Investigate The Prevention Of Angelica Sinensis Polysaccharide On The Rats From Hepatic Encephalopathy And Its Mechanism

Objective:There are more and more hepatopathes in our country, many of them suffered from hepatic cirrhosis in the end, complicting with hepatic encephalopathy(HE). Survival rate of the HE patients is low, prognosis is pessimistic, which influence ones'lifetime and living quality. But, at present, there have not been one specific medicine at present which could cure hepatic cirrhosis and HE, people continued investing the pathophysiology and remedy of HE. Existing widespread point is hyperammoniemia would play an important role in the development of HE. Ammonia permeate through blood brain barrier, diffuse in brain. then under the catalysis of glutamine synthetase(GS), energized with adenosine triphosphate, ammonia and glutamate synthesis glutamine in astrocyte. Astrocytes are the only ones in brain have GS, representative of the main position detoxify amonia in brain, also the the main position to uptake excitatory amino acids glutamate. When the concentration of ammonia increased, astrocytes swelling and nutritional support to neurons decreased, uptake of excitatory amino acids glutamate decreased, glutamate keep on stimulating neurons. Astrocytes'synthesis capability of glutamine from ammonia and glutamate weaken, therefore the concentration of brain ammonia increase, forming infernal circle. How to break the circle may be a new way to HE remedy and semiotic improvement. Angelica Sinensis Polysaccharide(ASP) is the main water-soluble composition of our traditional Chinese medicine angelica, have multi-efficacy. Angelica Sinensis Polysaccharide is extracted from angelica root, not only gross Polysaccharide but also its ingredients, all have therapeutical effect to hepatic damage. ASP can interfered in acute alcohol hepatic injury of mouse, increased liver energy reserve and against lipid peroxidation. ASP can also protect well mouse from carbon tetrachloride hepatic injury, increase serum aspartate aminotransferase and liver glutathione s-transferase activey. So, we suppose that ASP could have therapeutical effect to hepatic cirrhosis and HE induced by chronicity carbon tetrachloride poisoning.The objective of this experiment is to investigate whether ASP extracted from angelica root have effect to hepatic cirrhosis rats induced by carbon tetrachloride, and whether it can delay HE onset, and discuss its possible mechanism, thus find out a new therapeutics of hepatic cirrhosis and HE.Methods:Part one: ASP was isolated by ethanol precipitation after water extraction with microwave assisting, then determined the gross polysaccharides consents with Phenol-sulfuric method.Part two: S-Dawley rats were divided into normal control and induction group randomly. Induction group hypodemic injected with 40% carbon tetrachloride solution, 63 days later, coma was induced using endotoxin 3mg/kg peritoneal injection. Observe each group rats'liver pathology and electroencephalogram(EEG) characters.Part three: S-Dawley rats were also divided into normal control,negative,positive medicine,ASP10g/L,ASP20g/L,ASP40g/L six groups randomly. Besides normal control, others were hepatic cirrhosis rats. Each group was intragastric administrated respectively with distilled water,distilled water,lactulose,ASP10g/L,ASP20g/L,ASP40g/L solution. 2 weeks later, endotoxin peritoneal injected. Record coma occur time, determine serum ammonia,glutamate-pyruvate transaminase(GPT), glutamic oxaloacetic transaminase (GOT),and brain apoptosis amount,astrocyte amount, brain tissue protein contents of glutamate transporter(GLT) and GS.Results:Part one: ASP was extracted from angelica root, its gross polysaccharides content was 68%.Part two: induction rats'liver shaped pseudolobule, hepatic cirrhosis induction successed. Induction group rats'serum ammonia obviously higher than before induced(P<0.01)。after endotoxin injection, induced rats occurred coma, EEG appear characteristic curve. Normal control rats'serum ammonia have no significant difference compared with before experiment, no coma occur after endotoxin injection, EEG curve was normal.Part three: positive medicine Lactulose and ASP every dose groups could delay hepatic cirrhosis rats'HE occur, decreased their serum ammonia,GPT,GOT,reduced brain apoptosis,increased astrocytes,raised brain tissue protein GLT and GS。ASP40g/L solution could postpone more time to HE,get lower serum amonia,GOT,less brain apoptosis,more astrocytes and GLT contents compared with Lactulose(P<0.05). Conclusions:ASP have effects to hepatic cirrhosis induced by carbon tetrachloride, can delay HE occur. Its mechanism probably involve in improving hepatic function, decrease serum ammonia,GPT,GOT; protect brain cells, reduce apoptosis; increase astrocyte, brain tissue protein GLT and GS, enhance brain ammonia deintoxication ability.