Shin Jang-Woo, Son Jin-Young, Oh Se-Mi, Han Seung-Hyun, Wang Jing-Hua, Cho Jung-Hyo, Cho Chong-Kwan, Yoo Hwa-Seung, Lee Yeon-Weol, Lee Myong-Min, Hu Xiao-Ping, Son Chang-Gue
East-West Cancer Center, Dunsan Oriental Hospital of Oriental medical College of Daejeon University, 1136 Dunsan-dong, Seo-gu, Daejeon 302-122, South Korea.
World J Gastroenterol. 2006 Oct 14;12(38):6142-8. doi: 10.3748/wjg.v12.i38.6142.
To evaluate the therapeutic effect of Chunggan extract (CGX), a modified traditional Chinese hepatotherapeutic herbal, on the dimethylnitrosamine (DMN)-induced chronic liver injury model in rats.
Liver injuries were induced in Wistar rats by injection of DMN (ip, 10 mg/mL per kg) for 3 consecutive days per week for 4 wk. The rats were administered with CGX (po, 100 or 200 mg/kg per day) or distilled water as a control daily for 4 wk starting from the 15(th) d of the DMN treatment. Biochemical parameters (serum albumin, bilirubin, ALP, AST and ALT), lipid peroxides, hydroxyproline, as well as histological changes in liver tissues were analyzed. In addition, gene expression of TNF-alpha, TGF-beta, TIMP-1, TIMP-2, PDGF-beta, and MMP-2, all of which are known to be associated with liver fibrosis, were analyzed using real-time PCR.
CGX administration restored the spleen weight to normal after having been increased by DMN treatment. Biochemical analysis of the serum demonstrated that CGX significantly decreased the serum level of ALP (P < 0.05), ALT (P < 0.01), and AST (P < 0.01) that had been elevated by DMN treatment. CGX administration moderately lowered lipid peroxide production and markedly lowered hydroxyproline generation caused by DMN treatment in accordance with histopathological examination. DMN treatment induced a highly up-regulated expression of TNF-alpha, TGF-beta, TIMP-1, TIMP-2, PDGF-beta, and MMP-2. Of these, the gene expression encoding PDGF-beta and MMP-2 was still further enhanced 2 wk after secession of the 4-wk DMN treatment, and was remarkably ameliorated by CGX administration.
CGX exhibits hepatotherapeutic proper-ties against chronic hepatocellular destruction and consequential liver fibrosis.
评估改良传统中药肝治疗草药——清肝提取物（CGX）对二甲基亚硝胺（DMN）诱导的大鼠慢性肝损伤模型的治疗效果。
通过每周连续3天腹腔注射DMN（10 mg/mL每千克），持续4周，诱导Wistar大鼠肝损伤。从DMN治疗的第15天开始，大鼠每天口服CGX（100或200 mg/kg）或蒸馏水作为对照，持续4周。分析生化参数（血清白蛋白、胆红素、碱性磷酸酶、天冬氨酸转氨酶和丙氨酸转氨酶）、脂质过氧化物、羟脯氨酸以及肝组织的组织学变化。此外，使用实时聚合酶链反应分析已知与肝纤维化相关的肿瘤坏死因子-α、转化生长因子-β、金属蛋白酶组织抑制因子-1、金属蛋白酶组织抑制因子-2、血小板衍生生长因子-β和基质金属蛋白酶-2的基因表达。
CGX给药使DMN治疗后增加的脾脏重量恢复正常。血清生化分析表明，CGX显著降低了DMN治疗后升高的血清碱性磷酸酶水平（P < 0.05）、丙氨酸转氨酶水平（P < 0.01）和天冬氨酸转氨酶水平（P < 0.01）。根据组织病理学检查，CGX给药适度降低了脂质过氧化物的产生，并显著降低了DMN治疗引起的羟脯氨酸生成。DMN治疗诱导肿瘤坏死因子-α、转化生长因子-β、金属蛋白酶组织抑制因子-1、金属蛋白酶组织抑制因子-2、血小板衍生生长因子-β和基质金属蛋白酶-2的高度上调表达。其中，在4周DMN治疗停止后2周，编码血小板衍生生长因子-β和基质金属蛋白酶-2的基因表达仍进一步增强，而CGX给药可显著改善这种情况。
CGX对慢性肝细胞破坏及随之而来的肝纤维化具有肝治疗特性。
