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Objective To study the differences of symptoms and pathological features of Wistar and Lewis rat models of collagen-induced rheumatoid arthritis. Methods Wistar and Lewis rats were injected with intermixture of bovine TypeⅡ collage and complete Freund's adjuvant(CFA)for first immunization, then strengthen it after 14 days and observed the incidence of Wistar-RA group and Lewis-RA group. The degree of paws swelling and the titer of serum anti CII antibody were determined. The pathological changes in toe and joint tissues were examined at 12 weeks, and the expressions of VEGF, IL-6, IL-10 and IL-17A in the synovial membrane of ankle joint were detected. Results After collagen induction,the Wistar and Lewis rats showed paw swelling after 10 d and 14 d,and peaked at 21 d and 24 d,the titer of serum anti CII antibody was significantly increased at third week(P< 0.01), and arthritis index(AI)was also significantly increased(P< 0.01). In the Wistar-RA rat group, the rate of molding was 80%, and at fifth weeks, the swelling of the paws subsided and went into a flat level. The molding rate of the Lewis-RA group was 100%,at the seventh week,the swelling of paws subsided and went into a flat level. At 12 weeks,the two model groups showed severe articular cartilage erosion, synovial hyperplasia and inflammatory cell infiltration, neovascularization and pannus formation in the joint synovium,and the bone mineral density of the femur and tibia of the hind limbs was significantly decreased(P<0.01). The expression of VEGF,IL-6 and IL-17A in synovium was significantly increased(P< 0.05,P< 0.01). The expression of IL-10 was obviously decreased(P< 0.01). Compared with the Wistar-RA group,the paw volume and paw thickness were increased for a longer time in the Lewis-RA group,AI was higher than that of the Wistar-RA group,synovial angiogenesis and pannus formation were more distinct, the expression of VEGF in synovium was significantly higher than that of Wistar-RA group(P< 0.05), while the expression of IL-17A was significantly lower than that in the Wistar-RA group(P< 0.05). Conclusions Both the Wistar-RA rat model and Lewis-RA rat model show joint swelling,deformation and decreased activity. AI is increased,the expression of VEGF,IL-6 and IL-17A increased,and the expression of IL-10 decreased,which are consistent with the clinical manifestation. The Wistar-RA rat model has a short duration of swelling, while the Lewis-RA rat model has a longer swelling duration and more severe joint damages. The neovascularization and pannus formation are more obvious. The expression of IL-17A in the Wistar-RA rat model is higher, while the Lewis-RA model has a highly expressed VEGF,which may be related to its pathological characteristics.
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AIM: To observe the expression of corticotropin releasing hormone (CRH) within the paraventricular nucleus of hypothalamus (PVN) and to explore the relationship between the activated CRH-containing neurons and sympathetic activity in rats with heart failure (HF).METHODS: Healthy male Sprague-Dawley (SD) rats were subjected to coronary artery ligation to induce HF, and chronic intracerebroventricular (ICV) infusion was performed by osmotic pump for 4 weeks.The rats in sham group and HF group were given vehicle (VEH;artificial cerebrospinal fluid 0.25 μL/h).The rats in HF plus treatment group were treated with CRH competitive inhibitor αh-CRH (15 mg/h).Meanwhile, the Lewis rats and Fischer 344 rats for control study also underwent coronary ligation to induce HF or sham surgery.After 4 weeks, left ventricular end-diastolic pressure (LVEDP) and maximum positive/negative change in pressure over time (±dp/dtmax) were determined.The right ventricular-to-body weight (RV/BW) and lung-to-body weight (lung/BW) ratios were calculated.The renal sympathetic nerve activity (RSNA) was recorded and the plasma norepinephrine (NE) level was measured.The expression of CRH in the PVN combined with the plasma adrenocorticotrophic hormone (ACTH) levels were measured.RESULTS: Compared with the sham-SD rats, the HF-SD rats had a greater number of CRH positive neurons in the PVN (accordingly the plasma ACTH levels were increased), accompanied by decreased ±dp/dtmax and increased RSNA, plasma NE, LVEDP, lung/BW and RV/BW.However, ICV treatment with αh-CRH attenuated these changes in the HF-SD rats (P<0.05).Compared with the sham-Fisher 344 rats, the HF-Fisher 344 rats also had a greater number of CRH positive neurons in the PVN (accordingly the plasma ACTH levels were increased).In addition, they had significantly increased RSNA and plasma NE level, higher LVEDP, RV/BW and lung/BW, and lower ±dp/dtmax (P<0.05).Compared with the SHAM-Lewis rats, the HF-Lewis rats had not significantly changed in the above parameters.CONCLUSION: In CHF, the CRH-containing neurons in PVN are activated, thus aggravating cardiac function by increasing sympathoexcitation.
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<p><b>OBJECTIVE</b>To study the influence of Yanyankang powder on Th1/Th2 in rats with experimental autoimmune uveitis (EAU).</p><p><b>METHODS</b>The EAU models were induced in Lewis rats by immunization with interphotoreceptor retinoid binding protein (IRBP) 1177-1191 in complete Freund's adjuvant. The rats were randomly divided into 3 groups: a model control group, a Yanyankang group, and a prednisone group, 9 rats in each group. The model control group was intervened with saline solution by gavage. The Yanyankang group was intervened with Yanyankang powder 4 g/(kg day) by gavage. The prednisone group were intervened with prednisone acetate tablets 5 mg/(kg d) by gavage. All groups were intervened after immunization once every 2 days for 18 days and monitored by slit-lamp biomicroscopy daily until day 18. The levels of gamma interferon (INF-γ) and interleukin-10 (IL-10) in the supernatants of T cells were determined by enzyme-linked immunosorbent assay. Polymerase chain reaction (PCR) technology was used for measuring Th1 and Th2 related cytokine mRNA expressions.</p><p><b>RESULTS</b>Slighter intraocular inflammation was found in the Yanyankang group and the prednisone group than the control group. The levels of the IFN-γ and IL-10 in the supernatants of the spleen lymph node cells were 382.33±6.30, 155.87±4.46 μg/L in the Yanyankang group and 270.93±7.76, 265.32±11.88 μg/L in the prednisone group. Both had significant differences compared with the control group (941.53±8.59, 20.67±4.65 μg/L; =0.01). The PCR results showed the same tendency.</p><p><b>CONCLUSION</b>Yanyankang powder showed favorable effects in the rats with EAU by influencing the function of Th1 and Th2 cells.</p>
Subject(s)
Animals , Female , Drugs, Chinese Herbal , Pharmacology , Therapeutic Uses , Eye , Pathology , Immunization , Inflammation , Pathology , Interferon-gamma , Genetics , Metabolism , Interleukin-10 , Genetics , Metabolism , Lymph Nodes , Metabolism , Powders , RNA, Messenger , Genetics , Metabolism , Rats, Inbred Lew , Spleen , Metabolism , Th1 Cells , Allergy and Immunology , Th2 Cells , Allergy and Immunology , Uveitis , Drug Therapy , Genetics , Allergy and ImmunologyABSTRACT
ObjectiveToinvestigatethekidneyyangdeficiencyconstitutionandhypothalamus-pituitary-adrenal ( HPA) axis dysfunction in Lewis rats .Method Two kidney yang deficiency models were established by subcutaneous injection of hydrocortisone and by adrenalectomy to induce hypothalamic -pituitary-adrenal ( HPA) axis dysfunction in Lewis rats.Wistar rats were used as control and compared with the two types of Lewis rat models of kidney yang deficiency .The degree of kidney yang deficiency of the Lewis rats was evaluated by examination and detection of the general signs , behavior , and neuroendocrine function , and so on .Result Compared with the normal Wistar rats , the body weight of Lewis rats was significantly higher than that of Wistar rats at the same age .The body temperature , urine volume and grip strength were significantly lower than those of Wistar rats ( P<0.01 for all ) .The memory ability of the Lewis rats was slightly decreased.The liver, kidney and adrenal indexes were significantly decreased in the Lewis rats (P<0.01).The levels of serum ACTH, CRH, cGMP, Cort and urine 17OHCS were significantly decreased (P<0.01).Conclusion A very slight deficiency of adrenal cortex function of Lewis rats is caused by genetic inheritance , and Lewis rats have the constitution of congenital kidney yang deficiency ( criticality or prophase of kidney yang deficiency ) .
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Objective To make comparisons of the three models of acute and chronic rheumatic carditis to find out an optimal animal model.Methods AntigenⅠwas a emulsifier mixed by complete freund’ s adjuvant( CFA) and Group A streptococcus(GAS).AntigenⅡwas mixed by incomplete freund’s adjuvant(IFA) and GAS.Female Lewis rats were randomly divided into four groups: A, B, C treatmeat groups were immuned with antigenⅠat the foot pad firstly. Subsequently, rats in group A、B、C were injected antigenⅠ, antigenⅡand activated GAS respectively to make the models of RHD.Rats in control group D were immunized with the same protocol outlined as treatment groups but without GAS. Respectively 7, 12, 24 weeks the rats were sacrificed 24 ( each group was 6).The blood biochemical item and Hematoxylin-eosin( HE) staining of hearts were detected.Results In group C the mortality was 25%.In group A, the incidence of carditis was the highest.Histopathological manifestations of group A, C was not only revealed acute damage such as inflammatory cell infiltrate as well as group B, but also the Aschofflike cells in the myocardial cells interstitial.But in group A and C there had a great degree of the inflammatory cells infiltration than group B.At 24th week rats in group A detected the rate and degree of valve fibrosis in chronic damage were higher than group B and C.None of rats in group D presented carditis or valvulitis.Conclusion In group A, giving the GAS with continuous stimulation after using the mixed emulsification of CFA and GAS to immune Lewis rats for five times was a appropriate method which could provide an optimal animal model for experimental study of acute and chronic rheumatic heart disease.
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Objective:To explore whether different phospholipid peptides could induce different pathological features of EAE in Lewis rats.Methods:Lewis rats were immunized with myelin basic protein 82-99 (MBP82-99),MBP68-86,and myelin oligodendroglia glycoprotein 35-55 (MOG35-55),respectively,and evaluated everyday for neurological scores.The cerebrum,brain stem,cerebellum and spinal cord of every rat were removed and pathological features observed.Results: Rats immunized with the two MBP peptides exhibited neurological signs of EAE wherein the central nervous system had extensive inflammation infiltration.The number of infiltrates in spinal cords in the two MBP peptides groups was higher than that in the cerebrums,brain stems and cerebellums.In spinal cords, there was no statistical difference of infiltrates between MBP82-99 and MBP68-86 groups;however,the both groups had more infiltrates than MOG35-55 group.Inflammatory cells were observed only in spinal cords of animals immunized with MOG35-55.Conclusion:This study provides certain evidence for understanding the diversity of pathological manifestations of EAE in Lewis rats.
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Aims: Collagen induced arthritis in rats is an important model for human rheumatoid arthritis. This study was designed to improve and refine this model by use of infrared thermography by measuring surface temperature of hind feet. Our hypothesis is that the local temperature on the feet correlates with other clinical parameters such as clinical score and edema and may serve as a method for quantification of the degree of inflammation. Study design: Experimental animal study. Place and Duration of Study: Institute of Biomedicine, University of Aarhus, Denmark between February and March 2010. Methodology: Arthritis was induced with collagen immunization in sixteen Lewis rats. Four of the animals were treated with dexamethasone to function as negative controls. Clinical scores were based on the magnitude of paw edema. The mean temperature of the hind feet (region covering the metatarsus and tarsus) was normalized with a reference area on the back of the same rat. The temperature index were compared with the clinical score index, edema index, and bodyweight of the rats Results: The mean hind feet temperatures increased with increasing clinical severity in the acute stage of the disease. There were positive correlation between temperature and clinical scores. Conclusion: The thermographic response appeared prior to the clinical signs, suggesting that thermography may be used as a predictive sign for the development of disease. This technique could be a non-invasive, objective, rapid, and reproducible method for evaluation of the degree of inflammation and effect of therapeutic interventions.
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Objective The pathological changes on SARS CoV infected Microtus brandtii,Lewis rat and Rhesus macaque and the possibility as SARS animal model were studied.Methods The amimals were infected with SARS-CoV through nasal cavity and sacrificed for collecting pathologic tissues after inoculation.The pathological changes,immuno-response and the replication of SARS-CoV in vivo were tested with microscopy,ELISA and virus isolation.Results Similar pathological changes were observed in SARS CoV infected Rhesus macaques,Lewis rats and Microtus brandtii and the pathological changes were similar with those of human.Conclusion All of the tree species of animals infected with SARS-CoV showned similar pathological changes with human SARS case.Among them,SARS-CoV infected Rhesus macaques is the best one in terms of pathological changes.Therefor the infected Rhesus macaque may be one of the most ideal animal model to study the pathogenesis and evaluation of anti-SARS-CoV vaccine.
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In order to test whether suppressor T cells are the responsible cell com-ponent in the induced resistance of Lewis rat against reinduction of Exp-erimental Autoimmune Encephalomyelitis(EAE)or not,attempts have beenmade to enrich a T cell population,which were functionally antagonistic tothe encephalitogenic activity of the EAE-inducing autoaggressive T cells,Lewis rats were passively induced for acute EaE by intravenous injectionof encephalitogenic,Myelin Basic Protein(MBP)-specific T line cell(S1cell). Nylon-wool-enriched spleen T cells recovered from animals passivelyinduced EAE,were cultured in vitro with irradiated encephalitogenic Tcells(S1)in the absence of antigen.The selective growth of T cell popula-tion with the phenotype of CD8 were found in the cultures.Functional ch-aracteristics of this cell population were studied both in vivo and in vitro.Thus,the S1-stimulated cells(Anti-S1 cells)are able to suppress both theantigen-and Con A-induced T cell proliferation of the antigenspecificT cell series.Studies on the in vivo activities of the Anti-Si cells couldhave shown that,pretreatment or posttreatment of the normal Lewis reci-pients with isolated Anti-Si cells are able to abolish or prevent thedisease-inducing activity of autoaggressive T cells.