Urantide对动脉粥样硬化大鼠肝功能及组织形态学的影响
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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 D3(VD3)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 urotensinⅡ(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.
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 D3(VD3)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 urotensinⅡ(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.
引文
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[9]赵娟.尾加压素II及其与动脉粥样硬化关系的研究进展[J].山东医药,2011,51(23):115-116.
[10]Sun HY,Zhang L,Shen D.Urantide protects CCl4-induced liver injury via inhibiting GPR14 signal in mice[J].Biotechnol Biotechnol Equip,2017,31(1):156-161.
[11]Singh R,Rai U.Immunomodulatory role of urotensins in teleost Channa punctatus[J].Gen Comp Endocrinol,2011,170(3):613-621.
[12]陶蕾,纪立伟,王艳春.他汀类药物对动脉粥样硬化的疗效研究[J].中国现代医学杂志,2017,27(14):93-98.
[13]杨红霞,蒋恒波.他汀类药物对老年颈动脉粥样硬化斑块的影响和对急性心脑血管事件的干预作用[J].临床合理用药,2018,11(1A):78-80.
[14]陈步宽.他汀类药物致肝损伤临床特点及影响因素分析[J].肝脏,2017,22(10):885-903.
[2]刘晓娟,周玉娟,任明.荷丹片对动脉粥样硬化大鼠血清ALT、AST及肝形态学的影响[J].医学研究与教育,2011,28(3):12-15.
[3]Zhao J,Yu QX,Kong W,et al.The urotensin II receptor antagonist,urantide,protects against atherosclerosis in rats[J].Exp Ther Med,2013,5(6):1765-1769.
[4]Brancaccio D,Limatola A,Campiglia P,et al.Urantide conformation and interaction with the urotensin-II receptor[J].Arch Pharm(Weinheim),2014,347(3):185-192.
[5]赵娟,王佳昕,李雪燕,等.Urantide对实验性动脉粥样硬化大鼠胸主动脉损伤的影响[J].吉林大学学报,2013,39(4):653-656.
[6]魏国华,刘兰,蔡晓波,等.高脂饮食组所致动脉粥样硬化家兔肝组织学损伤评估[J].中国动脉硬化杂志,2008,16(5):373-375.
[7]Seto WK,Yuen MF.Nonalcoholic fatty liver disease in Asia:emerging perspectives[J].J Gastroenterol,2017,52(2):164-174.
[8]许新,辛永宁,宣世英.非酒精性脂肪性肝病与动脉粥样硬化关联性的研究进展[J].中国肝脏病杂志,2015,7(3):42-45.
[9]赵娟.尾加压素II及其与动脉粥样硬化关系的研究进展[J].山东医药,2011,51(23):115-116.
[10]Sun HY,Zhang L,Shen D.Urantide protects CCl4-induced liver injury via inhibiting GPR14 signal in mice[J].Biotechnol Biotechnol Equip,2017,31(1):156-161.
[11]Singh R,Rai U.Immunomodulatory role of urotensins in teleost Channa punctatus[J].Gen Comp Endocrinol,2011,170(3):613-621.
[12]陶蕾,纪立伟,王艳春.他汀类药物对动脉粥样硬化的疗效研究[J].中国现代医学杂志,2017,27(14):93-98.
[13]杨红霞,蒋恒波.他汀类药物对老年颈动脉粥样硬化斑块的影响和对急性心脑血管事件的干预作用[J].临床合理用药,2018,11(1A):78-80.
[14]陈步宽.他汀类药物致肝损伤临床特点及影响因素分析[J].肝脏,2017,22(10):885-903.