| This study consisted of two parts:the animal experiment and the clinical trial.It aimed at evaluating the effects of oxymatrine(OM),a derivitive from Chinese herbs on severe hepatitis and the hepatocyte apoptosis at its early stage and exploring its mechanisms. Methods: 1 .Animal experiment (1)Fulminant hepatic failure(FHF)was induced by lipopolysaccharide(LPS,0.5 i glkg) intraperitoneally (ip) in D-galactosamine(Ga1N,900mg/kg)sensitized mice. Mice were pretr- eated with three different dosages of OM(25mg/kg,50mglkg and 100 mg/kg, ip.bidX 3d respectively),then were injected with Ga1N/LPS at the 4th day. The study aimed at observing the effects of OM on the survival rate of mice with fulminant heptic failure compared with hepatic stimulating substance (HSS) and selecting the optimal pretreatment dosage of OM. (2)OM and GalN/LPS were administrated as described above. At 7.5h-point after injecting GalN/LPS, mice were sacrificed. The serum were obtained immediately for detecting serum alanine aminotransferase(ALT) and tumor necrosis factor alpha (TNF- a ),the liver specimen for hematoxylin-eosin(I-IE) staining and immunobistochemicaL staining of Fas and its ligand (FasL). (3)OM and Ga1N/LPS were applied as above, At 5h-point after injecting Ga1N/LPS,liver specimen were obtained for the TdT-mediated biotin- dUTP nick end labelling (TUNEL) and observation with the transmi- ssion electron microscope (TEM) beside the same index as stated above, and the effects and mechanisms of OM on the hepatocyte apoptosis at the early stage of fulminant hepatic failure were evaluated. 2.Clinical trial:Sixty five patients with severe hepatitis B(not including the patients with complications of hepatoencephalopathy and bleeding) or chronic active hepatitis B(CAH) were divided into two grou at random: the general therapy group and the general therapy plus OM group (600mgId, intramuscularly).The course of OM administrating was at least half a month. The effects of OM on patients were assessed by observation of survival rate, liver function, blood and urine routine and so on. Results: 1. Animal experiment (1)The mortality of mice with FHF induced by Ga1N/LPS (ip)was about 70%,and the histological features of liver tissue were similar to that in patients with severe hepatitis.The survival rate of mice pretreated with HSS and OM of 25mg/kg, 50mg/kg and 100mg/kg were 40%, 60%, 36.7% and 55% respectively. (2)Compared with model group (at 7.5h- point),the serum levels of ALT and TNF- a in mice of OM group with dosage of 50mg/kg were decreased significantly (P<0.05 and 0.01 respectively).Both the degrees of liver injuries and expression of Fas and FasL in mice of OM group were reduced obviously than that of model group(P<0.01). (3)At Sb- point, the serum level of ALT in OM group was decreased insignificantly compared with the model group,but the serum level of TNF- a in OM group was decreased significantly(P<0.05).As compared with the model group, the mean value of apoptotic cells and expression of Fas and FasL in murine liver of OM group were both reduced obviously(P<0.0l).The characteristic presentation of hepatocyte apoptosis was observed more frequently with TEM in model group than in OM group . 2.Clinical trial: the mortality of patients with severe bepatitis in OM group was 27.8% after mean treatment course of 32d,while it is 35.3% in general therapy group.Both the decline of total serum bilirubin in patients with severe hepatitis and the shorteness of p... |
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