| Experiments were designed based on the PI3 K insulin signaling pathway in the present study to observe the effect of acupuncture intervention on insulin resistance(IR);OLETF rat,a rat model with spontaneous insulin resistance,as the animal model as well as RT-PCR and Western blot as methods were used to detect the indexes,including fasting blood glucose(FPG),plasma fasting insulins(FINS),C peptide,and cerebrospinal fluid(CSF)insulin,to observe the effect of acupuncture intervention on mRNA and protein levels of IRS-1,IRS-2,PI3 K,Akt,and GSK in the hippocampus of OLETF rats and the content of Aβ and Tau protein in rat hippocampus and cerebrospinal fluid(CSF),therefore,to explore the mechanism of acupuncture in the improvement of IR on the basis of the molecular biology.ObjectiveA rat model with spontaneous insulin resistance,the OLETF rat,was chosen as research subject,and based on which an AD rat model was established.Effect of acupuncture(Baihui,Shenshu,Neiguan,Zusanli and Sanyinjiao as the acupoints)on central IR of AD rats was observed and the effect of acupuncture on the expression of components of the PI3 K signaling pathway in the central insulin signal transduction(IRS-1,IRS-2,PI3 K,Akt,IDE,GSK-3α /β,Aβ,Tau)was preliminarily explored in AD rats,to illustrate the mechanism of acupuncture in the treatment of AD from the perspective of central insulin signal transduction pathway.MethodsOLETF rats with spontaneous IR and LETO rats of the same strain were selected and AD models were established from OLETF rats.The AD model was established by intraperitoneal injection of D-galactose and intragastric administration of AlCl3 solution.The dosages of D-galactose and AlCl3 were 60mg·kg-1·d-1 and 50mg·kg-1·day-1,respectively,and desired volumes of solution were given at the dose of 10ml/kg body weight successively for 90 days.After modeling,the Morris water maze was used for behavioral test and unqualified rats were eliminated.LETO rats were used as the normal control group and the AD model rats were randomly divided into the model group and the acupuncture group,with 8 rats in each group.Animals in the acupuncture group were given acupuncture intervention at acupoints,including Baihui,Shenshu(bilateral),Neiguan(bilateral),Zusanli(bilateral),and Sanyinjiao(bilateral),for continuous treatment of three weeks.At the end of treatment,fasting blood glucose(FPG),plasma fasting insulin(FINS),and serum Cpeptide(C-P),as well as the expressions of IRS-1、IRS-2,PI3K-p85α,Akt,IDE,GSK-3α /β,and Aβ and Tau protein contents in the hippocampus were detected in all rats.ResultsThe levels of FPG,FINS and C-P in the EA-AD-OLETF group with acupuncture intervention were significantly lower than that of the AD-OLETF model group(P<0.01).In the Morris water maze test,percent of time spent in the original platform quadrant in the AD-OLETF model group was shortened compared with that of the normal LETO group(P<0.01);and that of the EA-AD-OLETF acupuncture group was increased compared with the AD-OLETF model group(P<0.05).The results of HE staining showed that after acupuncture intervention,the number of neurons cells in hippocampus was much higher than that of AD-OLETF group,and the cells were obviously improved with regular shape,and arranged more neatly.No apparent changes in the mRNA levels of IRS-1,IRS-2,PI3K-p85α,Akt,IDE,and GSK-3α /β in the hippocampus were noted after acupuncture therapy,while the expression levels of p-IRS-1,p-IRS-2,IDE,and p-GSK-3β proteins were significantly increased(P<0.01,P<0.05)and that of p-PI3K-p85α and p-Akt were decreased(P<0.05)after the intervention compared with that before the intervention.After acupuncture intervention,content of Aβ in hippocampus and cerebrospinal fluid in the EA-AD-OLETF group was significantly lower compared with the AD-OLETF group(P <0.01).The content of Tau protein in the hippocampus of EA-AD-OLETF rats was decreased compared with that of the AD-OLETF group(P<0.01).ConclusionAcupuncture intervention of insulin resistance in the treatment of AD significantly improved the insulin resistance and the cognitive behavior in rat models,promoted the degradation of Aβ,and inhibited the expression of Tau protein.HE staining indicates that acupuncture intervention can improve the damage of nerve cells in hippocampus of model rats,promote the repair of nerve cells,and have obvious improvement effect.In conclusion,it was proposed that effect of acupuncture therapy on the IRS-PI3K-Akt-GSK insulin signal transduction pathway may serves as one of the key links involved in the acupuncture intervention on insulin resistance and AD state,providing new scientific evidence and theoretical basis for the clinical application of acupuncture therapy in the treatment of insulin resistance. |
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