The Relationship Between The Damage Of Myocardial And The TLR4/NF-kB Signal Pathway In The Sepsis Rat

Objective:At the present day, the widespread existence of sepsis does great harm to patient, as well as spending a large number of medical resources, whereas the current treatment of sepsis is lack of specific drugs and methods, thus the therapeutic options of sepsis need to be further expanded. Meanwhile the severe sepsis and septic shock are often followed by SIRS and MODs, by which the heart function is impaired primarily. Nowadays, prompt and adequate antibiotic therapy accompanied by surgical removal of infectious focus is the mainstay and also the only strictly causal line of therapy. In the present of septic cardiomyopathy, the therapy usually aims at improve the symptom whereas the effect is not compromising, and the specific medicine is not found. The mechanism of myocardial dysfunction which was followed by sepsis (sepic cardiomyopathy) has not entirely elucidate, but it was no disagreement that it's related to the over activated hosts'immune response and inflammation cascade. There were lots of studies about the local myocardial and syestemic inflammation pathway in sepsis patients, most of these over activated inflammation channels in host also have an essential and complex immune response which consisted the innate immune system. The current research conditions was still difficult to distinguish physiological from pathological roles played by each inflammation mediators accurately, thus the final happening was uncertain if we interfere with the mediators or inflammation pathway by drugs or other operation. Therefore, there were less weapon we can use in the clinical. The purpose of this study is to make clear the alternation of TLR4,NF-kB,TNF-αand NT-proBNP in the sepsis rats model which was induced by i.p. LPS. Then providing a basis evidence for the clinical theraphy of sepsis and cardiovascular dysfunction which was followed by sepsis.Methods:1.Animal model and experimental groups:healthy and clean SD rats 30, male, body weight 300-350g were randomly divided into 3 groups:control group 10:saline 5ml/only; LPS24h group 10:LPS 1Omg/Kg (in normal saline diluted to 5ml), intraperitoneally; LPS72h group 10:LPS 10mg/Kg (in normal saline diluted to 5ml), intraperitoneally; we sacrificed 24h,72h after the animals injected and the rats in control group at the same time points..2. Intubate a catheter through the right carotid artery to the left ventricle at 24 and 72h after intraperitoneal injection. RM6240 BD multifunctional physiological recorders,was used to record the average blood pressure(MAP),left ventricular end systolic pressure,pressure rise and fall of left the maximum rate of change (±dp/dtmax) and other cardcial function.3 Apical tissues were fixed, dehydrated, embeded, HE stained, and we oberseved the changes of cardiac pathology.4 RT-PCR was used to detect myocardial TLR-4 mRNA expression,and Western-blotting was used to detect the expression of TLR-4, NF-κB P65 protein.5 ELISA was used to measure the content of myocardial TNF-α,serum NT-proBNP.Results:1.Toxemia performance in rats:24h after injection of LPS, rats appeared fatigue sleepiness, reduction in the consumption of water, shortness of breath,increasing of eyes and nose's bloody dischange, diarrhea and weight loss. Heart and lung congestion were observed anatomically. All signs mentioned above were decreased or dinimished in the group of LPS72h.2.Compared with controlled group, LVESP,+dp/dtmax,-dp/dtmax decreased 24h after LPS injection (p<0.05), and rebounded till 72h.3.Pathology:The myocardical cell edema, degeneration and necrosis obviously after LPS injection 24h, till 72h the myocardical cell'damage was decreased.4.LPS24h group:myocardial TLR4 mRNA and TLR4, NF-κB 65 protein expression increased (p<0.05); all of those has no significant difference compared with control group in LPS72h group.5.In LPS24h group, myocardial TNF-α, serum NT-proBNP concen-tration increased significantly (p<0.05),and myocardial TNF-αwas rebounded to normal after LPS injection 72h but NT-proBNP not.Conclusion:1. The rat sepsis model could be established by intraperitoneal injection LPS(10mg/Kg), and the myocardial cells and function were obviously impairment.2. The TLR4/NF-kB signal pathway which involved in the dagame of myocardial cell and function in sepsis rat was over activitied in the rat sepsis model.