| ANIMAL EXPERIMENTAccording to the basic principles of new drug evaluation before clinic trial recommend by WHO and China State Drug Administration, two different hepatic fibrosis animal models should be adopted in our study. Then, three different doses IFN-y were treated animal fibrosis so as to observ the effect of IFN-y and the relation between different doses and effects. In the meantime, we observed hepatic fibrosis degree in these animals after the treatment stopped.MATERIALS AND METHODSCCl4-induced rat hepatic fibrosis model205 rats were subcutaneously given dissolved CC14 in olive oil (proportion was 4:6) at 0.3 mL/kg of body weight, i.p., for 2 consecutive days a week for 16 weeks. Five rats were killed at the end of each week to examine pathological changes. According to histological sections, hepatic fibrosis emerged at the end of the fourth week from the start of the study.150 rats could be used for the next study. Rats in the two models were divided into five groups, including l).Fibrotic model group, 2).Colchicine treatment group (O.lmg.kg~l.day~ '), gastrogavage), 3).High-dose IFN- Y group (15MU.kg~'.day~1, i.m.), 4). Medium-dose IFN-Y group (SMU-kg-'-day1, i.m.), 5). Low-dose IFN-Y group (I.eTMU.kg-'.day1, i.m.). In addition, 10 rats were chosen to be the normal control group. Rats in the normal control and fibrotic model groups were given 0.9% sodium chloride by intramuscular injection instead of IFN- Y . Rats received 8-week treatment. At the end of the eighth week, 10 rats of each group were killed. Histological sections of liver from the killed animals were evaluated by hematoxylin and eosin and Sirius red stains, a-smooth muscle actin (a-SMA) was examined with imunohistochemistrical technique. Liver hydroxylproline content and serum hyaluronic acid level also were detected. In the next 4 weeks, all treatments stopped. The rest of the rats were killed at the end of the sixteenth week from the start of the experiment.DMN-induced rat hepatic fibrosis model278 rats were injected repeatedly, i.p., for 3 consecutive days at the first week and 2 consecutive days for the next 5 weeks. Five rats were killed at the end of each week to examine pathological changes. According to histological sections, hepatic fibrosis emerged at the end of the fourth week from the start of the study. 196 rats could be used for the next study. Rats in the two models were divided into five groups, including l).Fibrotic model group, 2).Colchicine treatment group (O.lmg.kg'1.day1), gastrogavage), 3).High-dose IFN- Y group (15MU.kg''.day"1, i.m.), 4). Medium-dose IFN- Y group (5MU.kg-'.day', i.m.), 5). Low-dose IFN- Y group (1.67MU.kg-'.day', i.m.). In addition, 10 rats were chosen to be the normal control group. Rats in the normal control and fibrotic model groups were given 0.9% sodium chloride by intramuscular injection instead of IFN-Y. Rats received 4-week treatment. At the end of the fourth week, 10 rats of each group were killed. Histological sections of liver from the killed animals were evaluated byhematoxylin and eosin and Sinus red stains, a-smooth muscle actin (a-SMA) was examined with imunohistochemistrical technique. Liver hydroxylproline content and serum hyaluronic acid level also were detected.Histological study.The Sinus red stain method was used to specifically stain fibrous tissue components. These sections were observed under polarization microscopy to distinguish type I and III collagen. A single pathologist who graded and scored the specimens according to the criteria of Scheuer and Chevallier et al reviewed specimens under code. In Scheuer criteria, the transformation of grade and stage was as follows: stage 0, = 2? grade or stage 1, = 21; grade or stage 2, = 22; grade or stage 3, = 23; grade or stage 4, = 24. In the meantime, a single pathologist who graded and scored the specimens according to Wang BE et al reviewed specimens under code.Identification of activated hepatic stellate.a-SMA, a marker of activated hepatic stellate (HSC), was detected in for...
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