Expression Of ENOS And INOS In Liver And Intestines In The Forming Of Hepatic Cirrhosis And Significance

Objectives:To investigate the expression of endothelial nitric oxide synthase and inducible nitric oxide synthase in live and intestine tissue of the hepatic cirrhosis and the correlation of their genesis with IETM,thus further to identify the function of NOS-NO system in the forming of hepatic cirrhosis.Methods:The experiment(Exp)1.The animal of male wistar rats were divided randomly into three groups,normal contral(NC)group was treated with normal diet;hepatic fibrosis(HF)group and the hepatic cirrhosis group(HC)which were treated by composite factors(injected CC14 at hypodermis,feeded with high lipoids,high cholesterin and alcohol).The stages of hepatic fibrisis are defined by staining haematoxylin-eosin(HE)and van gieson(VG).The levels of peripheral plasma endotoxin(ET),alanine aminotransferase(ALT),malondialdehyde(MDA),superoxide dismutase(SOD)and the levers of liver homogenate NO,MDA and SOD were detected.The expressions of endothelial nitric oxide synthase(eNOS)and inducible nitric oxide synthase (iNOS)in liver were observed by the method of immunohistochemistry.Exp 2.The animal and groups were the same as Exp 1.The mark of the pathological damage in intestine was given by staining HE.The levels of peripheral plasma ET,portal plasma ET,peripheral plasma tumor necrosis factorα(TNF-α)and the levers of intestinal homogenate NO,MDA and SOD were detected.The apoptosis of endothelial cell in intestinal mucous membrane was observed by TUNEL method.The alter of ileal ultrastructure was observed by electron microscope.Results:1.The modeling of the hepatic cirrhosis of rats:It was confirmed that 4 weekend was the stage of hepatic fibrosis and 8 weekend was the stage of hepatic cirrhosis by both the liver HE and VG.2.The detected results of plasma ET,ALT and TNF-α:The levels of plasma ET,ALT and TNF-αin HF and HC groups were higher than those in NC group.There was a statistics difference existing between groups of model and control,P＜0.05.3.The detected results of MDA and SOD:The results of plasma and homogenate MDA showed a tendency to increase in model groups compared with the NC group.The result of SOD in control normal group was lower than that in model groups.There was a statistics difference existing between groups of model and control, P＜0.05. 4.The results of homogenate NO and the expression of eNOS and iNOS:The liver and intestine homogenate NO in HF group and HC group were higher than that in NC group.There was a statistics difference existing between groups of model and control,P＜0.05.In liver tissue,the expression of eNOS and iNOS in model groups were much higher than those in NC group.In intestine tissue,the expression of eNOS showed a tendency to decline but iNOS showed a tendency to increase in NC,HF and HC groups.There was a statistics difference existing between groups of model and control,P＜0.05.5.The apoptosis of endothelial cell in intestinal mucous membrane:The apoptotic index of intestinal mucous membrane endothelial cell was gradually heightened in NC,HF and HC groups.There was a statistics difference existing among every group,P＜0.05.6.The results of intestine HE and electron microscope:There was distinct pathological change in model groups compared with the NC group and the HC group was the severest.7.The results of correlation analysis:(1)The results of correlation analyses between plasma ET and liver homogenate NO,liver eNOS, liver iNOS and plasma MDA are respectively positive correlation.(2)The results of correlation analyses between plasma ET,TNF-αand the apoptotic index of intestinal mucous membrane endothelial cell are respectively positive correlation.(3)The result of correlation analysis between intestinal iNOS and apoptotic index is positive correlation.Conclusion:1.The forming of hepatic cirrhosis of rats accompanies IETM.The forming of IETM is related with NO.2.Both eNOS and iNOS can express in the condition of hepatic fibrosis and hepatic cirrhosis, which may be concerned with the inducing of endotoxin.3.Intestinal NO can intensify IETM by damaging intestinal barrier.The expression of iNOS is concerned with the inducing of endotoxin.In conclusion,we can consider that endotoxin can induce the expression of iNOS and eNOS in liver and intestines.Because of the production of NO,it can intensify the increase of endotoxin.Thus infernal circle is formed.