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一种中药,膈下逐瘀汤(GZT),通过抑制肝星状细胞增殖来预防二甲基亚硝胺诱导的肝纤维化。

A Chinese herbal medicine, Gexia-Zhuyu Tang (GZT), prevents dimethylnitrosamine-induced liver fibrosis through inhibition of hepatic stellate cells proliferation.

机构信息

Department of Life Sciences, and Agricultural Biotechnology Center, National Chung Hsing University, Taichung 402, Taiwan.

出版信息

J Ethnopharmacol. 2012 Aug 1;142(3):811-8. doi: 10.1016/j.jep.2012.06.005. Epub 2012 Jun 15.

Abstract

ETHNOPHARMACOLOGICAL EVIDENCE

Gexia-Zhuyu Tang (GZT), also called Gexiazhuyu decoction (GXZYD), is a traditional Chinese herbal medicine for chronic liver diseases such as cirrhosis and liver fibrosis.

AIM OF THE STUDY

In this study, we have investigated the affects of GZT on a rat model of dimethylnitrosamine (DMN)-induced liver fibrosis.

MATERIALS AND METHODS

In this study, the protective effects of GZT on DMN-induced liver fibrosis were measured using a rat model. Following 5 weeks of DMN-treatment (8 mg/kg, i.p., given 3 consecutive days each week), oral administration of GZT at 1.8 g/kg daily via oral gavage for 2weeks beginning at week 13.

RESULTS

Both body and liver weights were significantly decreased. The reductions in body and liver weights corresponded with increasing liver damage severity. Furthermore, GZT-treatment remarkably decreased the levels of serum GOT (glutamate oxaloacetate transaminase) and GPT (glutamic pyruvic transaminase), and the mRNA expression levels of collagen alpha-1(I) and alpha-smooth muscle actin (alpha-SMA) in DMN-induced hepatic fibrosis. In addition, hepatic stellate cells (HSCs) play a major role in various types of liver fibrosis through initial myofibroblast transformation. The proliferation of HSCs was inhibited by GZT. Treatment with GZT also induced HSC apoptosis in a dose- and time-dependent manner. GZT treatment induced HSC apoptosis by facilitating Ca(2+) release from the mitochondria within 6h. Subsequently, caspases 3 and 12 were elevated by 72 h after treatment.

CONCLUSIONS

Our studies indicate that GZT exhibited both hepatoprotective and antifibrogenic effects in DMN-induced hepatic injury. These findings suggest that GZT may be useful in preventing the development of hepatic fibrosis.

摘要

民族药理学证据

膈下逐瘀汤(GZT),又称膈下逐瘀汤(GXZYD),是一种治疗肝硬化和肝纤维化等慢性肝病的中药。

目的

本研究探讨膈下逐瘀汤(GZT)对二甲基亚硝胺(DMN)诱导的肝纤维化大鼠模型的影响。

材料和方法

本研究采用大鼠模型,观察 GZT 对 DMN 诱导的肝纤维化的保护作用。连续 5 周给予大鼠 8mg/kg 的 DMN(腹腔注射,每周 3 次),第 13 周开始每日通过口服灌胃给予 1.8g/kg 的 GZT 治疗 2 周。

结果

大鼠的体重和肝重均显著下降。体重和肝重的减轻与肝损伤的严重程度呈正相关。此外,GZT 治疗可显著降低血清 GOT(谷氨酸草酰乙酸转氨酶)和 GPT(谷氨酸丙酮酸转氨酶)水平,以及 DMN 诱导肝纤维化大鼠肝组织中胶原 alpha-1(I)和 alpha-平滑肌肌动蛋白(alpha-SMA)的 mRNA 表达水平。此外,肝星状细胞(HSCs)通过最初的肌成纤维细胞转化在各种类型的肝纤维化中起主要作用。GZT 抑制 HSCs 的增殖。GZT 以剂量和时间依赖性方式诱导 HSC 凋亡。GZT 处理可在 6 小时内促进线粒体 Ca(2+)释放,从而诱导 HSC 凋亡。随后,处理后 72 小时 caspase 3 和 12 升高。

结论

本研究表明,GZT 对 DMN 诱导的肝损伤具有保肝和抗纤维化作用。这些发现表明 GZT 可能有助于预防肝纤维化的发展。

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