UⅡ/UT系统对急性肝衰竭小鼠肝组织Ces1f基因表达的影响  

Effect of UⅡ/UT System on the Expression of Carboxylesterase1 f Gene in Liver Tissue of Mice with Acute Liver Failure

作　　者：杨婉花[1,2] 娄晓丽[1,2] 杨雪[1,2] 王学敏 刘亮明 YANG Wanhua;LOU Xiaoli;YANG Xue;WANG Xuemin;LIU Liangming(Department of Infectious Diseases,Shanghai Songjiang Clinical Medical College of Nanjing Medical University,Shanghai,201600,China;Songjiartg Branch of first People’s Hospital Affiliated to Shanghai Jiaotong University,Shanghai,201600,China)

机构地区：[1]南京医科大学上海松江临床医学院,上海市201600 [2]上海交通大学医学院附属松江医院感染科,上海市201600

出　　处：《医学分子生物学杂志》2020年第6期409-415,共7页Journal of Medical Molecular Biology

基　　金：国家自然科学基金(No.8177012,81070357,30660066)。

摘　　要：目的探讨urotensinⅡ(U)/T(UⅡreceptor)系统对急性肝衰竭小鼠肝内Ces1f基因表达的影响。方法24只健康雄性Balb/c小鼠随机分为4组(6只/组)。A组:健康对照组;B组:预处理对照组;C组:急性肝衰竭(acute liver failure,ALF)模型组;D组:预处理ALF模型组。ALF模型组和预处理ALF模型组以脂多糖(lipopolysaccharide,LPS)50 pg/k g联合D-半乳糖胺(D-galactosamin,D-GalN)800 mg/kg腹腔注射诱导ALF,健康对照组注射等体积的0.9%氯化钠溶液;预处理ALF组在造模前30 min给予0.6 mg/kg Urantide尾静脉注射;预处理对照组同样预处理后腹腔注射相同体积的0.9%氯化钠溶液。造模6 h后,收集小鼠血清和肝组织标本。肝损伤程度采用血清ALT、AST和肝组织HE染色分析;肝组织UU和Ces1f表达采用实时荧光定量PCR(reatime-PCR)方法检测。结果LPS/D-GalN攻击后,肝内UII mRNA的表达在2 h即显著升高,6 h达峰值,随后逐渐下降,至12 h水平接近正常值。而肝Ces1f mR-NA的表达在2 h和4 h时与正常水平无明显统计学差异,在6 h则显著下调,至10 h水平达最低值,12 h表达水平有所回升;LPS/D-GalN攻击6 h后(即C组)血清ALT、AST显著升高、肝内见大片坏死性炎性损伤病变,D组ALT、AST水平较C组明显降低,且肝组织内损伤程度较C组有明显改善;A、B、C、D组肝组织UⅡmRNA相对表达量分别为(1.00±0.00)、(1.08±0.33)、(9.62±2.31)、(5.61±1.3)。其中,C、D组水平较A和B组高,而D组较C组低,均有显著性差异(P<0.05);A、B、C、D组肝组织Ces1f mRNA的相对表达量分别为(1.00±0.00)、(0.91±0.31)、(0.44±0.12)、(1.14±0.40)。其中,C组水平较A、B、D组均低(P<O.O 1),D组水平较C组高(P<0.01),具有显著性差异。结论ALF小鼠肝内Ces1f基因表达显著下调,且其下调可能与UⅡ基因表达信号系统激活调控有关。Objective To investigate the effect of urotensin lege of hepatic carboxylesterase1 f(Ces1f)expression in mice suffering from acute liver failure(ALF).Methods A total of 24 male Balh/c mice were randomly divided into four groups:the healthy control group(group A);pretreatment control group(group B),ALF model group(group C)and pretreatment ALF group(group D).For modeling,in ALF model group and pretreatment ALF group,mice were intraperitoneally injected lipopolysaccharide(LPS)at 50 μg/kg in combination with D-galactosamine(DGA LN)at 800 mg/kg.The control mice were injected an equal volume of 0.9% sodium chloride solution.Fhe pretreatment ALF mice were given a 0.6 mg/kg urantide via tail vein injection 30 min before modeling.In the pretreatment control group,mice were given an equal volume of 0.9% sodium chloride solution.And then the liver specimens and serum were collected 6 h after modeling.The degree of liver injury was evaluated in terms of HE staining of liver tissues and the levels of serum ALT and AST.The levels of hepatic Ceslf mRNA were detected by real time PCR.Results After stimulation with LPS/D-GalN,the expression of UⅡmRNA in the liver was increased significantly at 2 h,reaching a peak at 6 h,and then gradually decreased until the level was close to normal at 12 h.However,the expression of liver Ces1f mRNA was not significantly different from the normal level at 2 h and 4 h,but was significantly down-regulated at 6 h,reaching the lowest level at 10 h,and then rose at 12 h.Serum ALT and AST in group C increased significantly 6 h after LPS/D-GalN stimulation.A large number of necrotizing inflammatory lesions were found in the liver.The level of serum ALT and AST was lower in group D than in group C.The hepatic injury in group D was significantly improved as compared with group C.The relative expression of UⅡ mRNA in liver tissues in groups A,B,C,and D was 1.00±0.00,1.08±0.33,9.62±2.31,5.61±1.3,respectively.Among them,the level was higher in groups C and D than in groups A and B,while the level w

关 键 词：急性肝衰竭 UⅡ/UT系统 Ces1f基因 小鼠 

分 类 号：R575.3[医药卫生—消化系统]