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Phellinus Linteus Intervention Effect On Diabetic Rats And Skeletal Muscle Transcriptomics Analysis

Posted on:2021-05-01Degree:MasterType:Thesis
Country:ChinaCandidate:C R WangFull Text:PDF
GTID:2404330611483363Subject:Microbiology
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Diabetes mellitus is a common metabolic disease,often accompanied by atherosclerosis and other complications,which seriously threatens human health.Among patients with diabetes,type 2 diabetes accounts for 95%."Sanghuang" is a rare medicinal fungus.According to historical records,it has immunomodulatory and blood glucose control effects,but its application in contemporary times is very limited.In this study,the solid fermented Phellinus linteus mycelium water extract(hereinafter referred to as PLE)was used as a material to perform an 8-week PLE gavage intervention experiment on type 2 diabetes mellitus(T2DM)rats.Transcriptome sequencing and data analysis were performed on skeletal muscle samples.The following conclusions are obtained:(1)Use a low-dose STZ injection in combination with a high-fat diet to establish a stable T2 DM rat(SD)model.After 8 weeks of PLE intragastric intervention,it was shown that PLE can effectively alleviate diabetic symptoms such as "overeating",weight loss and elevated blood sugar in T2 DM model rats.(2)The detection of serum insulin and the calculation of the insulin resistance index found that PLE can significantly reduce the fasting insulin content and alleviate the level of systemic insulin resistance;PLE intervention can adjust the abnormal metabolism of muscle glycogen and make the muscle glycogen level close to normal.mouse.Furthermore,OGTT and ITT tests were conducted on rats in each group,and it was found that PLE can partially alleviate the impaired glucose tolerance of T2 DM rats and increase the sensitivity to insulin.(3)The detection of oxidative stress levels and inflammatory response markers in skeletal muscles of rats found that the intervention of PLE increased the content of SOD enzymes in skeletal muscles of T2 DM rats and reduced the accumulation of MDA by about 30%;The intervention also significantly reduced the levels of TNF-? and IL-6inflammatory factors in the skeletal muscle of T2 DM rats.(4)RNA-Seq sequencing and analysis of skeletal muscle samples showed that there were 216 differentially expressed genes that were significantly changed by T2 DM and rescued by PLE.Functional analysis of differentially expressed genes found that the intervention of PLE at the transcription level alleviated the degree of expression of glucose and lipid metabolism abnormalities and oxidative stress and inflammation caused by T2 DM.(5)Western blot to verify the phosphorylation levels of Akt and Fox O1 proteins in the Akt / Fox O1 signaling pathway,and the relative expression of glucose transporter Glut4,indicating that the gene expression levels in the transcriptome are basicallyconsistent,indicating that PLE intervention has alleviated The insulin signaling pathway caused by T2 DM is impaired.At the same time,the expression levels of My HC-I and My HC-IIb marker proteins of different muscle fibers were detected,indicating that the intervention of PLE increased the content of type I slow muscle fibers in skeletal muscle,decreased the content of type IIb fast muscle fibers,and there was a conversion between muscle fiber types.The results of this study provide a theoretical reference for the development and application of Phellinus linteus extract as a potential hypoglycemic drug.
Keywords/Search Tags:Phellinus linteus extract, Type 2 diabetes mellitus, Insulin resistance, RNA-Seq, Skeletal muscle fiber type conversion, Akt/FoxO1 pathway
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