The Protective Effects of Monophosphoryl Lipid A on the Ischemic Myocardium and Endothelium in Rats
|School||Central South University|
|Keywords||Monophosphoryl lipid A Low-density lipoprotein Endothelial dysfunction Inducible nitric oxide synthase Asymmetric dimethyl arginine|
Coronary heart disease is the result of coronary atherosclerosis. LDL oxidation can significantly damage the endothelium-dependent relaxation of vascular function, and vascular endothelial damage in atherosclerosis formation and development plays an important role. Studies have shown that high-fat diet-induced atherosclerosis in rabbits may exacerbate myocardial ischemia-reperfusion injury, this damage can be reversed by NO donor. Monophosphoryl lipid A (MLA, a non-toxic derivative of endotoxin) can significantly reduce the ischemic myocardium and vascular endothelial injury, this protective effect on the induction of iNOS generation. This paper gives a non-modified low-density lipoprotein (LDL) induced endothelial injury in a rat model of acute study MLA of LDL induced vascular endothelial injury and myocardial ischemia. Method: ① vascular injury model: 48 hours before the experiment, SD rats under ether anesthesia, sublingual vein injection of human serum LDL-induced endothelial dysfunction. Rats in 3% sodium pentobarbital anesthesia, carotid artery blood to detect blood-Africa ADMA (ADMA, high performance liquid chromatography) were measured and observed in vitro thoracic artery rings endothelium-dependent relaxation response. ② cardiac ischemia-reperfusion model: Langendorff perfused rat hearts. 30min 30min global ischemia caused by ischemia and reperfusion - reperfusion injury. Left ventricular balloon catheter, connected Macintosh 7220 computer, using PowerLab biological signal acquisition system to record, analyze heart rate, left ventricular pressure and left ventricular pressure change rate (± dp / d tmax . Timed collection of coronary effluent (CF) and determine which creatine kinase (CK) activity. Results: ① LDL significantly inhibited acetylcholine-induced vasodilatation, accompanied by serum ADMA (endogenous NOS inhibitor) concentration increased. MLA (300 , 450 Yi / kg, medium) can improve LDL induced a dose-dependent endothelial damage, decreased serum ADMA concentration H selected NOS inhibitors LNAME can cancel MLA vascular protection, and selective iNOS inhibitor aminoguanidine this without impact. ② LDL can aggravate ischemia caused by coronary flow commanded bundle wrapped in cloth Note the decrease, but a loss of heart function were exacerbated. MLA can significantly reduce these two factors caused damage to myocardial injury. CONCLUSION: ① single dose intravenous LDL can vascular endothelial-dependent vasodilation, increased due to coronary ischemia-reperfusion injury; ② MLA protective effect on the vascular endothelium and reduces blood clearance ADMA concentration; ③ MLA of LDL pretreatment of animals with cardiac ischemia-reperfusion injury protection made.