Effects Of Silibinin On Oncosis In D-galactosamine Induced Acute Hepatic Injury In Rats

Background:The oncosis is another death mode of cells,which quite distinct from apoptosis.It can be observed in various processes of physiology and pathology.The characteristic morphology of oncosis shows that cell swelling,plasmolysis and vacuole can be watched.The mitochondria were swelled and the crista was reduced.Whereafter the nueleolus appeared molten lacunae.The construction of nucleus was vague,more euchromatin,less heterochromatin.Liver is not only the central digestive organ but also the critical metabolizable organ,which has the ruction of digestion,absorbability,metatbolism, excretion,detoxifcation,hemopoiesis and immunoreaction.Hepatic injury is the common liverish approach.If being continual in existence it can lead to the liver fibrosis,even to hepatocirrhosis and liver cancer.So it is a pivotal hinge to prevent liver from injuring.Since the nineties of the twentieth century,the investigation of hepatic injury has being lucubrated increasingly.Rencently,the oncosis was found has a critical roll in hepatic injury.Silibinin (SIL) is the most component of silymarin.As an antioxidant,SIL plays an important roll to protect the liver against attack.At the same time,SIL has many officinal effects.It can eliminate reactive oxygen species(ROS),to counteract lipid peroxid,inhibit nitric oxide synthesis/5-lipoxygnase(5-LOX) and hepatic fibrosis,promote repair and ripeness of hepatocytes,regulate immunity,increase glutathione(GSH),restrain tumor,reduce the blood lipid,and so on.But the effects of silibinin on oncosis in D-galactosamine(D-GalN) induced acute hepatic injury is absent.The substantial mechanism is unbeknown.Objective:To explore the effects of silibinin on oncosis in D-galactosamine(D-GalN) induced acute hepatic injury and its mechanism,to provide some experiment basements for the clinical use of SIL,furthermore to found new more method and idea at liverish therapy points.Methods:The 60 SD rats were randomly divided into control group(n=12),model group(n=24)and SIL pretreated group(n=24).The model group and SIL pretreated group were established by D-GalN intraperitoneal injection.The rats were executed after injured 4h/8h/12h/16h/20h/24h.To evaluates the hepatic injury,the serum alanine aminotransferase (ALT) and aspartate aminotransferase(AST) were detected by automatic biochemistry analyzer.The histopathology was observed by light microscope and transmission electron microscope(TEM).The expression of nuclear factor-κB(NF-κB)was detected by immunohistochemistry and the tumor necrosis factor-α(TNF-α)was detected by reverse transcription polymerase chain reaction(RT-PCR).The oncosis index was detected by TEM.Results:1.The level of ALT and AST:After injured 4 hours,the level of ALT and AST in model group was significant higher than control group(P＜0.05).The level worked up along with the phase,and got a peak after 20 hours(ALT,1544.5±336.62;AST,2341.25±433.01).Compared to model group in each phase,the level of ALT and AST in SIL pretreated group was lower(P＜0.05).2.The histopathology characters and the detection of oncosis:Under light microscope, in model group the construction of liver tissue was disturbed.The limiting plate of liver was disappeared.A large of hepatocyte was necrosised,and inflammatory cells infiltrated into tissue.But in SIL pretreated group the construction of liever was complete.The endochylema showed vacuole,a small amounts of inflammatory cells infiltrated.Under TEM in model group,oncoctic change-which showed cell swelling,membrane partly expand outward,kytoplasm vaeulization,endocytoplasmic reticulum and crista swelling, chromatin dissipation or integrate-can be watched at 4h and the OI added while the time is later.In SIL pretreated group,we found the OI was lower than model group(P＜0.05).3.The expression of NF-κB:In control group,NF-κB was little expressed or only expressed in plasma.In model group,the expression of NF-κB was strengthened,and transferred from plasma to nucleus,then got a peak after 4 hours(38.36±4.75%).In SIL pretreated group,the expression was positive in different degree,but was lower than model group(P＜0.05).4.The expression ofTNF-αmRNA:In control group the expression was trace amount. In model group,the expression was enhanced and got a peak after 4h.In SIL pretreated group,the expression was lower than model group(P＜0.05).Conclusion:1.Acute hepatic injury can be induced by D-GalN,in this model,the levels of ALT and AST in serum were significant increased,the expression of NF-κB and TNF-αwere enhanced.And the oncosis were observed.2.SIL can inhibit the expression of NF-κB and TNF-αin liver tissue.3.SIL can decrease the oncosis and control the level of ALT/AST and OI in D-GalN induced acute hepatic injury in rats,its mechanism might be related to the expression of NF-κB and TNF-α.