| Objective:This study aims to observe both IL-1βin the serum and ICAM-1 gene expression of myocardial tissue on the rat model of myocardial ischemic injury induced by subcutaneous injection with isoprenaline, to evaluate the protective effect of Des-Aspartate-angiotensin-I (DAA-â… ) and Danshensu in experimental inflammatory response to myocardial ischemic injury and explores the two drugs share synergistic action.Method:1.Experimental groups:68 SD rats were divided into 7 randomized groups, which were normal controlled group, model self-healing group, DAA-I treatment group, DAA-I preventative treatment group, DAA-I and Danshensu treatment group, Danshensu treatment group and valsartan treatment group.2. Model replication:Rat models of ischemic myocardial injury was adopted by the means of two consecutive days of injecting isoprenaline subcutaneouly and first ISO dosage was 4mg/kg, secondary dosage was 2mg/kg.3. Drug intervention schemes:From the first day of ISO injection, the rats of the DAA-I prevention group were continuous administered DAA-I (1013pmol/kg/d) for a total of 12 days, while the rest groups were temporarily not treated. From the sixth day onwards, each group was began to give corresponding drug intervention:the normal controlled group and the model self-healing group were intraperitoneal injected with physiological saline; the valsartan group was irrigated the stomach with valsartan (30mg/kg/d); the rest treatment groups were dealed with DAA-I (1013pmol/kg/d) and Danshensu (50mg/kg/d) correspondingly by intraperitoneal injection. The above groups were treated for a total of 7 days.4. Index test:Each experimental group rats were treated accordingly with the refered drugs. On the 13th day after model replication, drawed some blood from abdominal aorta to test the content of IL-1βin the serum by the method of ELISA, and dissected part of the left ventricular myocardium to detect ICAM-1 gene expression of myocardial tissue by the way of RT-PCR, and took the rest part for myocardial histopathological slices in order to observe the myocardial tissue pathomorphological change. Result:1. Changes of serum cytokine IL-1βcontent in each experiment group:The serum IL-1βcontent in the normal controlled group was 23.54±3.21 (pg/ml). In comparsion with the normal controlled group, the serum IL-1βcontent in the model self-healing group(47.35±2.91) was remarkably increased (P<0.01), and the refered treatment groups were also increased at different levels(P<0.01 or P<0.05), the respective content of IL-1βwere 33.10±5.76,32.28±7.21 27.38±3.03,29.57±6.2,33.83±6.46 (pg/ml). When compared to the normal controlled group, the content of IL-1βin DAA-I and Danshensu treatment group had a statistical significance, while the other treatment groups had no significant difference. In comparsion with the model self-healing group, each treatment group was obviously decreased(P<0.01); When compared to each other in the treatment groups, the serum IL-1βcontent in DAA-I and Danshensu treatment group was remarkably lower than that in valsartan treatment group.2. Changes of ICAM-1 gene expression in myocardial tissue of each experiment group:In comparsion with the normal controlled group (0.387±0.036), the expression of ICAM-1mRNA in the model self-healing group was remarkably increased (0.642±0.061, P<0.01), and the refered treatment group also had a remarkably increase(P<0.01). In comparsion with the model self-healing group, all the treatment groups were markly decreased at different levels (P<0.01 or P<0.05), the respective ICAM-1mRNA/β-actin were 0.538±0.041.0.517±0.045,0.475±0.054,0.502±0.052,0.557±0.039.When compared to each other in the treatment groups, the expression of ICAM-1mRNA in DAA-I and Danshensu treatment group was remarkably lower than that in valsartan treatment group (P<0.05), while the other treatment groups had no significant difference.3. In the normal controlled group, it can be seen that myocardial fiber arranged regularly, cardiac myocytes stained uniformly, form intact, structure clarity, cardiomyocytic gap close without edema or fibrosis, myocardial tissue normal without necrotic lesions or inflammatory cell infiltration; While in the mdel self-healing group, the myocardial injury can be seen obviously, including myocardial fiber arranged disorderly, cardiac myocytes uneven dyed enhanced, nuclear swelling, going round and even depigmentation, myocardial interstitial edema, cardiomyocytic gap widened, inflammatory cell extensively infiltrated with vascular dilated, congestive and bleeding, multiple myocardial fiber swelling and fractured, striated myocardium unclear or disappear,with local vacuolar degeneration etc. When compared with the model self-healing group, the myocardial injury in the refered treatment groups had improved in different degrees, and especially in DAA-I and Danshensu treatment group, the myocardial pathological infarction was ameliorated more obviously.Conclusion:1. The experimental myocardial ischemia injury rat model has been successfully replicated by the analysis of the changes in electrocardiogram and pathological morphology.2. DAA-I can obviously improve the myocardial ischemic injury induced by ISO, and the cardioprotective effect mechanism may be related to the inhibition of cytokines involved in inflammatory response pathway, such as the expression of IL-1βand ICAM-1.3. The early intervention with DAA-I may have a positive influence on the cardiovascular protective effect in the process of myocardial ischemia injury, the reason may be related to that it can reverse the adverse pathological effect of RAAS, and its function may be similar to the ARB.4. In the process of myocardial ischemia injury, single use of DAA-I,Danshensu and Valsartan can all significantly improve the inflammatory injury of myocardial ischemia. In addition, the combination use of DAA-I and Danshensu has a more pronounced synergistic effect in the inhibition of inflammatory response to myocardial ischemia injury, and it has a great significance for exploring a novel therapeutic method integrated traditional chinese medicine with western medicine in preventing and treating the cardiovascular diseases.
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