mice were administered with an equivalent quantity of normal saline. Six hours later,serum sampling and liver tissue were collected. The expression of β-arrestin2 in the mouse liver was measured by quantitative real-time PCR. The serum levels of ALT,AST and TNF-α were detected by ELISA. The expression of β-arrestin2,p-p65 and p-IкBα proteins was determined by Western blot. Results The expression level of β-arrestin2 mRNA in the β-arrestin2 WT group was 0. 18 ±0. 06,significantly lower than 1. 00 ± 0. 29 in the control group（ t =- 4. 669,P〈0. 001）. The expression ofβ-arrestin2 protein was also obviously down-regulated. In the β-arrestin2 KO group,the values of ALT and AST were（ 204. 33 ± 22. 33） U / L and（ 403. 40 ± 53. 45） U / L,significantly higher compared with（ 129. 33± 9. 69） U / L and（ 256. 20 ± 40. 47） in the β-arrestin2 WT group（ t = 7. 55,P〈0. 001; t = 6. 94,P〈0. 001）. The serum level of TNF-α in the β-arrestin2 KO group was（ 155. 89 ± 14. 89） pg / L,significantly higher than（ 101. 36 ± 10. 65） pg / L in the β-arrestin2 WT group（ t = 9. 25,P〈0. 001）. In the β-arrestin2 KO group,the expression of p-IкBα and p-p65 proteins within the mouse liver was significantly higher compared with that in the β-arrestin2 WT group. Conclusion β-arrestin2 alleviates endotoxin-induced inflammatory response probably inhibiting the activation of NF-кB and reducing the production of TNF-α,which plays a protective role in endotoxin-induced liver injury.

关 键 词：内毒素诱导的肝脏损伤 β-arrestin2 TLR4/NF-кB/TNF-α信号通路 

分 类 号：R575[医药卫生—消化系统]