The Experimental Study On The Early Intervention Effects Of Valsartan On Endotoxemia In Rat

Objective The purpose of this study is to investigate the early intervention effects of angiotensinⅡreceptor blocker(valsartan) on endotoxemia in ratMaterial and methods 60 rats were divided randomly into ten groups ,namely normal control group(A),model group(B1(2h),B2(4h),B3(8h)),valsartan group(C1(2h),C2(4h),C3(8h)) ,physiologic saline group(D1(2h),D2(4h),D3(8h)). The rats of model group were given LPS(3mg/kg) through peritoneal injection. The rats of valsartan group were lavaged with valsartan(5mg/kg) ten minites after LPS were injected through peritoneal,while the rats of physiologic saline group were lavaged with physiologic saline pt aequ .The rats were executed at corresponding time after LPS were injected through peritoneal,then drew blood from heart quickly and took some organ tissues including heart,liver,lung,kidney,small intestine.Detected the concentration of TNF-α,VEGF,L-selectin in serum by ELISA.The pathologic changes of organ tissues were examined with optical microscope.Results When the rats were given LPS through peritoneal injection,the concentration of TNF-αin serum raised quickly, and reached peak after two hours(P<0.01).It was still higher significantly than normal after four hours (P<0.01).It degraded to normal after eight hours (P>0.05).In the valsartan group,the concentration of TNF-αin serum reached peak after two hours also,but the peak value decreased notably(P<0.05).The concentration of VEGF in serum increased progressively with time prolong after LPS was injected through peritoneal,and the difference was obviouse at LPS2h when compared with normal(P<0.01).The concentration of sL-selectin in serum increased after the rats were given LPS,and reached peak value after four hours(P<0.01).The mean after eight hours decreased compared with that after four hours,but have no significance in statistics(P>0.05).The pathological lesion in organs aggravated with time prolong. The concentration of VEGF and sL-selectin in serum decreased obviously in valsartan group compared with model group (P<0.05),and the degree of pathological lesion were lessened in valsartan group.Conclusion After the rats were given LPS through peritoneal injection,they presented some appearance .For example, fervescence, accelerated breathing, depressed, few actions and so on.The concentration of TNF-α,VEGF and sL-selectin in serum increased,moreover, pathological lesion appeared in some major organs and aggravated with time prolong. So the preparation of endotoxemia model was successful.TNF-αis an fast reaction factor,with the infection time prolong,organism educe regulation role through activating negative feedback mechanism.The concentration of VEGF increased with time prolong.It indicate that VEGF correlate with the extent of pathogenetic condition.The concentration of sL-selectin increased at early stage of acute inflammation,indicating that the quantity of activated leukocyte increased.After the concentration reaching peak value,it keep high level to prevent leukocyte to activate competively .High concentration of sL-selectin can educe negative feedback immunoloregulation role, amendment excessive systemic inflammatory response. Valsartan can decrease the level of TNF-α,VEGF and sL-selectin in endotoxemia. It lessen systemic inflammatory response by reducing the dilivery of mediators of inflammation and inhibiting the leukocytes to activate excessively and decrease the capillary permeability.Moreover,it has protection for organs.