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Study On The Mechanism Of Electroacupuncture Regulating Skeletal Muscle Endoplasmic Reticulum Stress IRE1/JNK To Improve Insulin Resistance In T2DM Rats

Posted on:2021-04-05Degree:MasterType:Thesis
Country:ChinaCandidate:Y Z JinFull Text:PDF
GTID:2434330632955689Subject:Acupuncture and Massage
Abstract/Summary:PDF Full Text Request
Significance:Type 2 diabetes mellitus(T2DM)is a chronic metabolic disease characterized by hyperglycemia and accompanied by insulin resistance(IR)or relative insulin secretion disorders.Among them,IR runs through all stages of the course of T2DM and plays an important role in the occurrence and development of the disease.The occurrence of IR mainly involves skeletal muscle,fat and liver tissue.Among them,skeletal muscle takes up about 80%of glucose,which is an important tissue to maintain a constant blood sugar balance and utilize glucose,so skeletal muscle plays a vital role in IR.Diabetes is a major problem facing public health,and has been identified as a major disease of metabolic diseases.Acupuncture therapy is a non-drug therapy,one of the traditional Chinese medicines,and has proven its efficacy through clinical and experimental research.Weiwanxiashu,Pishu,Zusanli,Sanyinjiao are commonly used points for T2DM,so this study explores the mechanism of electro acupuncture intervention on insulin resistance and glucose lowering,which is of great significance to the study of T2DMObjective:This study is based on the endoplasmic reticulum stress of T2DM research hotspot,which activates c-Jun N terminal kinase(JNK)from inositol requiring enzyme 1(IRE1)to affect phosphatidyl inositol 3-hydroxy kinase(PI3K),spontaneous type 2 diabetic rats were used as the research objects to observe the fasting blood glucose(FBG),oral glucose tolerance test(OGTT)area under curve(AUC),blood lipid,homeostasis model assessment-insulin resistance(HOMA-IR),insulin sensitivity The index(ISI).and from IREI,JNK,p-JNK,insulin receptor substrate-1(IRS-1)ser307,PI3K p85,glucose transporter 4(GLUT4)protein expression level analysis of the mechanism of electro acupuncture to improve insulin resistanceMethods:14 SPF male zucker diabetic fatty(ZDF)rats(fa/fa)with a body mass of 140-1 60g(2 months old)were selected and randomly divided into a model group and an electro acupuncture group;another 7 rats of the same month SPF grade male zucker diabetic lean(zucker lean,ZL)rats(fa/+)were used as blank group.After modeling,fasting blood glucose and OGTT of each group were measured,and the intervention was continued for 4 weeks(Monday to Saturday),and fasting blood glucose and OGTT were measured on the second day of the last intervention.After intervention,serum triglyceride(TG),total cholesterol(TC),high density lipoprotein(HDL),low density lipoprotein(LDL),and very low density Lipoprotein(vLDL)content,and analyze the effect of electro acupuncture on blood lipids,take the rat quadriceps muscle,Western Blot method to detect IRE1,JNK,p-JNK,IRS-1 ser307,PI3K p85 in skeletal muscle,GLUT4 expression level,verify whether electro acupuncture improves IR by regulating endoplasmic reticulum stress and PI3K signaling pathway.SPSS21.0 was used for statistical analysis.Results:In the experimental results,all ZDF rats' high-sugar and high-fat diet showed a significant increase in FBG one month after induction,and during the experiment,ZDF rats'dietary intake and oral glucose tolerance were abnormal.After 4 weeks of intervention,FBG in the electro acupuncture group was lower than that in the model group(P<0.05),indicating that electro acupuncture can reduce FBG.After 4 weeks of electro acupuncture intervention,OGTT AUC partly decreased compared with the model group,but the difference was not statistically significant(P>0.05).The levels of HOMA-IR and ISI in the electro acupuncture group were significantly lower than those in the model group(P<0.05),indicating that electro acupuncture can reduce insulin resistance.There was no statistically significant difference between vLDL and LDL levels in the three groups;after 4 weeks of electro acupuncture intervention,serum TC,TG,HDL content decreased slightly compared with the model group,but the difference was not statistically significant.Studies on the mechanism of electro acupuncture intervention to improve insulin resistance showed that the expression of IRE1,JNK,and p-JNK protein in the electro acupuncture group was significantly lower than that in the model group(P<0.05,P<0.01),indicating that electro acupuncture can control endoplasmic reticulum stress.The expression of IRS-1 ser307 protein in the electro acupuncture group was significantly lower than that in the model group(P<0.01),and the expression of PI3K p85 and GLUT4 protein in the electro acupuncture group was significantly higher than that in the model group(P<0.01),indicating that electro acupuncture can regulate endoplasmic reticulum stress Alleviate the overexpression of IRS-1 ser307 and increase the expression of PI3K p85 and GLUT4.Conclusion:Electro acupuncture of Weiwanxiashu,Pishu,Zusanli and Sanyinjiao intervention for 4 weeks can reduce the levels of FBG,HOMA-IR and ISI in spontaneous type 2 diabetic rats,thereby improving the symptoms of insulin resistance and abnormal glucose metabolism.At the same time,electro acupuncture can control the endoplasmic reticulum stress IRE1/JNK,inhibit the overexpression of IRS-1 ser307,restore the normal transduction of insulin,and up-regulate the expression of PI3K p85 and GLUT4,so as to achieve the mechanism of improving insulin resistance and lowering blood sugar.
Keywords/Search Tags:Electro acupuncture, type 2 diabetes mellitus, insulin resistance, skeletal muscle, endoplasmic reticulum stress
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