| In recent years, there is amount of evidence that coronary heart disease has become harmful to human health of a major non-communicable disease, its incidence and mortality rates gradually to increase, tending to be the first cause of death. At present, the modern medicine in the treatment of coronary heart disease has made great breakthrough, the main treatment have fibrinolytic therapy, coronary artery stent implantation, percutaneous transluminal coronary angioplasty, coronary artery bypass graft technology, etc. It is possible to make the mortality of coronary artery disease decline, but quite part of coronary heart disease patients do not apply the above treatment, making whole high fatality rate of coronary artery disease. Therefore, seeking effective and safe therapeutic targets for coronary heart disease has become a hot subject.Hydrogen sulfide is the third kind of endogenous gas signal molecules after the nitric oxide and carbon monoxide, which can lower blood pressure, inhibition of vascular smooth muscle growth and reduce vascular smooth muscle vascular remodeling effects. Early experimental data have shown that endogenous hydrogen sulfide could scavenge excess free radicals, reduce lipid peroxide gathered and calcium overload, and inhabit lipopolysaccgaride-induced nitric oxide production. At the same time the study confirmed myocardial ischemia as stress stimulation may induce endoplasmic reticulum stress and lead to endoplasmic reticulum stress chaperone glucose regulated protein78synthetic increases. But whether H2S had the effect on expression of GRP78in myocardial ischemia rats has not been reported. Therefore, we establish ISO-injured acute myocardial ischemia model in order to study the effect of degree of ischemic (duration) on the expression of GRP78. To observe the effect of H2S on the expression of GRP78on myocardial ischemia and preliminary discusses whether protective effects of H2S in the myocardial ischemia injury are mediated by altering the expression of GRP78in rats after giving H2S donors NaHS treatment.Forty-eight male SD rats were employed in present study. The experiment was randomly divided into five groups:control group, myocardial ischemia group (4h,8h,12h and24h). Myocardial ischemia was induced by subcutaneous injection of isoprinosine hydrochloride (10mg/kg) through multiple subcutaneous injection way. Saline (10mg/kg) was injected subcutaneously in control group. Another eighteen SD rats were randomly divided into three groups:control group, myocardial ischemia group and H2S administration group. NaHS (5.6μmol/kg), the donor of H2S was intraperitoneal injected after24h of ischemia. Saline (5.6μmol/kg) was intraperitoneal injected in control group and myocardial ischemia group. The electrocardiogram, myocardial enzyme spectrum indexes (aspartate transaminase, lactate dehydrogenase, creatine kinase, creatine kinase isoenzyme and alpha hydroxybutyrate dehydrogenase) and histological changes were detected to define the myocardial ischemia. The expression of GRP78mRNA in myocardium was detected by RT-PCR and Real Time-PCR.The experimental data was expressed with mean±standard deviation (x±S) Statistical comparisons were made using analysis of variance (ANOVA) and t test between different groups by SPSS program. Differences with P<0.05were considered statistically significant. Our results were shown as follow:1. Effect of the ischemia injury on the electrocardiogram, myocardial enzyme spectrum indexes and histological changes in the myocardial ischemia model of ratsCompared with the control group, rats in ischemia4h group displayed electrocardiographic ST segment depression; with the prolonged duration of ischemia, ST segment change is more obvious; the serum AST, CK, CK-MB, LDH and a-HBDH level increased significantly. HE staining showed that, some pathological changes in myocardium of normal rats, such as myocardial cells arranged closely, the nucleus is full, interstitial reactive hyperaemia oedema. Ischemia for4h rats myocardial began degeneration, osteoporosis, and myocardial cell hypertrophy; with the prolonged duration of ischemia, rat myocardial degeneration area significantly increased, and the emergence of sarcoplasmic solidification, gap widened, interstitial edema, with hemorrhage and lymphocyte infiltration.2. Effect of the ischemia injury on the expression of GRP78mRNA in the myocardial ischemia model of ratsThe GRP78mRNA were expressed in the control group and ischemia model of4h,8h,12h and24h rats; and compared with the control group, the expression of GRP78was significantly increased in myocardial ischemia for4h,8h,24h model of rats. 3. Effect of H2S on the electrocardiogram, myocardial enzyme spectrum indexes and histological changes in the myocardial ischemia model of ratsCompared with the myocardial ischemia24h group, rats in H2S administration group displayed electrocardiographic ST segment depression improved significantly; the serum AST, CK, CK-MB, LDH and a-HBDH level decreased significantly. Observed under the light microscope, myocardial cell of H2S treated group rats arrangement was neatly closely, lesions exhibited focal degeneration, solidification, ischemia pathological changes significantly improved.4. Effect of H2S on the expression of GRP78mRNA in the myocardial ischemia model of ratsCompared with the myocardial ischemia24h group, H2S significantly decreased the expression of GRP78mRNA in myocardial ischemia group.In conclusion, our results showed that the multi-point subcutaneous injection of large doses of ISO induced acute myocardial ischemia in rats, showing electrocardiographic ST segment depression, the serum AST, CK, CK-MB, LDH and α-HBDH level increased significantly. Myocardial cells occurred sarcoplasmic solidification, interstitial edema and other pathological changes; myocardial tissue GRP78expression increased. After exogenous H2S treatment, all the indexes of the myocardial ischemia were obviously improved and myocardial tissue GRP78expression decreased. This showed that exogenous H2S has a protective effect on rat acute myocardial ischemia injury induced by ISO, which may partly mediated by antagonism of endoplasmic reticulum stress and decrease of the expression of GRP78. |
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