The Protective And Synergistic Effect Of IL-1ra-Fc-IL-18BP On Myocardial Ischemia Reperfusion Injury In Rats

Myocardial ischemia reperfusion injury （MIRI） refers to restore ischemic heart muscletissue perfusion, cause reperfusion area myocardial cell and local blood vessels nets have asignificant pathological changes of physiological, these changes common function can leadto further tissue damage.IL-1ra-Fc-IL-18BP is to IL-18binding proteins （IL-18BP） and IL-1ra connectedthrough the Fc period, the molecular completely different from IL-18BP and IL-1ra-Fc,, itreaches the same inflammatory site, as inflammatory factor blockers, can also block the twocell factors of signaling pathways, completely blocked IL-1receptor mediated familysickness. The fusion of molecular injection frequency decrease, side effects may be moresmall, and the effect is better. IL-1ra and IL-18BP-Fc integration, increased IL-18BP-Fc’smolecular weight, and increased two glycosyl the site, so that prolonged the half-life insideits body. IL-1ra in the human body is safe, but its curative effect is not enough to completelyblocked IL-1receptor mediated diseases. IL-18BP-Fc in early clinical study is safe, but italso may not be completely blocked IL-1receptor mediated diseases family. AndIL-1ra-Fc-IL-18BP can also blocking IL-18and IL-1, can completely blocked IL-1receptormediated phlogistic pathways. Early studies have demonstrated that this molecule isanti-inflammatory, now to investigate the myocardial ischemia and reperfusion injury themodel is a protective effect, and the clinical treatment of myocardial ischemia andreperfusion injury aspirin and nitroglycerin about whether there is a synergy.The rat coronary artery ligation of the left anterior descending30min reperfusion120min making myocardial ischemia and reperfusion injury as model, the method is as follows:after anesthetised with ether, rats were face upward fixed on the operating table. The chestwas opened between the left third and fourth rib and the heart was exposed. Find the leftanterior descending coronary artery and a nylon suture attached to a fine needle was placedunder the left anterior descending coronary artery and ligated coronary artery immediately.After the heart was return into the chest, the blood and water in the chest were squeezed outand close the chest swiftly. The time opening the chest is no more than30seconds. Shamsurgical group placed the suture only but not ligate coronary artery. Each animal in finishafter ligation operations were under the tongue to medicine or venous saline, then again exposed the heart, with surgery cut off the line on the blade ligation reperfusion.Experimental observation IL-1ra-Fc-IL-18BP to MIRI rats’ SOD, MDA, MIS, organizationmorphology, serum myocardial enzymes and Ca²⁺influence.Results:IL-1ra-Fc-IL-18BP25,50,100，200and400mg/kg group can decrease ratsmyocardial infarction range （MIS）, Aspirin+Nitroglycerin group and Aspirin+Nitroglyce-rin+IL-1ra-Fc-IL-18BP group all can decrease rats MIS, but no obvious difference betweenthem; IL-1ra-Fc-IL-18BP200,400mg/kg group could obviously decrease serum ASTactivity, IL-1ra-Fc-IL-18BP100,200,400mg/kg group could obviously decrease serum LDHactivity, IL-1ra-Fc-IL-18BP200,400mg/kg group and PGE1group could obviously decreaseserum CK activity, Aspirin+Nitroglycerin group, Aspirin+Nitroglycerin+IL-1ra-Fc-IL-18BPgroup could obviously decrease serum AST, CK, LDH activity, but no obvious differencebetween them; In addition, IL-1ra-Fc-IL-18BP50,100,200,400mg/kg group and PGE1group were significantly lower the MDA content rats, also can obviously improve the serumSOD activity, Aspirin+Nitroglycerin group and Aspirin+Nitroglycerin+IL-1ra-Fc-IL-18BPgroup were significantly lower serum MDA content, also can obviously improve the serumSOD activity, but no obvious difference between; IL-1ra-Fc-IL-18BP25,50,100,200,400mg/kg group and PGE1group to rat myocardial morphological structure damage will beimproved obviously effect, Aspirin+Nitroglycerin group and Aspirin+Nitroglycerin+IL-1ra-Fc-IL-18BP to rat myocardial morphological structure damage also has the obviousimprovement action, but there was no obvious difference.In short, IL-1ra-Fc-IL-18BP200,400mg/kg group can decrease myocardial ischemiaand reperfusion injury rat MIS, and against free radicals cause oxidative damage, and reducethree enzymes of myocardial. So200mg/kg is the best choice to do the nest test. In addition,IL-1ra-Fc-IL-18BP200mg/kg to Aspirin+Nitroglycerin no obvious synergy.