The Mechanism Of Large-Leaf Yellow Tea On Mice With Specific Hepatic Knockout Prmt1

Tea is abundant in a variety of secondary metabolites,including tea polyphenols,tea polysaccharides,alkaloids,tea pigments,etc.It is involved in the regulation of multiple signal transduction pathways and generates certain pharmacological effects on treating obesity,diabetes,cardiovascular diseases,etc.Using tea as an environmental factor,the effect of tea on epigenetic modification of animal cells was studied.Protein arginine methyltransferase 1(PRMT1)is an essential histone arginine asymmetric methylation-modifying enzyme that normally activates gene transcription.Knockout of mice Prmtl can lead to embryonic lethality.In this group,Prmt1 specific hepatic knockout mice(Prmt1⊿hep)were bred in the early phase to achieve stable genetic inheritance.Prmt1⊿hep mice presented themselves as a liver injury phenotype at the two-month age.To be specific,they are characterized by hepatocyte enlargement,narrower liver sinusoids,irregular arrangement of hepatocytes and varying degrees of vacuolization.This thesis employs Prmt1⊿hep mice as a model and adopts the means of large-leaf yellow tea diet intervention to explore the liver-protection function and regulation mechanism of large-leaf yellow tea as well as to investigate the molecular mechanism of liver-protection function large-leaf yellow tea serves by means of histone modificationThis thesis firstly bred and selected 36 genotype-matched mice and their littermate control mice,which were treated in four groups:respectively control group WT,control group Prmt1⊿hep,tea treatment group WT(WT+5%YTBE),tea treatment group Prmt1⊿hep(Prmt1⊿hep+5%YTBE).The mice were treated with large-leaf yellow tea for 10 months,their growth phenotype was observed and their blood biochemical indicators and liver histology were examined after these mice were dissected.Liver weight ratio,HE staining,oil red staining and β-Catenin immunofluorescence staining experiment results revealed that large-leaf yellow tea could alleviate hepatocyte swelling in Prmt1⊿hep mice,thus reducing liver damage and possessing significant liver-protection effect.In order to further explore its regulation mechanism,we performed experiments such as Western blot,IP,Silver staining,immunofluorescence staining and Real-time PCR.The results demonstrated that large-leaf yellow tea does not affect the expression level of PRMTs family proteins in hepatocytes of Prmt1⊿hep mice,and large-leaf yellow tea does not affect the level of histone methylation in hepatocytes of Prmt1⊿hep mice.After feeding Prmt1⊿hep mice large-leaf yellow tea,the expression of H3K14ac in the livers of Prmt1⊿hep mice grew,the expression of histone acetyltransferases HBO1 increased,reflecting the effects of large-leaf yellow tea on the hepatocytes by means of histone modification.The results demonstrated that the expression levels of Pyroptosis-related proteins(such as Cleaved Caspase 3,Cleaved GSDME)in the livers of Prmt1⊿hep mice decreased significantly after large-leaf yellow tea feeding and maintaining hepatocyte homeostasis,indicating that large-leaf yellow tea could regulate the pyroptosis pathway induced by GSDME.In conclusion,this study utilized Prmt1⊿hep mice as a model to conduct large-leaf yellow tea intervention experiment,which revealed that large-leaf yellow tea does not affect the level of histone methylation in hepatocytes of Prmt1⊿hep mice,increased the level of H3K14ac in Prmt1⊿hep hepatocytes,inhibit the expression of GSDME,regulate the induced pyroptosis pathway through GSDME by means of histone modification and then alleviate the swollen hepatocytes and damaged livers of the Prmt1⊿hep mice so as to achieve their physiological functions of protecting the liver.