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The Effects Of Pioglitazone On The Pathology And Immuno-inflammatory Index Of The Duodenum In STZ-induced Diabetes Rats

Posted on:2011-12-29Degree:MasterType:Thesis
Country:ChinaCandidate:J YuFull Text:PDF
GTID:2154360308968188Subject:Internal Medicine
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Objective:To investigate the effection of different dosege of the Piog on the function, pathology of the duodenum of the STZ-induced DM rats, as well as the the expression of the IL-10,TNF-aand the number and ratio of T cells on the same organs. And compare its effection with the immunomodulator cyclosporin A (CsA) and the insulin (INS). To find whether Piog has the effection to prevent and ameliorate the duodenum injury of the DM which through the immunizing mechanisms that mediated by the IL-10, TNF-aand ratio between CD4+ and CD8+ T lymphocytes. And provide the theoretical evidence for the usage of the Piog in the clinical practice.Materials and methods:Ninety-six healthy male SD rats were randomly divided into 7 DM groups and 1 healthy control group. According to the interventing mode, the DM groups were made by intravenous administration of STZ and then were divided into low dose Piog group, low dose Piog plus INS group, large dose Piog group, Cs A group, Cs A plus INS group, INS group, and DM group, respectively. The weight and blood glucose of each rat were investigated by routine test each month. After feeding 16 weeks, all rats were sacrificed. The serum was seperated and the urine was obtained to test the hepatic, renal function, triglyceride, insulin level and the urine albumin. The hematoxylin and eosin Stain, AB-PAS Stain were carried out to observe the goblet cells of the duodenum of the rats in different groups. On the same organs, the immunohistochemistry were carried out to detect the number of interstital cells of Cajal, CD4+ and CD8+T cells,deposition of the IL-10 antigen, and TNF-aantigen.Results:1. The STZ-induced DM rat model were successfully established; 2. Piog can significantly lower blood triglyceride and improving kidney function; 3. Congestion,edema and damage to the villus were found in the duodenum of DM group, Compared with the normal and DM control group,the duodenum of the large dose Piog interventing group rat and the CsA interventing DM groups are much better. 4. The number of goblet cells in the duodenum of DM group decreased,while compared with the DM group, Piog interventing group rat and the CsA interventing DM groups, The number of goblet cells in the duodenum increased to some extent.5. The number of Cajal cells in the duodenum of DM group decreased, while compared with the DM group,the Piog interventing group rat and the CsA interventing DM groups, The number of Cajal cells in the duodenum increased to some extent.6. The number of CD4+T cells in the duodenum of DM group increased, while The number of CD8+T cells decreased,the ratio between CD4+and CD8+T lymphocytes increased, compared with the DM group,the Piog interventing group rat and the CsA interventing DM groups, The number of CD4+T cells in the duodenum of DM group decreased, while The number of CD8+T cells increased,the ratio between CD4+ and CD8+ T lymphocytes decreased.7.Decreaed IL-10 and incresed TNF-a were found in DM group, while in the Piog interventing group rat and the CsA interventing DM groups, increaed IL-10 and decresed TNF-a were found.Conclusions:Apart from its insulin sensitization effect, Piog could also lower the blood triglyceride significantly and ameliorate the renal function of the DM rats. Diabetic rat duodenum changes in T lymphocyte subsets and inflammatory cytokines IL-10, TNF-a suggest abnormal expression of the immune system and inflammatory responses involved in the duodenum of pathological tissue damage, reduce of the number mucosal layer of goblet cells, muscularis of interstitial cells of Cajal, resulting in motor dysfunction of diabetic rat duodenum. The PIO, or CsA treatment can improve the duodenal mucosa T lymphocyte subsets and abnormal expression of cytokines, reduced organ inflammation, increased goblet cells and the number of interstitial cells of Cajal.Therefore, Piog is not only a medicine of INS sensitizer, but also is an immunomodulator for the preventing multi-organ immune damage of the DM.
Keywords/Search Tags:Pioglitazone, peroxisome proliferators activated receptorγ, cyclosporin A, Diabetes mellitus, duodenum, lymphocyte, cytokine, immunization
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