| Objective:To prove BMP2 can inhibit the growth of hepatic cell through studying the effects of exogenous Noggin on the regenerating liver and BMP2 after partial hepatectomy(PH) in rats.Metheds: Partial hepatectomy according to Higgins classical methed was performed in 72majority male Wister rats, another 8 as normal control(NC) group.It was conformed that PH was successfully formed .Rats were divided into three groups: normal sodium(NS) group(n=24), low dose Noggin (NL) group (n=24),high dose Nogggin(NH) treatment group(n=24),.The different treatment group were injected with normal sodium (1ml/kg), Noggin (500ng/kg), Noggin (2500ng/kg) before shut bdomina cavityl, repeat it on12,24h after PH. To study the effects of liver regeneration on BMP2 expression ,rats were sacrificed before and at different time points after PH (0,12,48 and 72h),NC group as 0h .For each time point, eight rats were used in parallel.For detecting liver regeneration rate ,weigh all rats before PH and sacrifice ,weigh all livers were cut after PH and sacrifice. Collecte blood in aorta ventralis before sacriice and measure ALT,AST,TGF-α,HA,CG,ALB,AFP in blood serum.BMP2,TGF-α,AFP in regenerating liver homogenate were measured. Liver tissue was fixed by 10% formaldehyde,after paraffin imbedding, BMP2 and PCNA were observed by immunohistochemical staining,hematoxylin and eosin (HE)stain and then analyzed by imaged analysis system..Result:1.The results of liver regeneration:The result of liver regeneration rate: Liver regeneration rate in NH,NL groups were significantly decreased than NS group at 12h after PH(P<0.01). There were no significantly differences among three groups at 48,72h after PH(P >0.05).The result of PCNA in immunohistochemistry: PCNA in all groups were significantly increased gradually than NC group after PH(P<0.01).PCNA in NH,NL groups were significantly decreased than NS group at 12h after PH(P<0.01).There were no significantly difference among three groups at 48,72h after PH(P>0.05).2.The results of liver function:The result of ALT in blood serum: ALT in all groups were significantly increased than NC group at 12h after PH(P<0.01) and returned to normal level at 72h after PH.There were significantly differences among three groups at 12,48h after PH(P<0.01).NL group is highest,NS group is lowest at 12h after PH(P<0.01).NH group is highest,NL group is lowest at 48h after PH(P<0.01).The result of AST in blood serum: AST in all groups were significantly increased than NC group at 12h after PH(P<0.01).AST in NH,NL groups were significantly increased than NS group at 12h after PH(P<0.01).AST in NL group returned to normal level at 48h after PH, AST in NS,NH groups returned to normal level at 72h after PH, but there were no significantly differences among three groups at 72h after PH(P>0.05).The result of HA in blood serum: HA in blood serum in three groups were significantly increased than normal level at 12,48h after PH(P<0.01).This increase was at a peak at 48h and returned to normal level at 72h after PH. There were no significantly difference among three groups at the same time.The result of CG in blood serum: CG in blood serum in three groups were significantly increased than normal level after PH(P<0.01). CG in blood serum in NH,NL groups was significantly increased than NS group at 12h after PH(P<0.05), There were no significantly difference among three groups at 48h,72h after PH(P>0.05).The result of ALB in blood serum: ALB in blood serum in NL group was significantly increased than normal level at 12h after PH(P<0.01) .ALB in blood serum in NS group was significantly increased than normal level at 72h after PH(P<0.01).There were significantly differences among three groups at 12h after PH(P<0.01). There were no significantly difference among three groups at 48,72h after PH.3.The result of TGF-α:The result of TGF-αin liver homogenate: TGF-αin liver homogenate in all groups were significantly increased than NC group at 12h after PH(P<0.01).There were significantly difference among three groups at 12h after PH (P>0.05).TGF-αin liver homogenate decreased after 12h . There were no significantly difference among three groups at 48h after PH (P> 0.05).TGF-αin NH group significantly increased again at 72h after PH(P<0.01).The result of TGF-αin blood serum: TGF-αin blood serum in all groups were significantly increased than NC group at 12h after PH(P<0.01). TGF-αin NS,NH groups were significantly increased than NL group at 12h after PH(P<0.01). There were no significantly difference among three groups at 48h after PH(P>0.05). TGF-αin NS,NL groups was significantly decreased than NH group at 72h after PH(P<0.01). There were no significantly difference between NS group and NL groupt at 72h after PH(P>0.05).4.The result of AFP:The result of AFP in liver homogenate: Liver homogenate AFP in NS group was significantly increased than normal level at 12h after PH(P<0.05). Liver homogenate AFP in NH group was significantly increased than normal level at 48h after PH(P<0.05). Liver homogenate AFP in NL group had no significantly difference after PH (P>0.05).The result of AFP in blood serum: There were no significantly difference among three groups at the same times(P>0.05).5.The result of BMP2:The result of BMP2 in hepatic homogenate:BMP2 in all groups were significantly decreased than NC group at 12h after PH(P <0.01), BMP2 in NH,NL groups were significantly decreased than NS group at that time(P<0.01).BMP2 in NS,NH groups returned to normal level at 48h after PH,BMP2 in NL group returned to normal level at 72h after PH, but there were no significantly difference among three groups at 48h,72h after PH(P>0.05).The result of BMP2 in immunohistochemistry: BMP2 in three groups were significantly decreased than NC group at 12h after PH(P<0.01). BMP2 in NH,NL groups were significantly decreased than NS group at that time(P<0.01).BMP2 in three groups returned to normal level at 48h after PH.The result of BMP2 in blood serum:BMP2 in blood serum in NS,NH groups were significantly increased than NC group at 12h after PH(P<0.01).BMP2 in NS group returned to normal group level at 72h after PH,BMP2 in NH group returned at 48h after PH, but there was no significantly difference between NS group and NH group at the same time(P>0.05).6.The correlating relation between BMP2 in hepatic homogenate and other indexes:At 12h after PH, there was positive correlation between BMP2 in liver homogenate and Liver regeneration rate,PCNA (P<0.01), there were negative correlations between BMP2 in liver homogenate and ALT,AST,CG,ALB in blood serum (P<0.01), there were no correlating relation between BMP2 in hepatic homogenate and HA in blood serum(P>0.05) ,there was negative correlation between BMP2 and TGF-αin liver homogenate (P<0.01), there were no correlating relation between BMP2 in hepatic homogenate and TGF-αin blood serum (P>0.05) ,there was positive correlation between BMP2 and AFP in liver homogenate (P< 0.01), there was negative correlation between BMP2 in liver homogenate and AFP in blood serum (P<0.01),At 48h,72h after PH, there were no correlating relation between BMP2 in hepatic homogenate and other indexes.Conclusion:1.The effect of exogenous Noggin on BMP2: Exogenous Noggin can significantly inhibit BMP2 in regenerating liver in 0～48h after PH.2.The effect of exogenous Noggin on liver regeneration: Exogenous Noggin may indirectly promote liver regeneration by down-regulating effect of BMP2,BMP2 regulae liver regeneration in dose dependent.3.The effect of Noggin on liver function: BMP2 may relieve the hepatic cell injury after PH, exogenous Noggin antagonize the expresson of BMP2 may induce aggravating the hepatic cell injury in the initial stage after PH.4.The effect of BMP2 on AFP:BMP2 can transiently stimulus hepatic cell proliferation at a certion time frame after PH.
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