| Acetaminophen ( APAP) , also called paracetamol, presently as an effective and cheap antipyretic - analgesic agent, is widely used among the folk. When used in the effective dose, the tolerance of APAP is good, and side effect is less, but APAP toxicosis is still a common poisoning in the clinic. The main manifestations will be medicine hepatitis, acute hepatic necrosis, and hepatic failure, even death. Alcohol is hepatophilic, and liver is the only organ for alcohol metabolism. Long - term drinking result in repeatedly degeneration, necrosis , and regeneration of hepatic cell, finally lead to hepatic fibrosis and cirrhosis; the most common type is fatty liver.At present, there is no report about the relative susceptibility and mechanism of APAPs hepatic toxicities for alcoholic liver disease. For the restriction of studying in the human body, this trial detects hepatic pathologic change, hepatic enzyme, and intracellular factors mainly though normal rat and rat model with alcoholic liver disease using alcohol pour into the stomach, and then discuss the relative susceptibility and mechanism of the APAPs hepatic damage to the alcoholic liver disease.Material and method1. Material and steps(1) Preparation of the rat with alcoholic liver disease: In group C and D both are 10 healthy male Wistar rat, with the body weight 180g ~220g, and are both given 400ml/L alcohol, 8g/kg. d, three times pouring into stomach till theend of 4th week; from 5th week, increase alcohol concentration to 500ml/L, 9g/kg. d, till 8th week.(2) Divided 40 rats into 4 group: Group A is controlled group, group B is Acetaminophen group, group C is alcoholic liver disease group, group D is alcoholic liver disease and Acetaminophen group, each group has 10 rats.(3) Give 450mg/kg Acetaminophen injected into the abdomen to group B group D with 8 weeks feeding of alcohol; and group A C are infected with the same amount of 0.9%NaCl . 8 hours later, use 10% chloral hydrate 4ml/kg as abdominal anesthesia, then lie on its back and fix it, and make median incision in the neck, completely expose right jugular vein, draw out 5ml venous blood from each rat; open the thorax and abdomen, expose the heart, open the pericardium, cut auricular dextra using scissor, rapid inject PBS buffer fluid with the needle punctured into the left ventricle, which though body circulation flow out from auricular dextra; repeat the above process, till the color of liver change from fresh red to pale. Bring out liver tissue of rats, wash them using 10% formalin , fix more than 24 hours, bury them into olefin and resects, after de - ole-fin and make HE stain, observe the correlated cellular change under microscope.2. Detection(1) Using chemical method detect the level of AST ALT MDA GSH SOD in the blood and using radio - immune method detect IL - 6 level.(2) Use microscope to observe hepatic necrosis, the detection of hepatic cell apoptosis, olefin resection routinely hydrolyze, then use DNA terminal local mark stain agent to measure, proceed according to the showing step. At last, generally DAB stain, haematoxylin slightly stain, neutral balata fixation.(5) Judgment hepatic cell apoptosis degree: cell nucleus brown staining is regard as positive; no cell nucleus brown staining is regard as negative. Use apoptosis ( select 1-3 400 x HP positive fields, count positive cell in 200 cells, calculate formula: apoptosis index = apoptosis positive cell amount/total cell a-mount x 100% ) index to reflex apoptosis degree.3. Statistic analysis: statistics adopt 4 factors and 6 variable analysis. Data are expressed as average + SD, inter - group comparison use square differenceanalysis and q test, quantitative martial use chi - square test. ( The above method are all using statistic software SPSS 10.0)Results1. In alcoholic liver group and Acetaminophen group, AST ALT MDA GSH SOD are all increased, AST/ALT >2, GSH is decreased. Different from alcoholic liver and Acetaminophen group, these two groups had significant difference...
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