| Part1Establishment and evaluation of rats model of hepatic sinusoidal obstruction syndrome induced by gynura segetumObjective:To establish and evaluate rats model of hepatic sinusoidal obstruction syndrome(HSOS) induced by gynura segetum for further research on treatment and pathogenesis.Methods:30adult SpragueDawley(SD) rats were randomly divided into2groups of gynura segetum and control,they were gavaged with gynura segetum decoction and warm warter.4weeks later,all the rats were killed,blood samples were collected for testing liver function and blood cell counts,liver tissues were collected for HE staining and Masson staining, pathological changes were assessed by Deleve scoring system.Results:1.All the rats in gynura segetum group developed HSOS,but the control group didn’t.2.Compared with the control group, rats in gynura segetum group showed increased the count of white blood cell (WBC) and significantly decreased the count of red blood cell(RBC) and platelet(P<0.05).3.No body weight difference showed between the two groups,but liver weight and liver ratio(liver weight/body weight) in gynura segetum group obviously increased(P<0.05)4.Compared to the controls,liver functions including serum alanine transaminase(ALT)、aspartate transaminase(AST)、total bilirubin(TBIL)、 direct bilirubin (DBIL) in rats with HSOS increased, but albumin decreased,the differences were statistically significant(P<0.05).5.According to Deleve standard,liver pathologics changs in gynura segetum group were almost moderate or severe.Conclusions:Rat model with HSOS were successfully induced by gynura segetum, and the pathologic severity was consistent with clinic findings.It means that gavaging with gynura segetum could provide stable and reliable rats models with HSOS for further study. Part2Therapeutic effect of prednisone on rats model of hepatic sinusoidal obstruction syndrome induced by gynura segetumObjective:To investigate the therapeutic effect of different dose of prednisone on rats model of hepatic sinusoidal obstruction syndrome induced by gynura segetum.Methods:60adult male SD rats were randomly divided into two groups, normal control group(group A)and gynura segetum group, they were gavaged with warm warter and gynura segetum decoction.4weeks later, the gynura segetum group were randomly divided into modeled control group(warm water,group B), low dose of prednisone group (4mg.kg-1.d-1group C),high dose of prednisone group (Pmg.kg-1.d-1group D),4weeks later all the rats were killed, blood samples were collected for testing blood cell counts、 liver function and plasminogen activator inhibitor-1(PAI-1),liver tissues were collected for HE staining and Masson staining, pathological changes were assessed by Deleve scoring system.Results:1.Compared with group B, ALT、AST、TBIL and DBIL in group C and D decreased (P<0.05); the index had no significant differences between group C and D; statistical differences between treated group(group C and D)and normal control group remained(P<0.05).2.PAI-1results:The value in treated group(group C and D) was lower than that in group B, especially difference between B and C was obvious, but it was still higher than group A (P<0.05), no statistical difference between group C and D.3.Pathologic results:according to Deleve scoring system, no HSOS was in group A,ratio in group B is3:8:5(severe:moderate:mild),compared to3:3:8in group C (1normal) and4:2:8in group D.4.The value of PAI-1in serum was consistent with hepatic pathological score.Conclusions:1.Prednisone had certain therapeutic effect in rats model of HSOS induced by gynura segetum including improvement in liver function and liver pathological conditions, but in the experiment dose range, it showed no obvious dose-effect relationship.2.The uniformity of the value of PAI-1in serum and hepatic pathological score suggests that the index could be an index for monitoring the severity of HSOS and therapeutic effect. Part3The possible therapeutic mechanism of prednisone on rats model of hepatic sinusoidal obstruction syndrome induced by gynura segetumObjective:To explore the possible therapeutic mechanism of prednisone on rats model of hepatic sinusoidal obstruction syndrome induced by gynura segetum by means of measuring the expression of endothelin-1(ET-1)、inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS).Methods:60adult male SD rats were randomly divided into two groups, normal control group(group A)and gynura segetum group, they were gavaged with warm warter and gynura segetum decoction.4weeks later, the gynura segetum group were randomly divided into modeled control group(warm water,group B), low dose of prednisone group (4mg.kg-1.d-1group C),high dose of prednisone group (9mg.kg-1.d-1group D),4weeks later all the rats were killed, Western Blot were used to measure the mRNA and protein expression of ET-1、iNOS and eNOS in liver tissues.Results:Protein expression of ET-1, iNOS, eNOS:compared with group A,mRNA of ET-1、iNOS、eNOS were significantly increased in group B、C and D(P<0.05);in comparismn with group B,3indexs in group C and D all decreased (P<0.05), the index had no significant differences between group C and D.Conclusions:Prednisone exerts its therapeutic effect on rats with HSOS improving microcirculation by the possible way of down-regulating vasoactive factor (ET-1,iNOS,eNOS)... |
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