The Effects Of Pioglitazone On Autoimmune Injuries To The Stomachs And The Derma In STZ-induced Diabetic Rats

Part-Ⅰ:The effects of pioglitazone on abnormal deposition of immunoglobulins on the stomachs and derma in STZ-induced diabetic ratsObjective:Diabetes mellitus (DM) is a metabolic disease characterized by chronic hyperglycemia. With the progress of the disease, there may be multiple systemic injuries which seriously affecting the quality of life of patients. The mechanism of DM is complicated and the etiology is not completely clear. At present the treatment of diabetes to control blood glucose, but can not completely block the course of the disease and the development of acute and chronic complications. Recently, many studies showed that immune and chronic inflammation play an important role in the initiation and development of diabetes and its complications. Pioglitazone is one of the thiazolidinediones drugs, which as ligands of PPAR-y ligands, be widely used in clinical patients as insulin sensitizers. Researches had found that pioglitazone has anti-inflammatory and immunumodulatory effects. So we try to investigate its effect on the deposition of immunoglobulins on the stomachs and derma in diabetic rats, explore the pathogenesis of diabetic gastroparesis and skin lesions, and provide a theoretical basis for clinical treatment.Methods:Ninety-six male SD rats were randomly selected twelve as the normal control group (H). The remaining rats were given streptozocin through the caudal vein to establish diabetic rats, then they were further randomized into seven groups to receive different agents, low dose pioglitazone group (A), big dose piolitazone group (B), low dose pioglitazone and insulin group(C), cyclosporine A group (D), cyclosporine A and insulin group (E), insulin group (F) and no treatment group (G). Sixteen weeks later, the rats were all sacrificed and the blood and urine samples were obtained to test serum albumin, liver and kidney function, blood lipids, urinary albumin. While the pathological change of stomachs and derma were observed by HE and TB (toluidine blue) staining technique and the disposition of immunoglobulins were detected by immunohistochemistry and immunofluorescence. The experimental results were analyzed by Image-Pro Plus 6.0 and the data were analyzed by SPSS 11.5.Results:The diabetic models were successfully established. The level of serum creatinine, serum urea nitrogen, and urinary protein were elevated in all diabetic rats. While the rats in pioglitazone treated groups had better results relatively and the liver function kept almost normal. The random blood glucose of all diabetic rats showed no decrease after treatment (P>0.05), while the fasting blood glucose level of C, E and F groups were lower than other groups (P<0.01). In diabetes rats, it can be found that gastric mucosal eosinophilia, increased gastric mucous cells, inner circular muscle layer in more muscle cell vacuoles. Meanwhile, the skin becomes thinner and hyperkeratosis, the follicular and hair are atrophy. The number of mast cells in mucosa and skin is increased performance. The disposition of IgG,IgA and IgM in the diabetes group was significantly increased compared with the normal group (P<0.01). In the drug treatment groups, the group with cyclosporine A combining insulin had the least immunoglobulin disposition (P<0.01), the group with big dose pioglitazone had similar result with the cyclosporine A group (P>0.05), and the low dose pioglitazone group had similar results as the insulin group.Conclusions:The stomachs and the derma are injured in diabetic rats, and immune abnormality took role in that injury. Pioglitazone may protect the stomach and derma from the injury as mentioned above through immunosuppressive action which was independent of the blood glucose and without liver and kidney injury.Part-Ⅱ:The effects of pioglitazone on the expression of MCP-1 and NF-κB on the stomachs and derma in STZ-induced diabetic rats Objective:The study above indicated that immune injury took part in the pathology of diabetes, since there is close relationship between immune reaction and inflammation. We detected the expression of MCP-1 and NF-κB in the stomachs and derma to further investigate whether piglitazone had the anti-inflammatory effect through the reduction of MCP-1 and NF-κB expression.Methods:The modeling and grouping of the rats were as same as the first part. The expression of MCP-1 and NF-κB was detected by immunohistochemistry, and the experimental results were analyzed by same method as before.Results:The expression of MCP-1 and NF-κB in the stomachs and derma of diabetic rats was significant than that in normal group (P<0.01), while in the diabetic rats, the no treatment group is the most (P<0.01), cyclosporine A combining insulin group showed the least expression (P>0.05), the big dose pioglitazone group had similar result with the cyclosporine A group, and the low dose pioglitazone group had similar results as the insulin group (P>0.05)Conclusions:The elevated expression of MCP-1 and NF-κB indicated the existence of inflammation injury in diabetic rats, both the stomachs and the derma were involved. The pioglitazone had anti-inflammation effect which may provide a new method for treating diabetes and its chronic complications.