Clinical And Experimental Study Of Ganoderma Lucidum Dcoction On Acute Amatoxin Mushroom Poisoning

Objective:To assess the treatment effect,pharmacologic action and disintoxication mechanism of Amanita Mushroom Poisoning with Glossy Ganoderma Decoction by the way of systemic clinical investigation and animal experiments based on Traditional Chinese Medicine theory after getting primary clinical therapeutic effect.Methods:1.Clinical Experience in Treatment of Amanita Mushroom Poisoning with Glossy Ganoderma Decoction:According to the degree of poisoning,103 patients with acute Amanita mushroom poisoning (AAMP) were divided into:(1) Slightly poisoning group,32 cases,the Glossy ganoderma decoction was prepared by taking 100g Glossy ganoderma to be decocted with water to 1000ml,and 250ml was given q.i.d,for successive 7 days.(2) Moderately poisoning group,37 cases,the Glossy ganoderma decoction was prepared by taking 200g Glossy ganoderma to be decocted with water to 1500ml,and 250ml was given six times per day for successive 7 days.(3) Severely poisoning group,34 cases,the Glossy ganoderma decoction was prepared by taking 300g Glossy ganoderma to be decocted with water to 2000ml,and 250ml was given eight times per day for successive 7 days.The therapeutic beneficial effects and the alterative levels of serum total bilirubin(STB), direct bilirubin(UBS),bile acids(BA),alanine transaminase(ALT) and aspartate transaminase(AST) activities in both groups were compared.2.Rabbit Model of Amanita Mushroom Poisoning Established: Sixteen healthy rabbits(8 months year old,weight 2kg per rabbit) were randomly divided into:(1) Control group with physiological saline intragastric administration.(2) Experimental groupⅠ,the crude Glossy ganoderma extraction was given with the dose of 0.05g/kg.(3) Experimental groupⅡ,the crude Glossy ganoderma extraction was given with the dose of 0.1g/kg.(4) Experimental groupⅢ,the crude Glossy ganoderma extraction was given with the dose of 0.2g/kg.There were 4 rabbits in each group.The animal poisoning,animal mortality and the alterative levels of serum total bilirubin(STB),direct bilirubin(UBS), bile acids(BA),alanine transaminase(ALT) and activities in all groups were investigated.Blood samples were collected respectively before experiment,at the 3^th and 5^th day after experiment for laboratory studies mentioned above.All animals were killed at the 5^th day after experiment for hepatic pathological examination.3.Experimental Study on Treatment of Amanita Mushroom Poisoning with Glossy Ganoderma Decoction:Two kinds of decoctions were prepared:400g/L crude Glossy ganoderma extraction was made by Amanita Mushroom Poisoning.Two decoctions including 100%Glossy Ganoderma Decoction and 300%Glossy Ganoderma Decoction were made by ganoderma cut crude drug.Twenty healthy New Zealand rabbits were randomly divided into:(1) Control group with physiological saline intragastric administration.(2)Poisoning model group,after being given the crude Glossy ganoderma extraction with the dose of 100mg/kg,this group was given physiological saline.(3) Treatment groupⅠ,after being given the crude Glossy ganoderma extraction with the dose of 100mg/kg,the 100%Glossy ganoderma Decoction was given q.d for successive 5 days.(4) Treatment groupⅡ,after being given the crude Glossy ganoderma extraction with the dose of 100mg/kg,the 300% Glossy ganoderma Decoction was given q.d for successive 5 days.There were 5 rabbits in each group.The indexes of observation and monitoring:①Evaluation of animal mortality.②The laboratory indexes study include serum total bilirubin(STB),direct bilirubin(UBS),bile acids (BA),alanine transaminase(ALT),aspartate transaminase(AST),lactate dehydrogenase(LDH),lactate dehydrogenase isoenzyme(α-HBDH), creatine kinase(CM),creatine kinase isoenzyme(CK-MB),.Blood samples were collected respectively before experiment,at the 3^th and 5^th day after experiment for laboratory studies mentioned above.③Hepatic cell RNA polymerase.④hepatic pathological examination.Results:1.The therapeutic outcome and effects:103 patients with acute Amanita mushroom poisoning were rescued successfully without case mortality.The continuous observation of these blood biochemical parameters showed that the elevation of these blood biochemical parameters were temperate during the treatment.These blood biochemical parameters rapidly decreased during the successive treatment and returned or were close to normal level.2.Rabbit Model of Amanita Mushroom Poisoning Established:①Animal mortality:All rabbits survived after experiment in the control group and experiment groupⅠ.Two rabbits died during experiment in experiment groupⅡ.All rabbits died at the 3^th or 5^th day after the experiment in experiment groupⅢ.②The biochemical parameters of the poisoning model group showed:The liver function indexes were normal during the experiment.The blood biochemical parameters in the experiment groups showed that the degree of the liver function positively related to the dose of poisoning and progressively aggravated,the differences of the liver function among the experiment groups were highly significant(P＜0.01).③Hepatic pathological changes in the poisoning model:The structure of hepatic lobule was normal and no hepatic cell necrosis in the control group.The hepatic cell of the rabbits died in the course of the experiment necrosis foliated and dissolved hepatic sinusoid congestion.The hepatic cell of the rabbits killed after the experiment apomorphosis and necrosis foliated or punctiform.The model was established successfully.If the model was established with the concentration of 400%amanita mushroom poisoning,the suitable dose would be 100mg%.3.Experimental Study on Treatment of Amanita Mushroom Poisoning with Glossy Ganoderma Decoction:①Animal mortality: All rabbits survived after experiment in the control group and the treatment groups.Two rabbits died during experiment in the poisoning model group.②The biochemical parameter of liver function:These indexes were normal in the course of the experiment in the control group but damaged markedly in other groups.These indexes returned to normal rapidly in the treatment groups but were progressively aggravated in the poisoning model group.The differences of the liver function between the groups were highly significant(P＜0.01),so were the changes of the cardiac creatase.③The relationship between Glossy Ganoderma Decoction and the RNA polymerase activity:the Glossy Ganoderma Decoction can activate the RNA polymerase and the doses of the Glossy Ganoderma Decoction were positively related to the RNA polymerase activity.④Amanita Mushroom Poisoning can decrease the RNA polymerase activity markedly.⑤The efficacy on treatment of Amanita Mushroom Poisoning with Glossy Ganoderma Decoction:the Glossy Ganoderma Decoction has strong effect on liver protection which was relative to the dose of the Glossy Ganoderma Decoction.⑥Hepatic pathological changes in the poisoning model:The structure of hepatic lobule was normal and no hepatic cell necrosis in the control group.The hepatic cell of the rabbits died in the course of the experiment necrosis foliated and dissolved hepatic sinusoid congestion.The hepatic cell of the rabbits killed after the experiment apomorphosis and necrosis foliated or punctiform.Conclusions:1.Clinical study showed that Glossy Ganoderma Decoction can obtain perfect effect on the treatment of Amanita Mushroom Poisoning without rabbit mortality.The blood biochemical parameters showed that Glossy Ganoderma Decoction has good effect on organ protection.2.The poisoning model was established successfully using rabbits.If the model was established with the concentration of 400%amanita mushroom poisoning,the suitable dose would be 100mg%.The features of the model:①The acute poisoning symptoms of Amanita Mushroom Poisoning is similar to the clinical symptoms.②The behaviors of the poisoning models were as the same as seen at the clinic.③The quantitative,qualitative,histological hepathologiological function indexes and damage were consistent with the clinic.3.The Glossy Ganoderma Decoction has strong effect on liver protection which positively relate to the dose of the Glossy Ganoderma Decoction.4.One of the detoxicative mechanisms of the treatment of Amanita Mushroom Poisoning with Glossy Ganoderma Decoction is to activate the RNA polymerase of hepatic cell.