目的探讨复方肝毒清对二甲基亚硝胺（DMN）诱导肝纤维化大鼠肝组织转化生长因子-β1（TGF-β1）、诱导型一氧化氮合酶（iNOS）、肿瘤坏死因子a（TNF—a）的mRNA表达的影响。方法采用每周连续3d腹腔注射DMN10／ul／kg共4周制备大鼠肝纤维化模型（70只），并设对照组（10只）。第2周开始，将70只模型大鼠按随机数字表法分为模型组、秋水仙碱组、氯化钆（GdCl3）组以及复方肝毒清高、低剂量组，后4组分别灌胃秋水仙碱0．01mg／kg、腹腔注射GdCl3 40mg／kg及灌胃中药复方肝毒清20g／kg、5g／kg；对照组及模型组均灌胃生理盐水10ml／kg；均每日1次，连用21d。采用定量聚合酶链反应（PCR）检测肝组织TGF—β1、iNOS、TNF-a的FiRRNA表达。结果中药复方肝毒清不仅能减轻肝组织铁的沉积，抑制胶原纤维的增生，减少假小叶的形成；而且能不同程度下调TGF—β1、iNOS、TNF—a的mRNA表达，以高剂量组较显著，与模型组比较差异有统计学意义（TGF—β1mRNA：6．32±1．19比16．15±2．39，iNOSmRNA：18．73±2．13比43．15±6．39，TNF-amRNA：3．69±1．22比8．68±2．13，均P〈0．01）。结论铁沉积于库普弗细胞在肝纤维化发生发展过程中发挥重要作用，复方肝毒清的抗肝纤维化机制可能与其调节体内铁的代谢有关。[著者文摘]
Abstract:
Objective To investigate the effects of compound Ganduqing decoction （复方肝毒清） on mRNA expressions of transforming growth factor-β1 （TGF-β1）, inducible nitric oxide synthase （iNOS）, tumor necrosis factor-a （TNF-a） in rats of N-Nitrosodimethylamine （DMN） induced liver fibrosis. Methods Rat liver fibrosis models were established by DMN intraperitoneal injection at a dose of 10 ul/kg daily, for 3 consecutive days each week for 4 weeks, and blank controlgroup （10 rats） was made. Fromthe second week, 70 rats for liver fibrosis models were randomly divided into model group, colchicine group, GdCl3 group, compound Ganduqing high-dose and low-dose groups. Rats of the last four groups were treated by gastric infusion at the dosage of colchicine 0.01 mg/kg, intraperitoneal injection of GdCl3 40 mg/kg, gastric perfusion of compound Ganduqing decoction at the dosage of 20 g/kg and 5 g/kg, respectively. The model group and blank control group were both infused gastrically with normal saline at 10 ml/kg. All groups were treated once daily for 21 days. Quantitative polymerase chain reaction （PCR） was applied to detect expressions of TGF-β1, iNOS and TNF-a mRNA. Results Compound Ganduqing not only could reduce iron deposition, prevent the proliferation of collagen fibers and decrease pseudolobule formation in liver, but also could down-regulate TGF-β1, iNOS and TNF-a mRNA expressions of liver tissue, which were more considerable in the Ganduqing high-dose group. Compared with the model group, there were statistical significant differences （TGF-β1 mRNA： 6.32±1. 19 vs. 16.15±2.39, iNOS mRNA： 18.73±2.13 vs. 43.15±6.39, TNF-a mRNA： 3.69± 1.22 vs. 8.68±2.13, all P〈0.01）. Conclusion Iron deposition in Kupffer cells may play an important role in the genesis and development of liver fibrosis. Compound Ganduqing can ameliorate liver fibrosis, whose anti-fibrosis mechanism might be related to Ganduqing regulatory action on iron metabolism of liver tissues.[著者文摘]
Key words:
Liver fibrosis; Kupffer cell; Iron; Traditional Chinese medicine therapy
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