Expression of Toll like receptor 4 in skeletal muscle of type2 diabetic rats and the intervention effect of simvastatin

Abstract

Objective To investigate the expression of Toll like receptor 4 (TLR4) in skeletal muscle of type2 diabetic rats and the intervention effect of simvastatin.Methods The type 2 diabetic rat model was established in 26 SD rats by feeding high-fat,high-sucrose diet and injecting low dose of streptozotocin (STZ).These rats were randomly divided into diabetic group (13 rats) and simvastatin group (13 rats),with 10 normal SD rats as control group.The rats in simvastatin group received simvastatin at a dosage of 20 mg· kg-1 · d-1 by gastric gavage while the ones in normal control group (10 rats) and diabetic group received equal volume of normal saline by gastric gavage.After 8 weeks,fasting blood glucose(FBG),blood lipids and creatine kinase (CK)were measured in all groups,and histological change in skeletal muscle of all rats were observed.The protein and mRNA expression of TLR4 in skeletal muscle was examined by immunohistochemistry staining and RT-PCR respectively.Results FBG of diabetes group and simvastatin group were significantly higher than that of control group [(12.04 ± 2.04) mmol/L,(11.23 ± 2.61) mmol/L vs (5.92± 1.28)mmol/L,all P ＜ 0.05],and there were no significant difference of FBG between diabetes group and simvastatin group.The levels of TG,TC and LDL-C in three groups were diabetes group＞simvastatin group＞control group (all P ＜ 0.05).Levels of HDL-C in three groups were control group＞simvastatin group＞diabetes group (all P ＜ 0.05).There were no significant differences of creatine kinase among three groups.Skeletal muscle of normal control group rats was complete and orderly,muscle fibers arranged in cloes while the morphology of skeletal muscle of diabetic rats was atrophic,fractured and edamed,muscle fiber ruptured and filaments traveling disordered with observed infiltration of inflammatory cells,and such changes were extenuated in simvastatin group.The expression level of TLR4 protein in diabetes group was 1.54 times of control group(0.318±0.037 vs 0.206±0.024,P ＜ 0.05) and level of TLR4 protein in simvastatin group was 80.50％ of diabetes group (0.256±0.035 vs 0.318±0.037,P＜ 0.05).The level of TLR4 mRNA in diabetes group was 1.62 times of control group (0.625±0.074 vs 0.385±0.088,P ＜ 0.05) and level of TLR4 mRNA in simvastatin group was 80.16％ of diabetes group (0.501 ±0.105 vs 0.625 ±0.074,P＜ 0.05).Conclusions Diabetic skeletal muscle lesions is associated with high expression of TLR4.Skeletal muscle lesions may be mitigated by simvastatin through down-regulating TLR4 expression in skeletal muscle. Key words: Diabetes mellitus, type 2; Toll-like receptors 4; Muscle, skeletal; Simvastatin; Rats, Sprague-Dawley