龍膽瀉肝湯變方對Dimethylnitrosamine誘發大鼠肝損傷的療效探討

STUDIES ON THE THERAPEUTIC EFFECTS OF DEVIATED LONG-DAN-XIA-GAN-TANG ON DIMETHYLNITROSAMINE INDUCED HEPATIC DAMAGE IN RATS

本研究擬以大白鼠接受Dimethylnitrosamine （DMN ）方式引致肝損傷，同時以《蘭室秘藏》中之龍膽瀉肝湯加減方分別給予高劑量（333 mg/kg ）及低劑量（111 mg/kg ），以胃管餵食每天一次連續四週方式，以評估其對保肝和抗纖維化療效。評估方法和測量指標包括：（1 ）血清生化如GOT 、GPT 和血清總蛋白量及白蛋白量測定，（2 ）肉眼病變觀察，（3 ）組織病理中肝細胞變性、壞死及纖維化之判讀評分比較，（4 ）肝組織中膠原蛋白含量定量分析。結果如下：DMN 引致肝損傷大鼠中，餵食龍膽瀉肝湯變方低劑量及高劑量組之GOT （213.2 ± 16.3 U/l 、193.0 ± 9.6 U/l ）均比DMN 組（394.8 ± 28.2 U/l ）顯著性降低（p < 0.01 ），低劑量及高劑量組之GPT （149.1 ± 5.9 U/l 、93.8 ± 7.8 U/l ）與DMN 組（253.1 ± 6.4 U/l ）亦顯著性降低（p < 0.05 ）。但血清總蛋白量及白蛋白量，只龍膽瀉肝湯變方高劑量組（6.2 ± 0.2 & 4.4 ± 0.1 g/dL ）與DMN 組（5.8 ± 0.4 & 4.1 ± 0.2 g/dL ）比較則有顯著性差異（p < 0.05 ）的情形。在肉眼病變發現DMN 組之肝、腎明顯變黃和萎縮，與高劑量餵食龍膽瀉肝湯變方組之肝、腎重比較有顯著性差異（p< 0.05 ）。以組織病理之觀察並評分，在肝細胞的變性、壞死程度情形龍膽瀉肝湯變方組均較DMN 組輕微（p < 0.05 ），但肝纖維化程度差異較不明顯（p > 0.05 ）。肝組織中膠原蛋白含量比較，龍膽瀉肝湯變方組之肝組織膠原蛋白含量稍低於DMN 組但無顯著性差異（p > 0.05 ）。由此研究得一結論，龍膽瀉肝湯變方組對保護肝臟損傷及降低肝細胞的變性和壞死程度有明顯功效，但對抗纖維化效果則不明顯，依據中醫的基礎理論－－ 辨證論治，本方劑比較適合用於初期屬於急性濕熱較重的發炎期證型，而對於進入慢性肝炎肝纖維化時比較不適合。To assay the hepatic protection and the anti-cirrhotic effect of Long-Dan-Xia-Gan-Tang, we used dimethylnitrosamine (DMN) to induce liver damage in rats. These rats were first fed with 1 % DMN three times per week for 4 weeks, and were then fed with low and high doses (111 mg/kg, 333 mg/kg) of this herbal drug once time per day for 4 weeks. Assay indicators for the therapeutic effect include: 1) serum biochemical tests, such as GOT, GPT, total protein and albumin, 2) gross lesion findings, 3) histopathological score of degeneration, necrosis of hepatocyte, and hepatic fibrosis, and 4) collagen determination in liver tissues. The results show that this herbal drug significantly decreased the contents of GOT (p < 0.05), GPT (p < 0.05), total protein and albumin (p < 0.05), and the degrees of DMN-induced hepatic degeneration and necrosis (p < 0.05). However, the occurrence of hepatic fibrosis in histopathological score and the collagen determination were not significantly different from those in the control rats (p > 0.05). These findings indicate that Lon-Dan-Xan-Tang exerted significant effects on the hepatic protection, but not on the inhibition of hepatic fibrosis. Conclusively, this herbal drug may have therapeutical role in the acute stage of liver disease.