急性肝衰竭大鼠肝星状细胞内质网应激调节HGF表达实验研究  

The HGF expression regulated by endoplasmic reticulum stress of hepatic stellate cells in the rats with acute liver failure

作　　者：蓝远强[1] 吴发胜[2] 黄丽珍 梁敏 LAN Yuan-qiang;WU Fa-sheng;HUANG Li-zhen;LIANG Min(Department of Internal Medicine,Wuxiang Hospital of Nanning Second People′s Hospital,530000;Department of Cancer radiotherapy,Ruikang Hospital Affiliated to Guangxi University of traditional Chinese Medicine,530000)

机构地区：[1]南宁市第二人民医院五象医院内一科,广西南宁530000 [2]广西中医药大学附属瑞康医院肿瘤放疗科

出　　处：《肝脏》2021年第5期538-541,共4页Chinese Hepatology

基　　金：广西自然科学基金项目(2013GXNSFBA019171)。

摘　　要：目的研究内质网应激(ERS)调节急性肝衰竭(ALF)大鼠肝星状细胞肝细胞生长因子(HGF)表达的作用机制。方法60只清洁级SD大鼠作为实验动物,采用随机数字表法将60只大鼠分为A、B、C三组,每组20只。三组大鼠均利用D-氨基半乳糖(D-GaIN)与脂多糖(LPS)构建ALF大鼠模型。A、C两组大鼠在建模术后1 h给予0.6 mL/kg衣霉素干预,C组大鼠在完成上述操作后再腹腔注射4-苯基丁酸钠(4-PBA)500 mg/kg。B组大鼠为阴性对照组,未行特殊干预。在ALF建模术后0 h(T1)、2 h(T2)、8 h(T3)及12 h(T4)时,每组分别处死5只大鼠,留取血清和肝组织标本,检测大鼠血清HGF水平,采用荧光定量聚合酶链式反应(RT-PCR)检测三组大鼠肝组织HGF mRNA的相对表达量。结果A组T2、T3及T4时血清HGF分别为(63.9±7.0)ng/mL、(54.8±9.5)ng/mL及(42.0±6.7)ng/mL,显著低于B组[(82.3±10.6)ng/mL、(78.6±8.3)ng/mL及(76.2±9.0)ng/mL,P<0.05]和C组[(74.7±8.3)ng/mL、(70.4±10.2)ng/mL及(67.8±7.7)ng/mL,P<0.05]。B组和C组T2、T3及T4时血清HGF水平差异有统计学意义(P<0.05)。A组T2、T3及T4时肝组织HGF mRNA相对表达量为2.9±0.5、2.5±0.8及1.7±0.4,显著低于B组(4.6±0.7、4.7±0.9及4.4±0.7,P<0.05)和C组(3.8±0.6、3.5±0.7及3.1±0.8,P<0.05)。B组和C组T2、T3及T4时肝组织HGF mRNA相对表达量差异有统计学意义(P<0.05)。结论ERS对ALF大鼠肝星状细胞HGF表达具有调节作用,进而参与ALF病理进程。Objective To study the mechanism of endoplasmic reticulum stress(ERS)regulating the expression of hepatocyte growth factor(HGF)in hepatic stellate cells of rats with acute liver failure(ALF).Methods 60 clean SD rats were used as experimental animals.The 60 rats were divided into A,B and C groups by random number table,with 20 rats in each group.The three groups of rats were treated with D-galactosamine(D-GaIN)and lipopolysaccharide(LPS)to build ALF model.The rats in group A and C were treated with 0.6 mL·kg-1 of tunicamycin one hour after modeling operation.The rats of group C were immediately intraperitoneally injected with 4-phenyl butyric acid(4-PBA)500 mg·kg-1 after completing the above operation.The rats in group B were negative control group without special intervention.There were 5 rats in each group,which were killed at 0 hour(T1),2 hours(T2),8 hours(T3)and 12 hours after ALF modeling(T4),the serum and liver tissue samples were collected,the serum HGF level in rats were measured.The expression of HGF in liver tissue of three groups of rats were detected by real-time-polymerase chain reaction(RT-PCR).Results The serum HGF of T2,T3 and T4 were(63.9±7.0)ng/mL,(54.8±9.5)ng/mL and(42.0±6.7)ng/mL,respectively,which were significantly lower than group B[(82.3±10.6)ng/mL,(78.6±8.3)ng/mL and(76.2±9.0),P<0.05]and group C[(74.7±8.3)ng/mL,(70.4±10.2)ng/mL and(67.8±7.7)ng/mL,P<0.05].There were significant difference in serum HGF level between group B and group C at T2,T3 and T4(P<0.05).The relative expression of HGF mRNA in T2,T3 and T4 of group A were(2.9±0.5),(2.5±0.8)and(1.7±0.4),which were significantly lower than those of group B[(4.6±0.7),(4.7±0.9)and(4.4±0.7),P<0.05]and group C[(3.8±0.6),(3.5±0.7)and(3.1±0.8),P<0.05].There were significant difference of HGF mRNA expression between group B and group C at T2,T3 and T4(P<0.05).Conclusion The endoplasmic reticulum stress(ERS)can regulate the expression of HGF in hepatic stellate cells of ALF rat and participate in the pathological process of ALF

关 键 词：内质网应激 急性肝衰竭 肝星状细胞 HGF 

分 类 号：R73[医药卫生—肿瘤]