泮托拉唑对肝硬化门静脉高压大鼠RhoA/ROCK通路及胃黏膜微循环的影响  

Effects of Pantoprazole on RhoA/ROCK Pathway and Gastric Mucosal Microcirculation in Rats with Liver Cirrhosis Portal Hypertension

作　　者：米琛[1] 李培杰[1] 马富权 李伟之[1] Mi Chen;Li Peijie;Ma Fuquan;Li Weizhi(Department of Gastroenterology,the First Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710061,China)

机构地区：[1]西安交通大学第一附属医院消化内科,西安710061

出　　处：《中国药师》2021年第7期218-222,共5页China Pharmacist

基　　金：陕西省重点研发计划项目(编号:2018SF-051)。

摘　　要：目的:探讨泮托拉唑对肝硬化门静脉高压(PHT)大鼠Ras同源基因家族成员A/Rho相关激酶(RhoA/ROCK)通路及胃黏膜微循环的影响。方法:橄榄油和40%四氯化碳(CCl4)混合液注射,并同时猪油、胆固醇饲养建立肝硬化PTH大鼠模型,模型成功大鼠随机分为3组:模型组、泮托拉唑组(静脉滴注0.8 mg·kg^(-1)泮托拉唑)、泮托拉唑+U-46619组(静脉滴注0.8mg·kg^(-1)泮托拉唑+1.5 pg·kg^(-1)U-46619),同时设置对照组(静脉滴注等体积生理盐水),每日1次,连续5 d。右颈动脉插管检测门静脉压力(PVP)、平均动脉压(MAP)、心率(HR);全自动生化仪检测肝功能指标天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、白蛋白(Alb)、球蛋白(GLO)、总蛋白(TP)水平,并计算AST/ALT、白蛋白/球蛋白(A/G);苏木精-伊红(HE)检测肝组织、胃黏膜组织形态学变化;蛋白免疫印迹(WB)检测胃黏膜组织RhoA、ROCK、血管紧张素Ⅱ(AngⅡ)、内皮素-1(ET-1)蛋白水平。结果:模型组肝细胞多数空泡增大、肝细胞脂变、坏死严重,胃黏膜微绒毛损伤严重,细胞间稀疏,核收缩、深染,炎症浸润;泮托拉唑组肝细胞空泡症状不明显,胃黏膜微绒毛损伤得以缓解;泮托拉唑+U-46619组肝细胞脂变、坏死,胃黏膜微绒毛损伤相较于泮托拉唑组严重,细胞间隔变大、细胞核收缩、深染严重。与对照组相比,模型组PVP、HR,静脉血中AST、ALT、GLO水平,胃黏膜组织中RhoA、ROCK、AngⅡ、ET-1蛋白水平升高,MAP、AST/ALT、Alb、A/G水平降低(P<0.05);与模型组相比,泮托拉唑组PVP、HR,静脉血中AST、ALT、GLO水平,胃黏膜组织中RhoA、ROCK、AngⅡ、ET-1蛋白水平降低,MAP、AST/ALT、Alb、A/G水平升高(P<0.05);与泮托拉唑组相比,泮托拉唑+U-46619组PVP、HR,静脉血中AST、ALT、GLO水平,胃黏膜组织中RhoA、ROCK、AngⅡ、ET-1蛋白水平升高,MAP、AST/ALT、Alb、A/G水平降低(P<0.05)。结论:泮托拉唑在肝硬化PHT中可以通过抑制RhoAObjective:To investigate the effects of pantoprazole on Ras homolog gene family,member A/Rho-associated kinase(RhoA/ROCK)pathway and gastric mucosal microcirculation in liver cirrhosis portal hypertension(PHT)rats.Methods:The liver cirrhosis PTH rat model was established by injecting olive oil and 40%carbon tetrachloride(CCl4)mixture and feeding with lard and cholesterol,and the rats were randomly divided into three groups:model group,pantoprazole group(intravenous drip of 0.8 mg·kg^(-1) pantoprazole),pantoprazole+U-46619 group(intravenous drip of 0.8 mg·kg^(-1) pantoprazole+1.5 pg·kg^(-1) U-46619),at the same time,the control group was set up(intravenous drip of equal volume of normal saline),once a day,for 5 consecutive days.Portal vein pressure(PVP),mean arterial pressure(MAP)and heart rate(HR)were measured by right carotid artery catheterization;the levels of aspartate aminotransferase(AST),alanine aminotransferase(ALT),albumin(Alb),globulin(GLO)and total protein(TP)were detected by an automatic biochemical analyzer,and AST/ALT and albumin/globulin(A/G)were calculated;hematoxylin eosin(HE)was used to detect the morphological changes of liver tissue and gastric mucosa;Western blot(WB)was used to detect the protein levels of RhoA,ROCK,angiotensinⅡ(AngⅡ)and endothelin-1(ET-1)in gastric mucosa.Results:In the model group,most of the hepatocytes were vacuoles with fatty degeneration and serious necrosis,and microvilli of gastric mucosa were seriously damaged with sparse intercellular space,contracting nuclear,deep staining and inflammatory infiltration;in pantoprazole group,the vacuoles of hepatocytes were not obvious,and the damage of gastric microvilli was alleviated;in pantoprazole+U-46619 group,hepatocytes became fat and necrotic,the gastric microvilli injury was more serious than that of pantoprazole group,the intercellular septum became larger,the nucleus contracted and hyperchromatic.Compared with those in the control group,the PVP,HR,levels of AST,ALT and GLO in venous blood,protein levels of RhoA,RO

关 键 词：泮托拉唑 肝硬化门静脉高压 Ras同源基因家族成员A/Rho相关激酶通路 胃黏膜微循环 

分 类 号：R965.1[医药卫生—药理学]