敲低剪接因子Prp17对小鼠肝组织形态学和肝功能的影响

Effect of knockdown splicing factor Prp17 on liver morphology and liver function in mice

目的探讨敲低剪接因子Prp17对小鼠肝组织形态学和肝功能的影响。方法构建敲低剪接因子Prp17腺病毒(Ad-shPrp17)。随机将C57BL/6小鼠分为Control组和Ad-shPrp17组,每组8只。Ad-shPrp17组通过内眦静脉注射Ad-shPrp17。10 d后采集小鼠血清和收集肝组织。用苏木精-伊红染色法观察肝组织形态学变化;酶法测定血清谷草转氨酶(AST)和谷丙转氨酶(ALT)活性;荧光定量聚合酶链式反应分析基因表达情况。结果与Control组比较,Ad-shPrp17组小鼠:(1)肝的质量和肝指数显著增加(P<0.01);(2)肝细胞排列散乱,细胞肿胀,胞质疏松化,肝细胞由多角形变成圆形,胞质透明,呈气球样变,部分细胞发生坏死;(3)血清AST和ALT的酶活力显著升高(P<0.01);(4)肝组织TNF-α、IL-1β表达升高(P<0.05)。结论敲低剪接因子Prp17可造成小鼠肝组织形态发生病理改变和肝功能损伤,其机制可能与诱导肝炎症反应有关。这为肝疾病的防治提供新的治疗靶点和理论依据。

Objective To investigate the effects of knockdown splicing factor Prp17 on liver morphology and liver function in mice.Methods The knockdown splicing factor Prp17 adenovirus(Ad-shPrp17)was constructed.C57BL/6 mice were randomly divided into a control group and an Ad-shPrp17 group with 8 mice in each group.The Ad-shPrp17 group was injected with Ad-shPrp17 through medial canthus vein.After 10 days,mouse serum and liver tissue were collected.Pathological changes of liver were observed by hematoxylin-eosin staining.The activities of serum aspartate transaminase(AST)and alanine transaminase(ALT)were determined by enzyme method.Gene expression was analyzed by fluorescence quantitative polymerase chain reaction.Results Compared with the control group,the Ad-shPrp17 group had the following changes:(1)Liver index and the quality of liver significantly increased(P<0.01);(2)with scattered and swollen hepatocytes,loose cytoplasm,the liver cells changed from polygonal to round.The cytoplasm was transparent and ballooning changed,and some cells were necrotic;(3)The enzyme activities of serum ALT and AST were significantly increased(P<0.01);(4)The expression of liver tissue TNF-αand IL1-βincreased(P<0.05).Conclusions Knockdown of splicing factor Prp17 could cause pathological changes and function damage in the liver tissue of mice,and its mechanism may be related to the induction of hepatic inflammatory response.This study provides a new therapeutic target and theoretical basis for the prevention and treatment of liver diseases.