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Background Most animal models of experimental autoimmune uveitis (EAU) are single attacked procedure,with a different feature from the natural course of human recurrent autoimmune uveitis.So establishing a recurrent EAU model is necessary for the clinical study on EAU.Objective This study was to establish the recurrent EAU model in rat and investigate the ocular inflammation and pathological manifestation and interleukin-17 (IL-17)expression in the eye.Methods T cells isolated from the spleen and draining lymph nodes of Lewis rats immunized with interphotoreceptor retinoid-binding protein (IRBP) 1177-1191 peptide fragments (R16) 10 days earlier were re-stimulated with R16 in vitro and injected into naive syngeneic rats to establish the recurrent EAU models,and the normal Lewis rats were used as controls.The eyes of model rats were then examined daily for clinical signs of uveitis by slit-lamp biomicroscopy and scored Caspi's criteria.The rats were sacrificed 1 month,2,3months after injection respectively,and the retinal sections were prepared for the pathological examination by hemotoxylin & eosin staining.Immunohistochemistry was performed to detect the expression of IL-17 in the retina.Results Adoptive transfer of R16-specific T cells to Lewis rats induced recurrent uveitis.The inflammatory scores on the fourth day,the sixth day,and the inflammatory response disappeared on the tenth day after injection.However,the inflammatory reaction occurred repeatedly 4 or 5 times in the 2-month duration after that,and the right and left eyes of a single recipient showed a different pattern of relapse,and the clinical manifestations of EAU was similar to the natural course to those of human autoimmune uveitis.In the retinal specimens of 1-,2-and 3-month group,the number of inflammatory cells was gradually decreased as the time lapse.Compared with the normal group,the thicknesses of the entire retina,outer nuclear layer and inner nuclear layer decreased with a significant difference among the 4 groups (F=20.46,288.40,4.43,all P=0.00).The number of RGCs in the normal group,1-,2-and 3-month group was 231.27 ± 15.36,225.36 ± 17.79,132.18 ±9.39 and 67.45 ± 11.90,respectively,showing a significant difference among them (F=68.94,P=0.00).Immunohistochemistry showed that the scores of the IL-17 expression in the rat retina were 0.64 ± 0.17,1.92 ± 0.19,1.17 ± 0.23 and 0.83 ± 0.23,showing statistically significant difference (F=64.10,P=0.00).Conclusions The stimulation of R16-specific T cells can induce recurrent EAU in Lewis rat.Th17 is involved in the disease course.
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Objective To establish a animal model for diffusion mesangioproliferation complicating focal segmentally glomerulosclerosis.Methods The models were established in the seventieth day by repetitive injection of 4mg/kg and 3mg/kg adriamycin to the SD rats in the 7th and 30th day after removal of their right kidneys.Results Serious edema, profuse albuminuria, hypoalbuminemia, hyperlipemia and renal failure were presented. Simultaneously, diffuse medium- or serious-grade proliferation of mesangial matrix, slight-grade proliferation of mesangial cells, segmental sclerosis of 22% of glomeruli, and overexpression of PDGF-B and bFGF in glomeruli were showed by pathologic examination, computerized image analysis and immunohistochemistry staining.Conclusions The models established in the transition stage from mesangioproliferation to glomerulosclerosis are helpful to study mechanisms and take measures for prevention and cure of chronic glomerulonephritis.
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Objective To investigate the mechanism of renal interstitial fibrosis after unilateral ureteral obstruction and renal protctive effect of angiotensin coverting enzyme inhibitor (ACEI),benazepril on rat kidney.Methods Twenty-four rats were randomly assigned to shame operation group (normal group),operation group, benazepril(10mg?kg -1 ?d -1 ) treatment group after unilateral ureteral obstruction. Renal tissues were examined by light and electronmicroscopy at the 2nd week after operation. Immunohistochemistry was applied to measure the expression of collagen Ⅲ,transforming growth factor ? 1 (TGF-? 1 ) and nuclear factor-kB(NF-kB) in the renal interstitium.Results In comparison with shame operation group, the expression of collagen Ⅲ , TGF-? 1 and NF-kB in the interstitium of operation group markedly increased (P
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Objective To explore the molecular mechanism of glucocorticoid and high glucose-induced insulin resistance(IR).Methods Isolated rat adipocytes were cultured for 24h at 5 or 25 mM glucose with or without dexamethasone (Dex) 0 3?M. Then the glucose uptake , the phosphorylation of tyrosine of insulin receptor substrate (IRS)1/2 and expression of IRS 1/2 and protein kinase B(PKB) protein were measured by western blot analysis with molecular dynamics. Results These adipocytes treated with 25 mM glucose have shown to impair glucose uptake, IRS1 phosphorylation and the protein expression; Combined treatment with Dex enhanced high glucose-induced the suppression, and inhibited IRS1 tyrosine phosphorylation; High glucose increased IRS2 protein expression, Dex abolished partly its the effect. Conclusions High glucose can induce IR, Dex can aggravate the effect induced with high glucose. The mechanism may be involved in affecting the phosphorylation and expression of insulin signaling proteins.