Relationship Between Caveolin-1, TLR4, And MiR-107 In Diabetic Peripheral Neuropathy Animals

Objective:1.To discuss the relationship between Cav-1,TLR4,miR-107 in type 1 diabetic rats with peripheral neuropathy.2.To establish a type 2 diabetic mouse model with peripheral neuropathy using high fat diet plus mild dose of streptozotocin(STZ).Methods:1.Rats were intraperitoneally injected with 65 mg/kg 1%STZ,fed for 4 weeks and several physiological parameters were measured.The L4-L6 spinal cord(SC)and dorsal root ganglia(DRG)were harvested and monocytes from peripheral blood mononuclear cell were collected using histopaque 1083 at week 4.The expression level of miR-107 were measured using qRT-PCR.Expression level of protein TLR4,MyD88,NF-?B p65,Cav-1 were measured using Western Blotting.IL-1? were measured using ELISA.2.Mouse were intraperitoneally injected with 120mg/kg 1%STZ,fed with high fat diet for 24 weeks,and several physiological parameters were measured.The oral glucose tolerance test were performed at week 12.Mouse skin from hind paw were collected for intra-epidermal nerve fiber density(IENFD)at week 24.Plasma insulin were measured using ELISA for the homeostasis model assessment of insulin resistance(HOMA-IR)calculation.Results:1.Compared with the control group,the type 1 diabetic rat with DPN experienced significant blood glucose elevation,weight loss,mechanical and thermal threshold hypoalgesia,and IENFD decline compared with the control group at week 4(P<0.05).Plasma IL-1? level were significantly upregulated(P<0.01),Monocyte TLR4,MyD88,Nf-?B p65,Cav-1,and miR-107 level were significantly upregulated(P<0.05).TLR4,Cav-1,miR-107 level from SC and DRG were not significantly expressed.2.Mouse fed with high fat diet and intraperitoneal injection of STZ experienced significant elevation of oral glucose tolerance test at week 12,and significant upregulation of random glucose,HOMA-IR at week 24(P<0.05);and also experienced significant loss of mechanical threshold and IENFD compared with the control group at week 24(P<0.05).Conclusion:1.At week 4,the TLR4-MyD88 signaling pathway were activated in type 1 diabetic rats with DPN during inflammation,along with upregulation of Cav-1 and miR-107.The TLR4-MyD88 signaling pathway were not activated in L4-L6 SC and DRG,nor did activation/upregulation of Cav-1 and miR-107.2.Mouse model of type 2 diabetic mellitus with DPN was successfully established with IENFD decline at week 24.