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Effect of CP-690550 on the Acute Rejection of Allogeneic Heart Transplantion in Mice

Author: MingFei
Tutor: XiangDaoKang
School: Zunyi Medical College,
Course: Cardiothoracic Surgery
Keywords: Heart transplant Rejection CP-690550 CsA STAT3 IL-12 Mice
CLC: R654.2
Type: Master's thesis
Year: 2009
Downloads: 12
Quote: 0
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Abstract


Objective: To study the mice after heart transplantation using specific Janus kinase 3 (Janus Kinase 3 JAK3) inhibitors - CP-690550 the transplanted heart signal transduction and transcription activation factor 3 (signal transducerand activator of transcription 3 STAT3) and cell the content factor IL-12 ( interleukin-12 ) ; the observed cardiac allograft survival time and changes in cardiac pathology , and to explore the mechanism of action of the mouse heart transplantation after acute rejection . Methods: cervical heterotopic heart transplantation model of allogeneic mice , were randomly divided into intervention group , the CsA ( ring cyclosporin A ) and control groups , and each group n = 6 . The intervention group and CsA mice the day of surgery and postoperative were treated with CP-690550 and CsA oral ( both 10mg.kg -1 d -1 < / sup >) to the transplanted heart arrest , the control group did not give oral medication record three groups of cardiac allograft survival time . Take the transplanted heart specimens were detected by immunoblotting (western blotting) specimen surface STAT3 ; enzyme-linked immunosorbent assay (ELISA) was detected specimens surface IL -12 ; Paraffin sections, HE staining was observed myocardial lymphocytic infiltration situation. Results: 1 . Intervention group cardiac allograft survival time (6.17 ± 0.75d) was significantly longer than the CsA group (4.67 ± 0.52d) and the control group ( 3.00 ± 0.63 d ) ( F = 36.62 , P <0.05 ) . 2 microscope transplanted heart (HE staining 200 times ) , myocardial lymphocytic infiltration of the CsA group and the control group than the intervention group seriously . 3 heart specimens in the intervention group phosphorylation of STAT3 content of the reference value (0.23 ± 0.05) was significantly less than the CsA group (0.29 ± 0.06) and control group ( 0.47 ± 0.07 ) ( F = 75.39 P <0.05 ) . The intervention group heart specimens IL -12 content (142.24 ± 34.10pg/ml) significantly less than the CsA group (202.34 ± 64.10pg/ml) and control group ( 282.03 ± 51.89pg/ml ) ( F = 5.30 P <0.05 ) . Conclusion : CP-690550 by reducing phosphorylation in cardiac allograft active STAT3 content , thereby inhibiting JAK3-STAT signaling pathway , inhibition of dendritic cell maturation and release of IL-12 -induced T cell anergy , causing immune tolerance anti- acute rejection , thus prolonging cardiac allograft survival time , and better than that of CsA .

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CLC: > Medicine, health > Surgery > Of surgery > Cardiovascular and lymphatic system surgery > Heart
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