| Objective:This study aims to observe the effect of Des-Aspartate-angiotensin-Ⅰ(DAA-Ⅰ) on both TNF-a in the serum and NF-κB gene expression of myocardial tissue under myocardial injury state through subcutaneous injection with isoprenaline hydrochloride(ISO) to induce rodent model of myocardial ischemic injury in rat. Thus the protective action of DAA-Ⅰagainst myocardial ischemia would be evaluated with a view to provide experimental basis for further clinical research of drugs.Methods:1.Experiment animal group:rats were randomly selected and categorized into control group, model group, DAA-Ⅰprevention group, DAA-Ⅰtreatment group, DAA-Ⅰ+Danshensu group, Danshensu treatment group and valsartan treatment group.2.Animal model replication:As ISO possesses positive inotropic action and significant heart rate increasing effect on heart, ischemic myocardial tissue injury was induced by subcutaneous injection with ISO on Sprague-Dawley rats for twice continuously.3.From the 6th day onwards, control group and model group were injected with 0.9%NS i.p.; DAA-Ⅰtreatment group, DAA-Ⅰ+Danshensu group and Danshensu group were injected with DAA-Ⅰ(1013pmol/kg/d) and Danshensu(50mg/kg/d) respectively; valsartan group was treated with valsartan(30mg/kg/d) by gastric irrigation for a total of 7 days. DAA-Ⅰprevention group was injected with DAA-Ⅰ(1013/pmol/kg/d) continuously for 12 days.4.A11 the animals were subsequently administrated respectively with related medications and executed after 13 days of model building. Blood was collected from abdominal aorta to detect TNF-a content in the serum by ELISA assay, part of left ventricular myocardium was dissected for histopathological slices and NF-κB p65 gene expression of myocardial tissue was measured by RT-PCR method.Results:1.The serum TNF-a content of myocardial tissue of rats in the model group was 46.37±7.47 (ng/L) and was significantly higher than that in the control group(.P<0.01); compared with the model group, each treatment group was indicated an decrease in the serum concentration of TNF-αand NF-κB p65 gene expression of myocardial tissue at different levels(P<0.01/P<0.05); the gene expression level of NF-κB p65 in DAA-Ⅰ+Danshensu group was significantly lower than that of valsartan group(P<0.05). The TNF-αcontent was 34.80±7.764.82±3.55, 30.85±5.08,32.69±5.88,36.60±7.87 (ng/L).2.When compared with the model group, NF-kB p65 mRNA had a significant increase (0.568±0.085, P><0.01). Each treatment group NF-κB had different levels of increase. When compared with the model group, DAA-Ⅰtreatment group and valsartan group had meaningful difference(P<0.05). NF-κB/β-actin grey values were at 0.462±0.057 and 0.479±0.073. Comparison between treatment groups showed that DAA-Ⅰ+Danshensu had a gene expression level of 0.375±0.074 which was lower than the valsartan group.3.The cardiac muscle fiber structure of rats'left ventricular in the control group was distinct, regularly arranged, uniform nuclear staining, and cardiomyocytic gap was close without edema or fibrosis alteration; while myocardium of rats in the model group can be seen clearly hydropic degeneration, cell edema, dark stained nucleus with vascular bleeding, inflammatory cell infiltration, myocardial fiber atrophy, disordered arrangement and cardiomyocytic gap widened; compared with the model group, DAA-Ⅰprevention group, DAA-Ⅰtreatment group, DAA-Ⅰ+Danshensu group, valsartan group and Danshensu group all have ameliorated in various degree.Conclusions:1.DAA-Ⅰhas a significant inhibitory effect on the release of inflammatory cytokines such as NF-κB and TNF-a and the gene expression of nuclear factor-κB.2.Early intervention with DAA-Ⅰmay have a positive impact on myocardial ischemia and hypoxia, its beneficial effect in reversing the pathophysio logical process of RAAS may be as much as ARB class of drugs.3.Use a combination of DAA-Ⅰwith Danshensu has a more obvious protective action against myocardial ischemia; it's of a certain practical significance for improving therapeutic effects of ischemic heart disease as well as developing clinical strategy of integrated medicine in prevention and treatment of cardiovascular diseases.
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