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The Effect Of Five Species Of Dendrobium On Mice Liver Cytochrome P450 Enzyme Expression And Its Protective Effect On Liver Injury

Posted on:2018-06-30Degree:MasterType:Thesis
Country:ChinaCandidate:K WangFull Text:PDF
GTID:2334330533459553Subject:Pharmaceutical Engineering
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Dendrobium is a perennial herb of Orchidaceae,It is a rare traditional Chinese medicine in our country and has been used for thousands of years.It has numerous pharmacological effects such as antioxidant?anti-tumor and enhanced immunity.Currently,it has been reported that Dendrobium huoshanense has protective effect on alcoholic liver injury,however,there is no literature report on the hepatoprotective effect of different Dendrobium species on different liver injury models.Therefore,this study selected five different Dendrobium species: Dendrobium huoshanense?D.officiale?yunnan??D.officiale?huoshan?? D.henanense and D.moniliforme,and through the establishment of two models of acute liver injury,the liver activity of Dendrobium and the comparative study of different species of Dendrobium hepatoprotective effect were evaluated,with the view to rationalize the use of Dendrobium to provide experimental basis.In addition,the effects of Dendrobium on the expression of cytochrome P450 protein was studied,which provided reference for clinical safety on the usage of Dendrobium.The main contents and conclusions are as follows: 1.Effects of five species of Dendrobium on the expression of P450 enzyme protein in mice liver.Western blot was used to determine the effect of five species of Dendrobium on the expression of 8 major cytochrome P450 enzymes in mice liver.At the same time,the safety evaluation of Dendrobium was carried out to investigate whether Dendrobium was toxic in this experiment.The results showed that the expression of CYP1A1?CYP1A2 and CYP2 E protein was significantly induced by Dendrobium huoshanense;The expression of CYP2A?CYP2B? CYP3A?CYP2C19 and CYP2 E protein was significantly induced by D.officinale?yunnan?;The expression of CYP2 A protein was significantly induced by D.officinale?huoshan?;The expression of CYP1A1?CYP2A?CYP2B and CYP2D6 were inhibited by D.henanense;The expression of CYP1A1 and CYP3 A protein was significantly induced by D.moniliforme.Furthermore,Serum biochemical ?viscera index and histopathological results showed that the mice in the Dendrobium administration group did not produce any damage compared with the normal control mice.It is safe and non-toxic to take Dendrobium under the dose used in this experiment.2.Hepatoprotective effects of five species of Dendrobium on CCl4-induced liver injury in mice.CCl4 acute liver injury model is a commonly used liver injury model,the damage mechanism is related to lipid peroxidation.This chapter established a CCl4 acute liver injury model to evaluate the hepatoprotective effect of five Dendrobium.The results showed that Dendrobium decreased the levels of alanine aminotransferase?ALT?and aspartate aminotransferase?AST?in the serum,increased superoxide dismutase?SOD?activity in mice liver tissue in different degrees and inhibited the overexpression of malondialdehyde?MDA?.Moreover,the pathological damage of liver tissue was effectively relieved.Among the different regions and different species of Dendrobium showed different hepatoprotective effect,with Dendrobium huoshanense recording the best hepatoprotective activity.3.Hepatoprotective effects of five kinds of Dendrobium on acetaminopheninduced liver injury in mice.Acetaminophen?APAP?is commonly used in clinical practice to relieve analgesia,but long or large doses can cause liver damage,it is generally believed that APAP liver injury in the metabolic process is irreversibly associated with macromolecules caused.To evaluate the effect of Dendrobium on hepatic injury induced by different mechanisms,this chapter uses APAP as the source of liver injury induction to establish an acute liver injury model in mice.The results showed that compared with the model group,the Dendrobium administration group has effectively improve the activity of serum ALT and AST in mice and the contents of glutathione?GSH?and SOD in liver tissue,while the MDA content was significantly reduced.The liver prorective mechanism may be: to improve the antioxidant enzyme activity,and enhance the body's antioxidant ability to inhibit lipid peroxidation.Different Dendrobium showed different liver activity,However,the liver protective effect of Dendrobium huoshanense was the best.4.Effects of Dendrobium huoshanense antagonism on inflammatory factors in CCl4-induced liver injury.In order to evaluate whether the hepatoprotective mechanism of Dendrobium was related to the inflammatory response,interleukin-1??IL-1??? interleukin-6?IL-6?and tumor necrosis factor-??TNF-??mRNA levels in the liver were measured by Real-time PCR.At the same time,the expression of protein was detected by immunohistochemistry.The results showed that Dendrobium huoshanense could decrease the expression of inflammatory factors in mice liver.
Keywords/Search Tags:Dendrobium, cytochrome P450, carbon tetrachloride, acetaminophen, liver injury
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