| Reasear purposeHeart failure (HF) is predicted to be the21st century global problem of cardiovasculardisease. its incidence is high, the five-year survival rate was similar to malignant tumors.In recent years, many research showed there are many signaling pathways in cardiachypertrophy and heart failure play an important role in the process, especially theJAK-STAT pathway in cardiac disease. Many cytokines and immune biochemistryneurotransmitters can activate the JAK-STAT signaling pathway, which the start of thecorresponding gene transcription directly activate cardiac hypertrophy (compensatory) andcell survival related genes.The experiment research the role of IL-17in the process of heart failure throughJAK-STAT pathway. Explore whether IL-17can be caused cardiac hypertrophy, cardiacremodeling, and the role in the process of heart failure by participating in the JAK-STAT.The IL-17antibody affect cardiac remodeling by interferes with JAK-STAT signaltransduction,and thus delays the occurrence of heart failure and development.Adriamycin-induced change the level of p-JAK2/t-JAK in heart failure’s mouse bymyocardial tissue. From the point of view of animal experiments to research the signaltransduction mechanism of heart failure,Understanding the pathogenesis developmentprocess by heart failure,what is open up new theoretical perspective for the treatment ofheart failure, provide a new theoretical basis.Research methodsExperimental animal: healthy mouse’s wistar x24, weight is（200±20）g.A randomized divided into four groups,A: Anti-IL-17with heart failure group（n=6）； B：IgG with heart failure group（n=6）；C: Compare with heart failure group (n=6); D:Blank group (n=6).Adriamycin(ADR)-induced heart failure of model group with A,B,C.Preparation Methods: ADR with saline solution prepare2mg/ml solution byintraperitoneal injection of8times. The2and4day are ADR1mg/kg.ip. The6and8dayare ADR2mg/kg.ip. The10and12day are ADR31mg/kg.ip. The14and16day are ADR4mg/kg.ip.(Injected twice to increase1mg/kg). the contral group D: same time to use samevolume of saline solution.Innervations: Group A: Intraperitoneal injection of anti IL-17(100μg/0.8mlPBS,add0.2ml of air to make sure all anti IL-17spread to the entire abdominal); Group B;Intraperitoneal injection of IgG (100μg/0.8mlPBS); Group C,D: Intraperitoneal injection of0.8ml PBS. This experiment operate8times to do, injected at each (0.1ml/s), after injectionof0.2ml air to make sure all antibodies spread to the entire abdominal.Diagnostic indicators: Daily observation of the behavioral signs, and weightmeasurements.24h after the last injection, using Echocardiography monitors mouse aboutIVST, IVPWT, EF. Record data for comparison.After Echocardiography, observation of the morphological changes of the heart, lung,liver and kidney before weight and anesthesia of mouse. Remove the heart, to calculate theheart weight index, produced some of the myocardial tissue biopsy. Part of the myocardialtissue quick frozen in liquid nitrogen stored at-80℃. Western blot can be determinationp-JAK2/t-JAK2expression, the relative level of the RT-PCR detection of atrial natriureticpeptide (ANP).The statistical results: the use of statistical software SPSS13.0analysis.Results:A, B, and C are different degrees of heart failure phenomenon, Group D is normalgrowth. Four groups of terminal body weight is increased, Group D is increasedsignificantly (P<0.05).Observation of Echocardiography, IVST: group A,B,C was thicker than that in groupsD (P<0.5). LVPWT: group C was fatter than that in group anti-A, B, D. EF: group A,B,Cwas decreased than that in group D (P<0.5). Heart Quality: A,B,C group compared with group D had no significant statisticaldifference (P>0.05).The heart weight index: Group A,B,C was bigger than in group D (P <0.05), group Awas smaller than the group C (P <0.05); between B and C was no significant difference (P>0.05).Myocardial pathological changes: Group A,B and C are different degrees ofmyocardial damage, group D is normal.Myocardial tissue samples (p-JAK2/t-JAK2) for Western blot analysis:p-JAK2/t-JAK2has a little bit of display. Group A,B,C was increased than group D. CGroup was decreased to compare with group A,B.Group A,B,C compared with group D had no statistically significant difference (P>0.05), but group B, C was bigger than group A,D.Conclusion:The above data show that the JAK-STAT signaling pathway is activated to expresst-JAK2, and part of rapid activated to generate p-JAK2。These results also show thatanti-IL-17antibody can induced the JAK-STAT signaling pathway activation, makep-JAK2/t-JAK have increased expression, with echocardiography testing results show that,JAK2has a certain degree of myocardial protection. |
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