The Experimental Study Of The Protective Effect Of Pentoxifylline On Myocardial Injury In Rats With Endotoxemia

The endotoxemia is a delicate problem to modern critical care medicine, and is also an important factor affecting the patient'prognosis. In the endotoxemia, the heart is one of the organs, which are liable to be affected. Once the heart complication appearing, the patient's condition will worsen suddenly and the mortality will increase. Because the endotoxemia's pathogenesis is complex, there are not enough effective methods to treat it. Therefore, seeking a effective method of treatment and strengthening the protection of patient's myocardium are more and more important. Pentoxifylline is a methylxanthine derivative, non-specific phosphodiesterase inhibitor and non-specific circumference blood vessel vasodilator. It can reduce the blood vessel resistance and improve the blood circulation of the brain and periphery. At the same time, it can improve the red blood cell distortion ability, reduce the fibrin density, suppress platelet gathering and improve the microcirculation. It is used in the diseases of periphery vessels. Now, more and more researches have discovered that PTX has the selective anti- inflammation function and may have the beneficial protective function to the tissue and cell in endotoxemia. In the research, we established the model of acute endotoxemia, took pentoxifylline as the research object and observed the changes of the expression of NF- kappa B, I- kappa B, ICAM-1 and HSP70 in myocardium and levels of TNF- alpha, IL-1 beta in serum. The aim is to discuss the mechanism of myocardial injury in rats with endotoxemia and PTX's function and mechanism in the myocardial injury in rats with endotoxemia, which can provide the basic theory for PTX's application.Part One Expression of NF-κB and I-κB in myocardial tissue in rats with endotoxemia and effects of pentoxifyllineObjective:To study the expression of NF-κB and I-κB in myocardial tissue in rats with endotoxemia and effects of penyoxifylline.Methods:Set the models of rats with acute endotoxemia by the method of injecting LPS directly. Wistar rats were randomly divided into 3 groups①sham operated control (S);②LPS (L);③PTX (P). In the LPS group, rats were given LPS (5mg/Kg) through the neck vein in 10 minutes, then were given the physiological saline comparison (total dose 5 ml/Kg). Method is the same as the PTX group. In the PTX group, rats were given LPS (5mg/Kg) through the neck vein in 10 minutes, then were given the PTX(10mg/Kg) through the neck vein in 10 minutes. After injection, PTX(10mg/Kg) were pumped into the rats by micro-pump in 50 minutes. The immunohistochemistry was used to assess the expression of the NF-κB and I-κB in the myocardial tissues. The Western blotting was used to assess the expression of the NF-κB in the myocardial tissues. The pathologic lesions of myocardial tissues were observed. Results:The levels of NF-κB and I-κB in the myocardial tissues in L group are higher than those in sham operated control group (P<0.01) (immunohistochemistry). The levels of NF-κB in the myocardial tissues in L group are also higher than those in sham operated control group (P<0.01) (Western blotting). After PTX treatment ,the levels of NF-κB in the myocardial tissues in P group are lower than those in L group (P<0.01) (immunohistochemistry, Western blotting), but the levels of I-κB in the myocardial tissues in P group are no different with those in L group (P>0.05) (immunohistochemistry). The pathologic lesions of myocardial tissues in P group are less serious than those in L group.Conclusion: NF-κB and I-κB take part in the progress of myocardial injury in rats with endotoxemia. PTX can eliminate the myocardial injury and protect the myocardial tissues by inhibiting the activation of NF-κB.Part Two Expression of TNF-αand IL-1βin serum and ICAM-1 in myocardial tissue in rats with endotoxemia and effects of pentoxifyllineObjective:To study the expression of TNF-αand IL-1βin serum and ICAM-1 in myocardial tissue in rats with endotoxemia and effects of penyoxifylline.Methods:Set the models of rats with acute endotoxemia by the method of injecting LPS directly. Wistar rats were randomly divided into 3 groups①sham operated control (S);②LPS (L);③PTX (P). In the LPS group, rats were given LPS (5mg/Kg) through the neck vein in 10 minutes, then were given the physiological saline comparison (total dose 5 ml/Kg). Method is the same as the PTX group. In the PTX group, rats were given LPS (5mg/Kg) through the neck vein in 10 minutes, then were given the PTX(10mg/Kg) through the neck vein in 10 minutes. After injection, PTX(10mg/Kg) were pumped into the rats by micro-pump in 50 minutes. The radioimmunoassay was used to assess the levels of TNF-αand IL-1βin serum. The immunohistochemistry was used to assess the expression of ICAM-1 in the myocardial tissues.Results:The levels of TNF-αand IL-1βin serum in L group are higher than those in sham operated control group (P<0.01) (radioimmunoassay). The levels of ICAM-1 in the myocardial tissues in L groups are higher than those in sham operated control group (P<0.01) (immunohistochemistry). After PTX treatment ,the levels of TNF-αand IL-1βin serum in P group are lower than those in L group (P<0.01) (radioimmunoassay), and the levels of ICAM-1 in the myocardial tissues in P group are also lower than those in L group (P<0.01) (immunohistochemistry).Conclusion: TNF-α, IL-1βand ICAM-1 take part in the progress of myocardial injury in rats with endotoxemia. PTX can eliminate the myocardial injury and protect the myocardial tissues by down regulating the levels of TNF-α, IL-1βand ICAM-1.Part Three Expression of heat shock protein 70 in myocardial tissue in rats with endotoxemia and effects of pentoxifyllineObjective:To study the expression of HSP70 in myocardial tissue in rats with endotoxemia and effects of pentoxifylline.Methods:Set the models of rats with acute endotoxemia by the method of injecting LPS directly. Wistar rats were randomly divided into 3 groups①sham operated control (S);②LPS (L);③PTX (P). In the LPS group, rats were given LPS (5mg/Kg) through the neck vein in 10 minutes, then were given the physiological saline comparison (total dose 5 ml/Kg). Method is the same as the PTX group. In the PTX group, rats were given LPS (5mg/Kg) through the neck vein in 10 minutes, then were given the PTX(10mg/Kg) through the neck vein in 10 minutes. After injection, PTX(10mg/Kg) were pumped into the rats by micro-pump in 50 minutes. The immunohistochemistry and western blotting were all used to assess the expression of HSP70 in the myocardial tissues.Results:The levels of HSP70 in the myocardial tissues in L group are higher than those in sham operated control group (P<0.01) (immunohistochemistry). The levels of HSP70 in the myocardial tissues in L group are also higher than those in sham operated control group (P<0.01) (Western blotting). After PTX treatment, the levels of HSP70 in the myocardial tissues in P group are higher than those in L group (P<0.01) (immunohistochemistry), and the levels of HSP70 in the myocardial tissues in P group are also higher than those in L group (P<0.01) (western blotting).Conclusion: The expression of HSP70 in myocardial tissues elevated in rats with endotoxemia. PTX can eliminate the myocardial injury and protect the myocardial tissues by further elevating the expression of ICAM-1.