凯西莱联合青霉胺治疗肝豆状核变性模型鼠的研究

Study of Tiopronin combine Penicillamine to treated in rat model with hepatolenticular degeneration

目的探讨凯西莱(MPO)联合青霉胺(PCA)对肝豆状核变性(HLD)模型鼠铜代谢及肝功能的影响。方法采用铜负荷饮食法喂养大鼠制作HLD模型,并分为HLD对照组、MPO组、PCA组及MPO+PCA组,予以相应的药物干预。观察各组大鼠肝铜、24h尿铜及谷氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总蛋白(TP)、白蛋白(ALB)水平变化情况。结果HLD对照组、各药物干预组肝铜、24h尿铜水平较正常对照组显著增高(均P<0.01);MPO+PCA组、PCA组肝铜水平较HLD对照组、MPO组显著降低(均P<0.01),24h尿铜各药物干预组较HLD对照组显著增高(P<0.05～0.01)。ALB水平各药物干预组较HLD对照组显著增高(P<0.05～0.01),各药物干预组间差异无统计学意义。MPO+PCA组ALT、AST水平较HLD对照组、PCA组、MPO组显著降低(均P<0.05),与正常对照组相比差异无统计学意义。结论MPO联合PCA能显著降低HLD模型鼠肝铜水平,促进尿铜排泄,升高血清ALB水平,保护肝功能,效果优于PCA或MPO单用。

Objective To study the effects of Tiopronin （MPO） combine Penicillamine （PCA） on the copper metabolism and function of liver in rats model with hepatolenticular degeneration. Methods To copy hepatolenticular degeneration model rats with copper overloaded diet. Divide the models into groups HLD control, MPO, PCA and MPO ＋ PCA, and interfere with the propotional drugs. To investigate the concentration changes of the lalanine aminotransferase （ ALT）, spartate amino transferase （ AST）, total protein （ TP）, albumin （ ALB ）, liver copper and 24 h urine copper in each group. Results The concentrations of liver copper and 24 h urine copper in HLD control group and each group with drugs intervention were significantly higher than those in normal control group （all P 〈 0. 01 ） ,the concentrations of liver copper in groups MPO ＋ PCA and PCA were significantly lower than those in groups HLD control and MPO （ all P 〈 0.01 ）, the concentrations of the 24 h urine copper in each group with drugs intervention were significantly higher than that in HLD control group（ P 〈 0. 05 ～ 0. 01 ）. The concentrations of ALB in each group with drug intervention were significantly higher than that in HLD control group （ P 〈 0. 05 N 0. 01 ）, but no significant change among them. The concentrations of ALT.AST in MPO ＋ PCA group were significantly lower than those in groups HLD control , PCA and MPO （ all P 〈 0.05 ）, and no significantly diffenrent compared with normal control group. Conclusions The effects of MPO combine PCA can reduce the concentrations of liver copper in HLD rats, and promote the excretion of the 24 h urine copper,increases serum ALB level, protect the function of liver, it is better than use the MPO or PCA individually.