| ObjectiveThe system of insulin-like growth factors includes insulin, insulin-like growth factor Ⅰ (IGF-Ⅰ) and insulin-like growth factor Ⅱ (IGF-Ⅱ) with multiple functions of regulatory factor on cellular proliferation.Their biological effect like insulin, and can promote tissue growth and development. They have dual-directional regulation effects. Based on different biological pathways, they can promote cell proliferation and differentiation, or inhibit cell apoptosis. IGF-Ⅱ among them can inhibit cell apoptosis with combining IGF-Ⅰ R, and protect myocardial cells after myocardial reperfusion.During heart transplantation, cell apoptosis in heart storage lighten operation effect. A focus of present research is to improve cardioplegic solution for reducing myocardial apoptosis and enhancing myocardium protection.To observe the myocardial protection effect of rat by adding insulin-like growth factor Ⅱ into St.Thomas’Ⅱ with langendorff and Neely isolated rat heart perfusion models in this study. MethodsSixteen SD rats were randomly divided into two groups:Control group (n=8), these isolated rat hearts were preserved in STH solution with4℃; Experimental group (n=8), these isolated rat hearts were preserved in STH+rh-IGF-Ⅱ (10ng/ml) solution with4℃. The heart was resected quickly from the thoracic cavity after anesthesia, connected soon to Langendorff’s heart perfusion system, perfused into aorta root of the heart with KHB in37℃, pH7.4,95%O2and5%CO2, The tube with pressure sensor was pass through the left atrial appendage, left atrium, left atrioventricular valve into the left ventricle chamber. The sensor was connected with M6240B multiple lanes of physiological signal acquisition and processing system to measure ventricular hemodynamic changes. After10minutes, the aortic perfusion was closed, left atrial infusion tube was opened into Neely left heart to do work, the coronary effluent fluid was collected for5minutes. The control group and the experimental group were treated with STH cardioplegic solution and rh-IGF-II+STH cardioplegic solution respectively. After cardiac arrest, these heart were put into STH solution and rh-IGF-Ⅱ+STH solution for storage at4℃in3hours. Then, the hearts were put on the Langendorff perfusion apparatus for perfusion in same condition with preservation condition. The detection of hemodynamic parameters before and after preservation of the hearts, and the calculation of their recovery rate were done; The measurement of coronary effluent fluid recovery rate and their contents of myocardial enzyme troponin I (Cardiac Troponin I, cTnI) in the fluid done too; After3hours of the preservation, the fluorescence assay was used to detect Caspase-3activity of the myocardial tissues in left ventricular anterior wall; The determination of myocardial apoptosis was got by TUNEL method.All the data were expressed as mean value±S.D, and analyzed by statistical software SPSS16.0. One-way analysis of variance was used between the groups. P-value<0.05was considered to be statistically significant. Results1.Experimental group showed higher recovery rate of LVSP, LVDP,±dp/dtmax and CF compared with the control group (p<0.05);2.The leakage of cTnI was lower in the experimental group (0.32±0.03ng/ml) compared with the control group (0.37±0.02ng/ml)(p<0.01).3.The level of caspase-3was significantly lower in the IGF-Ⅱ group(0.45±0.02activity unit) compared with the control group (0.52±0.04activity unit)(p<0.01).4. The apoptotic index in the experimental group (18.83±1.97%) was compared with the control group (22.35±2.90%), reduced the cardiomyocytes apoptosis (p<0.05).ConclusionIGF-Ⅱ added into St.Thomas’Ⅱ cardioplegic solution can incresase recovery rate of cardiac hemodynamic, coronary flow volume, and reduce the leakage of cTnI and the level of caspase-3, after fluid reperfusion of the preservated hearts. The apoptotic cells are reduced. It can improve cardiac function by reducing apoptosis and other damage. Thus, the addition of IGF-Ⅱ in the storage solution may be a promising strategy for donor heart preservation. |
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