| As the increasing number of patients with chronic heart failure, attacksof acute decompensated heart failure and acute heart failure have beenbecoming the main cause of hospitalization in patients with heart failure,and almost two thirds of the patients are caused by ADHF. According tosurveys in our country , the infection is the common inducement of ADHF.While the senile patients'infection is mainly caused by G– bacillius, theLPS in their cell walls plays a key role. ADHF model was established byLPS on mice. To explore the pathology mechanisms of inflammatoryfactors and the rate variation of cell signaling pathway on ADHF model.Recent studies have demonstrated that erythropoietin not can reducesystemic infection disease caused by bacteria by NFκB pathway, but alsoplays significantly protective role to heart, brain and so on. This study is toinvestigate whether EPO has the protective effect on ADHF stage, andpreliminarily to analyse the molecular basis of its role.Therefore, this experiment was arrangaled into two steps. The firststep: The CHF model was established by intraperitoneal injection of thedoxorubicin, then the ADHF model was induced by LPS, in order toobserve the changes of systemic inflammatory and cell signaling pathway.Fifty male C57B1/6 mice were randomly divided into four groups asfollows: normol (Nor) group, Dox group, D&L group and LPS group. InDox group and D&L group: Each mice was injected intraperitoneally withDOX at a dose of 5 mg·kg-1 body weight once a week. When thecumulative total dose of DOX reached to 30 mg·kg-1, all CHF mice modelswere established. From the seventh week, the mice of LPS group and D&L group were injected intraperitoneally with LPS at a dose of 5 mg·kg-1 bodyweight to make ADHF model. After one week, the mice were examined byechocardiogram; the concentration of IL-6 in mice plasma were measuredby ELISA. The protein expressions of p-STAT3, Bcl-2, Bax in themyocardial biopsy were detected by soft ware immunohistochemicalanalysis, and we converted this image to quantitative data by imageProPlus 6.0 , and then did statistical analysis. The second step:ADHFmodel was established as described above, and then we injected EPO toinvestigate whether EPO had a protective effect on ADHF stage, andpreliminarily analysed the molecular basis of its role. Fifty male C57B1/6mice were randomly divided into four group as follows: normol (Nor)group(n=10); Dox group(n=10); D&L group(n=10); D&E group(n=10);ADHF model were builted. On the seventh week , the mice of D&L andDLE were injected with LPS, and the mice of D&E group and DLE groupwere injected with a single dose of EPO at a dose of 5000 iu·kg-1.Observed one week, from eighth week on, the mice were examined byechocardiogram; the concentration of IL-6 and brain natriuretic peptidewere determined in plasma. Heart weight index was measured. the proteinexpressions of p-STAT3,Bcl-2,Bax in the myocardial biopsy weredetected by immunohistochemical analysis,and we converted this image toquantitative data by soft ware image ProPlus 6.0 , and then finishedstatistical analysis.The following conclusin are obtained from the above processes.Thefirst step:compared to Nor group, the PWTd and LVESd in DOX groupmice were obviously higher, while LVEDd and FS was significantly lowerthan that. Compared with DOX group, the LVEDd and LVESd contents inD&L group were largely increased. However the PWTD and FS content inD&L group were decreased significantly. These data suggested mouse'sheart chamber was expanded, ventricular wall was thinner, the systolicfunction was damaged, while the mentioned Nor group and LPS group haven't statistical significance. There isn't statistical significance in thelevel of IL-6 of plasma in Dox group and LPS group , however it wassignificantly higher than that of Nor group(P<0.01); The levels of IL-6 ofplasma in D&L group were significantly higher than these of Dox group.Compared with Nor group, the expression of Bax, Bcl-2 and p-stat3 wereincreased, and those of Dox group were significantly increased(P<0.05),and positive rate of Bcl-2 were more significant than Bax; The expressionof Bax in D&L group were more significant than these in Doxgroup(P<0.05), while the expression of Bcl-2 and p-stat3 weredecreased(P<0.05). The results of the second step: Compared to D&Lgroup, the depth of ventricular wall were thinner, and the result of FS weresignificantly increased(P<0.05). There was no difference in statistics levelof IL-6 in plasma between DLE group and D&L group, but the plasmalevel of BNP in DLE group were significantly less than that in D&Lgroup(P<0.05); The expression of Bcl-2 and p-stat3 in DLE group wereobviously increased (P<0.05), while the expression of Bax weresignificantly decreased(P<0.05).The conclusin can be shown from the first part of the experiment:myocardial systolic and diastolic function of LV in mice with chronic heartfailure after injection of LPS are decreased, suggesting that the model ofADHF mice was established successfully. The level of IL-6 weresignificantly increased in plasma of ADHF mice. The levels of Bcl-2,p-STAT3 decrease and the expression level of Bax was twice more thanthat of Bcl-2 . Cardiomyocyte was induced from hypertrophy to apoptosis.Consequently, the balance between mice myocardium cells JAK-STATsignaling pathway and suppressor of cytokine signaling was disordered asheart failure by LPS, which accelerates the expression of proapoptotict andcontributing to myocardial cells'apoptosis. The conclusin of the secondpart suggested, The plasma levels of inflammatory cytokines were inhibitedafter the mice were injected with EPO, and myocardial cells tend to hypertrophy, cardiac systolic and diastolic function were significantlyimproved. ADHF mice ventricular wall thickness is increased, and theexpression levels of FS was significantly increased .There is no differencein statistics levels of IL-6 in plasma. The expression levels of Bcl-2 andp-stat3 were significantly increased, while the expression levels of Baxwere significantly decreased. Inferring, EPO significantly increases theexpression levels of p-STAT3 and establishes a new balance withsuppressor of cytokine signaling, so inhibits the cardiomyocyte apoptosisand has a good protective effect on ADHF.
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