| Objective: The diabetic macrovasculopathy is one of chronic complications and the main cause to attribute the death and physical deformity in patients with T2DM. Atherosclerosis is the most important pathological change of diabetic macrovasculopathy. Recent studies have shown that Cathepsin S (Cat S) is a major protease which can dissolve the extracellular matrix to promote the development of atherosclerosis. In this study, the animal model of diabetes was used to research the relationship of diabetic atherosclerosis with Cat S, and the role ofα-lipoic acid in affecting the expression of Cat S in diabetic aorta.Methods:(1) 21 male SD rats were randomly divided into two groups: normal control group of 9 rats and STZ induced diabetic group of 12 rats. The aorta samples were obtained after 4 weeks, which were used to observe the general structure of the aorta by HE staining and the Cathepsin S expression in artery using the DNA microarray.(2) 5 Wistar rats as normal control group and 5 Goto-Kakisaki rats as type 2 diabetic group were fed with high-fat diet. After 12 weeks, the aortas were obtained and embedded in paraffin. HE staining was used to observe the general structure of the artery, and the expressions of Cat S,Mac,SMC,RECA,NFκB and iNOS was detected by immunohistochemistry technique.(3) 5 Wistar rats as normal control group and 11 rats which were randomly divided into two groups: diabetic group of 5 rats (GK group) and a-lipoic acid-treated diabetic group of 6 rats (ALA group,α-lipoic acid 35 mg/Kg-1 intraperitoneal injection qd alt). All the rats were fed with the high fat diet for 12 weeks. The expression of Cat S as well as subunits of NADPH oxidase p47 phox of aorta were detected using STBR Green RT-PCR. Ultrastructure of aorta was observed by electron microscope. Levels of MDA,SOD and GSH in serum were measured at the same time.Results: (1) There were no significant histomorphology changes of the aorta in STZ-induced diabetic rats for 4 weeks, but Cat S expression was obviously elevated in STZ-induced diabetic group.(2) There were no obvious morphologic changes between normal wistar rats and GK rats by light microscope in period of 12 week. The Cat S and macrophage-related antigen expressions in the aorta of GK rats were not observed. Absence in abnormal expression of SMC-related and endothelium-related antigens were shown. Expressions of NF-κB and iNOS in diabetic group were more obvious than those in the normal control group.(3) Compared with normal control group, the Cat S in mRNA content in GK group elevated , the differences were significant (P=0. 001). Cat S in mRNA content in LA group decreased compared with GK group, but the differences were no significance (P=0. 071). the p47phox in mRNA content elevated in GK group compared with normal control group (P=0. 862) , and decreased in LA group compared with GK group and normal control(P=0.164, P=0.155), but the differences were no significance. No obvious pathological changes of arteries in the three groups were observed by electron microscope. Compared with non-diabetic rats, there were significant increase in levels of serum MDA and decrease in levels of serum SOD and GSH in diabetic rats.α-lipoic acid normalized the levels of MDA,SOD and GSH.Conclusions: Short hyperglycemia causes abnormal expressions of several genes including the elevation of Cat S in the time of no morphological changes. In the condition of no obvious morphologic atherosclerosis formation in GK rats after feeding high-fat diet for 12 week, Cat S was detected to be elevated only in mRNA content to indicate that Cat S is not the initial factor of atherosclerosis, but the factor which can promote the development of these pathologic changes. In this period, NF-κB and iNOS are obviously expressed in the aorta.α-Lipoic acid may improve the total and local oxidative stress in T2DM, but it can not affect the expression of Cat S in mRNA content.
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