The Protectivie Effects Of N-n-Butyl Haloperidol Iodide On Sarcoplasmic Reticulum Ca~ (2+) -ATPase Of Rat Cardiac Myocytes During Ischemia-Reperfusion

As is well known, calcium overload is a major factor which contributes to the ischemia reperfusion. The quantity of SERCA is the biggest in cardiocytes, and its major responsibility is to pump Ca²⁺ back into the SR during relaxation and it plays a crucial role in regulating Ca²⁺ of cardiac myocytes. The activity of SERCA decreased will reduce the speed and quantity of SR reuptake Ca²⁺, and influence the quantity of Ca²⁺ in SR, in addition, it will have effect on the activity of ryanodine receptors （RyRs） and make the excitation-contraction （ECC） function decline. Previous research show that N-n-Butyl haloperidol iodide （F₂） could inhibit L-type calcium channel of cardiocytes and smooth muscle cells to prevent calcium overloading and had obvious protective effect in ischemia reperfusion injury and hypoxic/ischemic. However, there is no research if F₂ plays a protective effect in regulating calcium in cardiocytes. So the purpose of this study is to research the protective effect of F₂ on SERCA during I/R in rat myocardial tissue after ischemia reperfusion （in vivo）. The activity and quantity of SERCA were tested and to reveal the mechanism of the positive role of F₂ during I/R.Methods1. Established ischemia reprefusion model: according to the purpose of the experiment , there were different groups: ischemia for 30 min, reperfusion for 0min, 30min, 60min（this experiment is not over）and 120min, ischemia for 60min, reperfusion for 30min. The rat experimental models in vivo （I/R） were established by occluding left anterior descending coronary artery （LAD）.2. GroupsAll rats were randomly assigned into seven groups: Sham, I/R, and intravenous F₂, 0.25mg/kg, 0.5mg/kg, 1mg/kg, 2mg/kg and 4 mg/kg, before induction of ischemia. The ischemia of apex of left ventricular was detected.3. The expression of protein level of SERCA in myocardium was observed by western-blot. SERCA could decompose ATP into ADP and phosphorus （P） and and the activity of SERCA was detected by the tested kits through observing the quantity of P. Results1.F₂ preserved the reduction in normalized activity of SERCA during ischemia reperfusion As compared with sham treatment, the activity of SERCA was reduced during ischemia reperfusion, Intravenous F₂ at 0.25mg/kg, 0.5mg/kg, 1mg/kg, 2mg/kg and 4 mg/kg, could ameliorate the decreased activity of SERCA.2. Effect of F₂ on the protein level of SERCA during ischemia reperfusionThe protein level of SERCA did not change during ischemia for 30min and reprefusion for 0min, 30min, 120min as compared with the Sham. There was also no change during ischemia for 60min and reprefusion for 30min.Conclusions1. Ischemia and reprefusion could induce the activity of SERCA to decrease worse and worse, but the protein level of SERCA did not change.2. Intravenous F₂ in rats could ameliorate the decreased activity of SERCA dose-dependently during ischemia reperfusion, and probably this was another mechanism of F₂ playing the protective role in I/R.