马洛替酯抑制肝纤维化的实验与临床研究

Inhibitory effect of malotilate on hepatic fibrosis in mice and chronic hepatitis patients

目的研究国产马洛替酯抑制小鼠肝纤维化的作用．方法对Ｂａｌｂ／ｃ小白鼠用４００ｍＬ／ＬＣＣｌ４橄榄油溶液２ｍＬ／ｋｇ，ｉｇ，１次／ｗｋ，同时自由饮用５０ｍＬ／Ｌ酒精水溶液，治疗组于ｗｋ１６起加马洛替酯５０或１００ｍｇ／（ｋｇ·ｄ），ｉｇ，５ｄ／ｗｋ．ｗｋ２４末断头处死，取血检查谷丙转氨酶（ＡＬＴ）、清蛋白（Ａｌｂ）剖腹取肝，部分作病理检查，ＨＥ和ＶＧ染色，观察肝纤维化分期；部分制成１００ｇ／Ｌ肝匀浆测定肝组织中羟脯氨酸（Ｈｙｐ）、透明质酸（ＨＡ）含量．选择４０例中度慢性乙型病毒性肝炎，随机分２组，采用双盲法给药，治疗前及３ｍｏ后，检测血清ＡＬＴ，Ａｌｂ，Ⅲ型前胶原肽（ＰⅢＰ）及透明质酸（ＨＡ）．结果模型组绝大多数小鼠肝脏形成了假小叶，肝组织Ｈｙｐ（ｍｇ／ｇ），ＨＡ含量（ｍｇ／ｇ）是３７０±２１２，２１３±０３４．治疗组Ⅳ，Ⅴ组Ｈｙｐ含量是２２３±６０，１６１±１０；ＨＡ含量是１３４±０１４，０５３±０１７．治疗组Ａｙｐ，ＨＡ含量较模型组明显减少（Ｐ＜００５）．慢性肝炎患者治疗３ｍｏ后，血清ＰⅢＰ（ｋＵ／Ｌ），ＨＡ含量（ｍｇ／Ｌ）分别是１４±１０，７４５±２７６；安慰剂组ＰⅢＰ?

AIM The inhibitory effect of malotilate on hepatic fibrosis was studied in mice and chronic hepatitis patients. METHODS Balb/c mice were given orally 400mL/L CCl 4 with olive oil 2mL/kg , once a week with free access to 50mL/L alcohol for 24 weeks. In the treated group (Ⅳ,Ⅴ), administration of malotilate (50, 100mg/kg) 5 times a week started 16 weeks after the beginning of experiment and continued until week 24. Forty patients with chronic hepatitis (moderate degree) were randomly divided into two groups, treated group and placebo group. The patients were followed up for 3 months. RESULTS The liver in most of mice in pathologic model group formed pseudolobule. Hepatic hydroxyproline (Hyp, mg/g) and hyaluronic acid (HA, mg/g) contents were 37 0±21 2, 2 13±0 34 respectively. In the treated group (Ⅳ and Ⅴ), the contents of hepatic Hyp (mg/g) were 22 3±6 0, 16 1±1 0; HA (mg/g) were 1 34±0 14, 0 53±0 17, respectively. The contents of hepatic Hyp and HA were significantly reduced in the treated group than that in pathologic model group ( P <0 05). After treatment for 3mo , the serum levels of procollagen Ⅲ peptide (PⅢP, kU/L) and HA (mg/L) in treated group of chronic hepatitis were 1 4±1 0,74 5±27 6; in the placebo group, PⅢP and HA were 2 2±1 6, 137 4±46 5, respectively. The serum levels of PⅢP and HA in treated group was significantly lower compared to placebo group( P <0 05). CONCLUSION The hepatic fibrosis in mice and chronic hepatitis patients can be inhibited by malotilate.