ABSTRACT
Objective To establish a Juema minipig model of myocardial infarction, to evaluate the clinical indi?ces in the model pigs, and to explore the relationship between gene expression and metabolic decompensation. Methods 13 male Juema minipigs were randomly divided into control (Sham, n=5), myocardial infarction (MI, n=5) and normal control (for evaluating the recovery condition after surgery, n=3) groups. In the MI group, the ligation was done at the left descending coronary artery around the 1/3 distance to heart apex. Four weeks after the surgery, the cardiac function and serum biochemistry was analyzed. The histological changes and gene expression profiles in the myocardium in the peri?infarct area were exanimated. Results Ultrasonic images showed that the infarction was formed, the ejection fraction and fraction shortening were significantly reduced in the MI group ( ~32% and ~40% less than those of the sham group). Histological examination showed that myocardial fibers at the peri?infarct area were broken, dissolved, and there was con?nective tissue hyperplasia with increased neutrophil and lymphocyte infiltration. Microarray analysis revealed that two myo?cardial remodeling and pathology mediating pathways, three inflammation?related pathways, and 8 metabolic pathways ( in?cluding fatty acid, amino acid, and glucose metabolic pathways) were significantly changed. Conclusions We have suc?cessfully established a Juema minipig model of myocardial infarction. The less branches of the left descending coronary ar?tery allow us to establish a stable model by surgery with comparable characteristics in the clinic indices. The results of this study provides useful reference characteristics of an animal model with characteristic changes in the peri?infarct area.
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Objective Establishing the drug?resistant Candida albicans disseminative infected mice model for new drug screening. Methods The disseminative infected mouse model was generated by intravenously injecting a clinical Drug?resistant Candida albicans strain ( CaR) to immunosuppressive ICR mice. The features of model was evaluated by clinical symptom, survival condition, fungal burden in tissue, histopathology, cytokines assay and medication. Results After infected with CaR (0 day), the death of mice started at the first day, though, compared to clinical drug sensitive strain ( CaS) infected group, the difference of mortality rate in 16?day observation period was not significant in two groups (CaR, 90?7%;CaS, 86?2%, P =0?158), mice in CaR group died faster than those in CaS group at the early stage;On the fourth day of infection, Candida albicans could be detected in the different tissues, and we found fungal burden in kidney and brain was a significant difference. The typical granuloma caused by fungal infection was the main histopathological feature observed in the kidney, brain and heart. Cytokines in renal tissue were detected by flow cytometry, The changes of IL?1α,IL?6,TNF?αand IFN?γin kidney were significant. Compared with CaS group, IL?1 and IFN?γ were significantly higher and TNF?αdecreased significantly in CaR group. The mice of groups CaR and CaS were treated with 10 mg/kg fluconazole, the mortality rates were 83?3% and 37?5%, which have a significant difference. Conclusions In this study, we successfully established a drug?resistant Candida albicans disseminative infected mice model which is potential tool for the development of new anti?infectious agent.
ABSTRACT
To establish a stable mouse model of systemic Candida infection and to set up related standard operation procedure .Methods ICR mice were infected with C.albicans or C.parapsilosis by tail vein injection after immunosuppres-sion by cyclophosphamide .The quality control key points included immunosuppression , strain preparation, inoculation doses and the route of inoculation .Survival analysis , bacterial loads and pathological examination were performed to evaluate the prepared model .Results The developed model showed fugal-specific lesions in multiple organs , especially in the kidneys revealed by histopathological examination .Conclusions A stable mouse model of systemic Candida albicans infection can be successfully established by following standardized operation procedure .This mouse model may provide a useful tool for studies on pathogenesis and immune defense of fungal infection and new anti-fungal drug development and so on .
ABSTRACT
Objective To establish a guinea pig model for diagnostic reagent of tuberculosis.Methods By single or multiple subcutaneous injection of heat-killed H37 Rv in different doses in the groin of guinea pigs to establish a model of positive response to 0.1 mL (5 IU) standard tuberculin ( TB-PPD) skin test.Results Three doses of heat-killed H37 Rv ( 0.2 mg/mL, 0.3 mg/mL and 0.5 mg/mL ) could be used to generate the model of biological diagnosis of tuberculosis.After 24 and 48 hours, the diameter of red spot by TB-PPD skin test was 15.4 ±2.3 mm when a dose of 0.2 mg/mL heat-killed H37 Rv was administered for immunizing and allergizing the guinea pigs.The biggest red spot was induced at doses of 0.3 mg/mL and 0.5 mg/mL.The test results showed that the immune response induced by multiple njection to immunizing and allergizing guinea pigs was not significantly different than that induced by single immunizing injection, and the first skin test was better than the second, third and fourth skin test (P≤0.05).In addition, the body weight of the guinea pigs was still increasing after infection with heat-killed H37 Rv, and ulcers occurred in the injection sites in some guinea pigs.Conclusions A single subcutaneous injection of 0.2 mg/mL heat-killed H37 Rv in guinea pigs can be used well to establish a reliable model for biological diagnostic reagent of tuberculosis.Increasing the sensitizing dose and multiple sensitization can not increase the intensity of the delayed-type hypersensitivity ( DTH) response.