氯沙坦对90%门静脉结扎大鼠血清肝细胞生长因子水平及肝再生的影响

Effects of losartan on serum HGF and liver regeneration in rats after 90% portal vein ligation

目的探讨氯沙坦对90%门静脉分支结扎（portal branch ligation,PBL）大鼠血清肝细胞生长因子（hepatocyte growth factor,HGF）水平及肝再生的影响。方法 96只雄性Sprague-Dawley（SD）大鼠采用随机数字法分成2组：A组：单纯PBL组（对照组,n=48）,B组：PBL＋2 mg/（kg.d）氯沙坦干预组（治疗组,n=48）,分别于术后0、6、12、24、48、72、120、168 h取大鼠肝脏称质量并计算未结扎侧肝质量占总肝质量比例,心脏取血测ALT及AST,酶联免疫吸附实验（ELISA）检测血清HGF水平,免疫组化方法检测未结扎侧肝组织增殖细胞核抗原（PCNA）的表达。结果①治疗组未结扎侧肝质量与总肝质量比值在24~168 h明显高于对照组（P〈0.01）。②PBL术后2组ALT值迅速升高,12 h达到高峰后逐渐降低。治疗组ALT值在12~48 h明显低于对照组（P〈0.01）;同时PBL术后两组ALT值后迅速升高,12 h达到高峰后逐渐降低。治疗组ALT值在12~72 h明显低于对照组（P〈0.01）。③术后2组血清大鼠HGF浓度迅速升高,并在6 h达到高峰。治疗组在6~168 h明显高于对照组,且下降缓慢（P〈0.01）。④治疗组未结扎侧肝组织PCNA阳性细胞标记率在12~72 h明显高于对照组（P〈0.01）。结论在大鼠90%PBL模型中,氯沙坦可通过介导HGF释放及改善肝功能,促进大鼠的肝再生。

Objective To investigate the effects of losartan on the serum hepatocyte growth factor（HGF） level and liver regeneration after 90% portal branch ligation（PBL） in rats.Methods Ninety-six SD rats were randomly divided into PBL group and treatment group（n=48）.Losartan at 2 mg/（kg·d） was given to the rats of treatment group intragastrically in 2 h after PBL till death.Liver function was evaluated through ALT and AST levels at 0,6,12,24,48,72,120 and 168 h after operation.The weight of both ligated and unligated lobes of liver were measured and the ratio of wet weight of unligated lobes over the whole liver were calculated at the above-mentioned time points.The expression of PCNA in the non-ligated liver lobe was studied with immunohistochemistry.The plasma HGF levels at above time points were measured by ELISA.Results Compared with the PBL group,the ratio of wet weight of unligated lobes over the whole liver was increased in treatment group at 24,48,72,120 and 168 h after operation（P0.01）.ALT level was elevated within the 2 groups after operation,reached its peak value at 12 h after PBL and then decreased gradually,with that of treatment group significantly lower than that in PBL group from 12 to 48 h after PBL（P0.01）.While AST level was elevated immediately after operation,reached its summit at 12 h and then decreased gradually,with that of treatment group significantly lower than that in PBL group from 12 to 72 h after PBL（P0.01）.The postoperative plasma HGF level was increased rapidly and peaked at 6 h after operation.That of the treatment group was significantly higher than that of PBL group at 6,12,24,48,72,120 and 168 h after operation（P0.01）,and slowly declined.The expression of PCNA in the non-ligated liver lobes of the treatment group were significantly higher than that of PBL group at 12,24,48 and 72 h after operation（P0.01）.Conclusion Losartan promotes liver regeneration of unligated lobes of liver after 90% PBL in rats by mediating the release of plasma HGF and improving liver function.