Urantide对动脉粥样硬化大鼠肝功能及组织形态学的影响  

Effect of urantide on liver function and histomorphology in atherosclerotic rats

作　　者：崔海鹏[1] 刘凯[1] 郭天娇 孙晓旭 王途 谢亚芹[1] 李颖[1] 苗光新[1] 赵娟[1] CUI Hai-peng;LIU Kai;GUO Tian-jiao;SUN Xiao-xu;WANG Tu;XIE Ya-qin;LI Ying;MIAO Guang-xin;ZHAO Juan(Department of Pathophysiology,Chengde Medical University,Chengde 067000,China)

机构地区：[1]承德医学院病理生理学教研室,河北承德067000

出　　处：《中国病理生理杂志》2019年第2期218-223,共6页Chinese Journal of Pathophysiology

基　　金：河北省教育厅优秀青年基金资助项目(No.YQ2013005);河北省青年拔尖人才项目;河北省高校重点学科建设项目(冀教高【2013】4号病理学与病理生理学)

摘　　要：目的:探讨urantide对动脉粥样硬化(AS)大鼠肝功能及组织形态学的影响。方法:采用腹腔注射维生素D3(VD3)及高脂饮食的方法复制Wistar大鼠AS模型,随机分为正常对照组、AS模型组、阳性药组和uran-tide组。生化分析仪检测各组大鼠肝功能指标;HE染色观察大鼠胸主动脉和肝脏的病理学变化;RT-qPCR和Western blot法检测大鼠肝脏中尾加压素Ⅱ(UII)及其受体GPR14的mRNA和蛋白表达水平。结果:AS模型组大鼠血清中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、γ-谷氨酰转移酶(γ-GT)、乳酸脱氢酶(LDH)、总胆红素(TBIL)、间接胆红素(IBIL)和碱性磷酸酶(ALP)水平较正常对照组显著升高(P <0.05);urantide组大鼠上述各项指标较模型组均显著降低(P <0.05);各组血清中直接胆红素(DBIL)、总蛋白(TP)、球蛋白(GLB)和白蛋白(ALB)水平均无显著变化。Urantide可延缓AS大鼠肝细胞脂肪变性,修复肝细胞损伤。AS组大鼠肝脏中UII和GPR14mRNA及蛋白表达水平均较正常组显著增高(P <0.05);随着给药时间的延长,urantide治疗组大鼠肝脏中UII和GPR14 mRNA及蛋白表达水平较AS模型组显著降低(P <0.05)。结论:Urantide可明显减轻AS大鼠肝脂肪变性所引起的肝功能损伤。AIM:To investigate the effect of urantide on the liver function and histomorphology in the rats with atherosclerosis(AS).METHODS:The AS Wistar rat model was induced by intraperitoneal injection of vitamin D 3(VD 3)and feeding with high-fat diet.The rats were randomly divided into normal control group,AS model group,positive medicine group and urantide group.The liver function indexes of the rats were measured by biochemical test,and the pathological changes of the aorta and liver of the rats were observed by hematoxylin-eosin(HE)staining.The mRNA expression of urotensin Ⅱ(UII)and GPR14 at mRNA and protein levels in rat livers was determined by RT-qPCR and Western blot.RESULTS:The levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),γ-glutamyltransferase(γ-GT),lactate dehydrogenase(LDH),total bilirubin(TBIL),indirect bilirubin(IBIL)and alkaline phosphatase(ALP)in AS model group were significantly increased compared with normal control group(P<0.05).The above indexes in urantide group were remarkably decreased compared with AS model group(P<0.05).No change of the levels of direct bilirubin(DBIL),total protein(TP),globulin(GLB)and albumin(ALB)in each group was observed.Urantide postponed hepatocyte fatty degeneration and repaired hepatocyte injury in the AS rats.Compared with normal control group,the mRNA and protein levels of UII and GPR14 in the liver were significantly increased in AS model group(P<0.05).With the prolongation of dosing time,the mRNA and protein levels of UII and GPR14 in the liver were significantly decreased in urantide group compared with AS model group(P<0.05).CONCLUSION:Urantide significantly attenuates the liver damage caused by liver fatty degeneration in AS rats.

关 键 词：URANTIDE 动脉粥样硬化 肝功能 尾加压素Ⅱ 脂肪变性 

分 类 号：R543.5[医药卫生—心血管疾病] R363.2[医药卫生—内科学]