To investigate the effects and to elucidate the mechanism of Chinese herbs Recipe(consisting of Rhizoma Atractylodis Macrocephalae, Radix Salviae Simplicifoliae, Fructus Aurantii, et al) on antagonizing alcoholic live...To investigate the effects and to elucidate the mechanism of Chinese herbs Recipe(consisting of Rhizoma Atractylodis Macrocephalae, Radix Salviae Simplicifoliae, Fructus Aurantii, et al) on antagonizing alcoholic liver injury from the pathological relationship between alcoholic liver injury, gut permeability and endotoxin leakage. The SD rats were fed the Lieber- Decarli liquid alcohol die(t35% of calories from alcohol)to deveclp the alcoholic liver injury model. 42 male SD rats were divided into 4 groups:normal group(n=6),no- alcohol liquid diet group in which alcohol was replaced with carbohydrates(Control group, n=12), alcohol liquid diet group(alcohol group, n=12) and alcohol liquid eiet with Chinese herbs group(herbs group, n=12). Starting from the third week, the rats were fed distilled water, no- alcohol liquid diet, alcohol liquid diet or alcoholic liquid diet with Chinese herbs by intragastric infusion for 6 weeks. Then the rats were fast for 5 h. After that, each group received 10 mg/kg of endotoxin(lipidopolysacchride, LPS)by intragastric infusion. 3.5 hours later, the blood from portal vein and vena cava was harvested and liver biopsy was performed to analyze:1. The histopathological change in small intestine (HE staining and electron microscopic observation); 2. The histopathological change in liver(HE staining, oil red O staining); 3. The TG and r- GT activities in liver and the ALT, AST activities in serum; 4. The plasma endotoxin level in portal vein blood; 5. The protein expressions(on Wetern blot) of P- I k B and TNF- a in liver.Results: that It is 1.Fatty degeneration was seen in over 1/3 of the heptocytes in the alcohol group. The liver TG level in this group was about 7.3 times higher than that in the normal group and 4.9 times higher than that in the control group. In addition, the serum ALT, AST activities as well as liver r- GT activity in the alcohol group were significantly elevated than those in the normal and control group. Observation under electron microscopy revaled swelling, degeneration, shortening and irregular array of microvilli on the surface of the small intestinal epithelial cells. 2. Compared to that from the severe. In the herbs group, the liver TG level was 67% of that in the alcolol group and the serum ALT level was close to normal level. Moreover, the ultramicrostructural lesions in small intestine was obviously alleviated. 3. The plasma endotoxin level in portal vein reached as high as 3.93+- 0.32 EU/ml in the alcohol group, which was 2.1 times that of normal group and 1.6 times of the control group, indicating that the gut permeability was remarkably increased in the alcohol group. In contrast, the endotoxin level in the herbs group was 85% of the alcohol group(P<0.05). 3. In the alcohol group, the protein expression of P- I k B and TNF- a in the liver and TNF- a level in the plasma were greatly increased compared to those in the normal and control groups. But those changes were much improved in the herbs group. Correlation analysis showed that the TNF- a level was clearly positively correlated with the plasma endotoxin level (r=0.85,p<0.001). The ALT activity and TNF- a level were obviously positively correlated too (r=0.78,P<0.001). It is Conclused that 1. Alcohol could increase the rat gut permeability. The leakage of endotoxin through small intestine played a major role in the pathogenesis of alcohol liver diseases. 2. The Recipe had the effects of protecting the rat liver and intestine from alcohol damage. 3. It’s one of the important mechanisms for the Recipe to antagonize the alcoholic liver injury by lovering the increased gut permeability by alcohol, decreasing the absorption of endotoxin through small intestine, which in turns inhibited the activation of NF- k B and the synthesis of TNF- a, a major inflammatory cytokine. 4. It’s worth further in vestigation to“treat from Spleen”of alcoholic liver diseases. Improving the intestinal function could be the key to treatment and prevention of the alcoholic liver diseases.展开更多
文摘To investigate the effects and to elucidate the mechanism of Chinese herbs Recipe(consisting of Rhizoma Atractylodis Macrocephalae, Radix Salviae Simplicifoliae, Fructus Aurantii, et al) on antagonizing alcoholic liver injury from the pathological relationship between alcoholic liver injury, gut permeability and endotoxin leakage. The SD rats were fed the Lieber- Decarli liquid alcohol die(t35% of calories from alcohol)to deveclp the alcoholic liver injury model. 42 male SD rats were divided into 4 groups:normal group(n=6),no- alcohol liquid diet group in which alcohol was replaced with carbohydrates(Control group, n=12), alcohol liquid diet group(alcohol group, n=12) and alcohol liquid eiet with Chinese herbs group(herbs group, n=12). Starting from the third week, the rats were fed distilled water, no- alcohol liquid diet, alcohol liquid diet or alcoholic liquid diet with Chinese herbs by intragastric infusion for 6 weeks. Then the rats were fast for 5 h. After that, each group received 10 mg/kg of endotoxin(lipidopolysacchride, LPS)by intragastric infusion. 3.5 hours later, the blood from portal vein and vena cava was harvested and liver biopsy was performed to analyze:1. The histopathological change in small intestine (HE staining and electron microscopic observation); 2. The histopathological change in liver(HE staining, oil red O staining); 3. The TG and r- GT activities in liver and the ALT, AST activities in serum; 4. The plasma endotoxin level in portal vein blood; 5. The protein expressions(on Wetern blot) of P- I k B and TNF- a in liver.Results: that It is 1.Fatty degeneration was seen in over 1/3 of the heptocytes in the alcohol group. The liver TG level in this group was about 7.3 times higher than that in the normal group and 4.9 times higher than that in the control group. In addition, the serum ALT, AST activities as well as liver r- GT activity in the alcohol group were significantly elevated than those in the normal and control group. Observation under electron microscopy revaled swelling, degeneration, shortening and irregular array of microvilli on the surface of the small intestinal epithelial cells. 2. Compared to that from the severe. In the herbs group, the liver TG level was 67% of that in the alcolol group and the serum ALT level was close to normal level. Moreover, the ultramicrostructural lesions in small intestine was obviously alleviated. 3. The plasma endotoxin level in portal vein reached as high as 3.93+- 0.32 EU/ml in the alcohol group, which was 2.1 times that of normal group and 1.6 times of the control group, indicating that the gut permeability was remarkably increased in the alcohol group. In contrast, the endotoxin level in the herbs group was 85% of the alcohol group(P<0.05). 3. In the alcohol group, the protein expression of P- I k B and TNF- a in the liver and TNF- a level in the plasma were greatly increased compared to those in the normal and control groups. But those changes were much improved in the herbs group. Correlation analysis showed that the TNF- a level was clearly positively correlated with the plasma endotoxin level (r=0.85,p<0.001). The ALT activity and TNF- a level were obviously positively correlated too (r=0.78,P<0.001). It is Conclused that 1. Alcohol could increase the rat gut permeability. The leakage of endotoxin through small intestine played a major role in the pathogenesis of alcohol liver diseases. 2. The Recipe had the effects of protecting the rat liver and intestine from alcohol damage. 3. It’s one of the important mechanisms for the Recipe to antagonize the alcoholic liver injury by lovering the increased gut permeability by alcohol, decreasing the absorption of endotoxin through small intestine, which in turns inhibited the activation of NF- k B and the synthesis of TNF- a, a major inflammatory cytokine. 4. It’s worth further in vestigation to“treat from Spleen”of alcoholic liver diseases. Improving the intestinal function could be the key to treatment and prevention of the alcoholic liver diseases.
