Changes Of Cardiac And Renal Function In Rat Endotoxemia Associated Multiple Organ Dysfuntion Syndrome And The Significance Of Angiotonin Ⅱ Receptor In MODSE Caused By Infection

Infection is a main cause of multiple organ dysfunction syndrome (MODS), beginning with infection, then ALI, SIRS, ARDS, MODS, MOF, ending with destroying multiple organs thoroughly. Once above-mentioned symptom complex was initiated, we can't interrupt this process even if the etiopathogenisis and inducement were ablated. A series of inflammatory reaction and antiinflammatory reaction were generated when sepsis occurred, and a great quantity of cytokine and mediators of inflammation were released, meanwhile, the RAS was activated. So in order to interpret pathomechanism in sepsis and look for more protective device, it is important to study the change of RAS in sepsis. In this study, we aimed at researching the significance of angiotonin II receptor in MODSE caused by infection, the difference of angiotonin II receptor, including its characteristic and tendency along with the change of time in sepsis between young rats and elderly rats. We also tried to study the influence of angiotonin II receptor on apoptosis. According to this study, we try to find new evidence in basic research and clinical treatment in sepsis related to MODSE.Objective: We used LPS to make endotoxemia rat models, then we observed the changes of cardiac and renal function. At different time points, we examined the expression of receptor of AngII(AT1 and AT2), and at the same time we observed the changes of correlation factors related to apoptosis of Bcl-2 and Bax, the changes of contents of NO in tissues and serum. Thus we try to find the cause of changes of AT1R and AT2R, and a new way to protect and cure MOFE.Methods: In the first part of this study, we used LPS to make endotoxemia rat models. We observed the changes of cardiac and renal function byultraphonic and biochemical test, and pathological change by light microscope and electron microscope. In the second part of our study, we detected the expression of AT1 and AT2 receptor by immunohistochemistry, Western blotting and RT-PCR, and we detected the changes of NO in serum and tissues by the method of nitric acid reductase. Meanwhile, we detected the correlation factors related to apoptosis of Bcl-2 and Bax by immunohistochemistry, and changes of myocardial and renal cells apoptosis. In the third part of our study, we used anisodamine to interfere in endotoxemia, and then we detected the expression of AT1 and AT2 receptor by immunohistochemistry, Western blotting and RT-PCR, and we detected the changes of NO in serum and tissues by the method of nitric acid reductase.Results: In LPS-induced rat endotoxemia models, as time went on, the cardiac and renal function damage became more serious, it was significant in 6h(P<0.01), especially in elderly rats. And as time went on, the contents of NO in serum and tissues increased, it was significant in 6h(P<0.01); in the same time point(6h), the change in elderly rats group was sever than in young rats group(P<0.05), after interfered by anisodamine, the contents of NO decreased. And then, the expression of AT1 and AT2 receptor were decreased, especially in 6h(P<0.01); after interfered by anisodamine, their expression were up-regulation, but lower than control group. As the time went on, the expression of Bcl-2 was decreased, but the expression of Bax was elevated, and the ratio of Bcl-2/Bax raised in 2h in young rats group, and then diminished, but in elderly rats group, the ratio of Bcl-2/Bax had the downtrend.Conclusions: (1) In endotoxemia, the cardiac and renal function damaged in different degree, and more serious in elderly rats. (2) Interfered by LPS, the expression of AT1 and AT2 receptor descended, which was coincident to the degree of functional lesion, this result illustrated that may be down regulation of AT1 and AT2 receptor was related to functional lesion. (3) Interfered by LPS, the contents of NO increased, especially in elderly rats group, and had negativecorrelation to down regulation of AT1 and AT2 receptor, which indicated that overdose of NO may has correlation to down regulation of AT1 and AT2 receptor. (4) Interfered by LPS, apoptosis cells elevated along with the time, and elevated significantly in elderly rats group, apoptosis may correlate to overdose of NO and down regulation of AT1 and AT2 receptor. (5) In endotoxemia, Angll has significant role, the change of its main receptor may be the key point correlated to its degressive biological effect; therefore, to investigate the reason and find new protective path can help us find a new way to prevent and cure MOFE clinically.