氯膦酸二钠脂质体清除肝内巨噬细胞对CCl4诱导的慢性肝损伤大鼠门脉高压的影响  

Depletion of intrahepatic macrophages by clodronate liposomes in rats with CCl4-induced chronic liver injury and portal hypertension

作　　者：李爽 刘金玉 武晓玉 王宏雅 刘慧萍 赵欣[1] 蔡大勇[1] Li Shuang;Liu Jinyu;Wu Xiaoyu(Institute of Medicinal Plant Development,Chinese Academy of Medical Sciences,Peking Union Medical College,Beijing 100193,China)

机构地区：[1]中国医学科学院北京协和医学院药用植物研究所,北京市100193

出　　处：《实用肝脏病杂志》2020年第4期484-487,共4页Journal of Practical Hepatology

基　　金：国家自然科学基金资助项目(编号:81673674/81903864);中国医学科学院医学与健康科技创新工程项目(编号:2018-I2M-AI-015)。

摘　　要：目的观察氯膦酸二钠脂质体清除肝内巨噬细胞对CCl 4诱导的慢性肝损伤大鼠门脉高压的影响。方法随机将48只Wistar大鼠分为对照组和模型组,每组24只。采用皮下注射橄榄油和四氯化碳(CCl 4)法制备肝损伤模型。在实验d 70,再将每组分为2个亚组,分别经尾静脉注射磷酸盐缓冲液脂质体(PL)或氯膦酸二钠脂质体(CL)处理。在实验d 105,使用BL-420F生理机能实验系统测定大鼠肝脏在体门静脉压力,采用ELISA法检测血sCD163水平,采用免疫组化法检测肝组织CD163和诱导型一氧化氮合酶(iNOS)蛋白表达。结果在对照组内,CL处理大鼠血清sCD163水平为(798.6±61.9)pg/L,显著低于PL处理组[(848.3±26.2)pg/L,P<0.05];在模型组内,CL处理大鼠肝脏指数和门静脉压力分别为(4.7±0.8)和(10.6±2.0)mmHg,显著低于PL处理组[分别为(5.6±1.3)和(12.4±2.7)mmHg,P<0.05];模型组CL处理大鼠血清ALT、AST和sCD163水平分别为(69.9±21.4)U/L、(202.8±14.2)U/L和(980.1±122.3)pg/L,与PL处理大鼠比,均有显著性差异[分别为(97.8±39.6)U/L、(290.6±168.1)U/L和(1083.2±97.2)pg/L,P<0.05];免疫组化结果显示,CL处理大鼠肝组织CD163和iNOS蛋白阳性表达较PL处理大鼠有不同程度的减弱。结论巨噬细胞参与门脉高压的发生和发展。清除巨噬细胞可降低门静脉压力。Objective To study the effect of depletion of intrahepatic macrophages by clodronate liposomes on CCl4-induced portal hypertension in rats.Methods Forty-eight male Wistar rats were randomly divided into two groups with 24 in each,and the rats in the model group were injected with olive oil and carbon tetrachloride(CCl4)twice a week,respectively.At d 70,the rats in the two groups were further divided into two subgroups.The rats in one subgroup were injected with phosphate buffered solution liposomes(PL),and in the other were dealt with clodronate liposomes(CL)intravenously through tail veins once a week to remove intrahepatic macrophages.At d 105,the portal pressure in vivo was measured by BL-420F physiological function experiment system,the serum level of sCD163 was assayed by ELISA,and the positive expression of CD163 and inducible nitric oxide synthase(iNOS)in the liver tissues were detected by immunohistochemistry staining.Results In the control groups,serum level of sCD163 was(798.6±61.9)pg/L in CL injected rats,significantly lower than in the PL injected rats[(848.3±26.2)pg/L,P<0.05];in the model groups,the liver coefficients and portal vein pressure in CL-treated rats were(4.7±0.8)and(10.6±2.0)mmHg,respectively,significantly lower than[(5.6±1.3)and(12.4±2.7)mmHg,P<0.05]in PL-treated rats;serum levels of ALT,AST and sCD163 in CL-treated rats were(69.9±21.4)U/L,(202.8±14.2)U/L and(980.1±122.3)pg/L,respectively,which were significantly lower than[(97.8±39.6)U/L,(290.6±168.1)U/L and(1083.2±97.2)pg/L,P<0.05]in PL-treated rats;the results of immunohistochemistry showed that the expression of CD163 and iNOS protein in the liver tissues in CL-treated rats were weaker than those in PL-treated rats.Conclusion Hepatic macrophages is involved in the pathogenesis and development of portal hypertension,and needs further investigation.

关 键 词：肝损伤 门脉高压 巨噬细胞 氯膦酸二钠脂质体 大鼠 

分 类 号：R965[医药卫生—药理学]