| Objective：The prevalence of diabetes mellitus （DM） was rising year byyear with the improvement of people’s lives and changes of life style. As theworld’s most populous country, China has diabetic patients accounted forone-third of those in the world. As early as one survey in2008has showedthat the prevalence of diabetes in20years of age or older in Chinese was9.7%,and90%of them were type2diabetes mellitus （T2DM） which characterizedby insulin resistance （IR）. The chronic complications of type2diabetesmellitus can be widely involved in the cardiovascular system, nervous system,kidney, liver, skeletal muscle, etc. Diabetic skeletal muscle lesions, whichcharacterized by muscle fiber atrophy and muscle volume decreases, wasspecific chronic complications of diabetes mellitus. Its main clinicalsymptoms were muscle weakness, pain, muscle atrophy, etc. Toll-like receptor4（TLR4） was one of the members of the family of TLRs which was related toinsulin resistance and was conjectured which involved in type2diabetesmellitus and complications. Simvastatin was one of the eutherapeutic lipiddrugs, which was shown that it also had some functions like anti-inflammation,oxidation resistance and anti-atherosclerosis in recent years. In this research,rat model of type2diabetes mellitus was repeated. Through detecting theexpression of TLR4in skeletal muscle of type2diabetic rats with or withoutsimvastatin to discusses the relationship between TLR4and diabetic skeletalmuscle lesions and to observe the effect of simvastatin on diabetic skeletalmuscle lesions.Methods: Forty healthy male SD rats （6-week-old, weight180g±20g）were randomly assigned to normal control group （n=10） and test group （n=30）after adaptive feeding for1week. Control group rats were fed with normalfood while test group rats were fed with high-fat and high-sucrose diet and then were injected streptozotocin （STZ） at a dosage of30mg·kg-1in4weeksfor production of type2diabetes model. Then the diabetic models wererandomly divided into diabetes group and simvastatin intervention group. Therats in intervention group were given simvastatin at a dosage of20mg·kg-1·d-1for8weeks while the ones in control group and diabetes groupwere received the equal volume normal saline. At the end of the experiment,the rats were executed to collect blood and skeletal muscle sample.Biochemical indicators of blood serum were detected such as fasting bloodglucose （FBG）, triglyceride （TG）, total cholesterol （TC）, low-densitylipoprotein cholesterol （LDL-C）, high-density lipoprotein cholesterol（HDL-C）, creatine kinase （CK）, etc. The protein and mRNA expression ofTLR4in skeletal muscle was measured by immunohistochemistry staining andRT-PCR respectively. The data was dealt with SPSS19.0.Results:1The general situation of the ratsThere were no obvious changes in control group rats on diet and urinevolume and the body weight increased gradually. The rats in diabetes groupand simvastatin group performed urine volume, drinking and appetiteincreased but weight declined gradually. Some of them appeared cranky orslow response, listlessness, less active.2Biochemical indexes of the rats2.1Indexes of the sixth weekendFBG of test group was higher than that of control group while thedifference of FINS between the two groups was not statistical significant.Compared with control group, ISI in test group was decreased significantly.2.2Indexes of the fourteenth weekendFBG of diabetes group rats and simvastatin group rats were higher thanthat of control group rats, and the FBG between the fist two groups had nostatistical discrepancy. Difference of creatine kinase among groups was notstatistically significant. TG, TC and LDL-C of diabetes group rats andsimvastatin group rats were higher than those of control group rats, and the indicators in simvastatin group were lower than those in diabetes group.HDL-C was opposite, yet.3Morphology of skeletal muscleSkeletal muscle of normal control group rats was complete and orderlywithout inflammatory cells infiltrated. While the morphological changes of thediabetic rats were atrophic, fractured and disordered, and it was a littleremitted in simvastatin group rats.4The expression of TLR4protein in skeletal muscleImmunohistochemistry results showed that there were many claybankparticles on the membrane of skeletal muscle, and the cytoplasm alsoexpressed a little. Compared with control group rats, the expression of TLR4in skeletal muscle significantly increased in diabetes group and simvastatingroup. And it was decreased in simvastatin group than that in diabetes group.5The expression of TLR4mRNA in skeletal muscleThe TLR4mRNA in skeletal muscle of simvastatin group rats was higherthan that in control group but lower than that in diabetes group. The differenceamong groups had statistical significance.Conclusions:1Diabetic skeletal muscle lesions may be related to high expression ofTLR4in skeletal muscle.2Skeletal muscle lesions may be lessened by simvastatin throughdown-regulating TLR4expression in skeletal muscle. |
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