Protective Effects Of Esmolol On Lung And Intestinal Function In Septic Rats

Objective(1)To elucidate the protective effects of short-acting ?1 receptor blocker esmolol on lung injury in septic rats and to explore its mechanism.(2)To detect the protective effects of short-acting ?1 receptor blocker esmolol on intestinal injury in septic rats.Methods Seventy-two male Sprague-Dawley rats were randomly divided into three groups(n=24 each),sham operation group(Sham),sepsis group(CLP)and esmolol group(ES).Each group was randomly selected six rats for observing their survival time in seven days,and the remaining eighteen rats were randomly divided into three subgroups of 6h,12 h and 24 h,with six rats in each subgroup.The Sham group was treated with cecal exploratory surgery,while CLP and ES groups were treated with cecal ligation and puncture(CLP)to established sepsis model.Catheterization was performed on the left internal jugular vein after the model established.Saline of 1ml/h was continuously pumped into the Sham and the CLP group by micro pump for 6h;esmolol dilution 1ml/h(15mg /kg/h)was continuously pumped into the ES group for 6h.Rats in each subgroup were executed at 6h,12 h and 24 h after the operation,respectively.The plasma levels of CA,TNF-? and lung tissue NF-?B,intestinal tissue DAO,i-FABP were measured by ELISA.The expression levels of TLR4 and NF-?B protein in lung tissue were measured by Western Blot.The lung tissue protein content of alveolar lavage fluid,wet/dry weight ratio,lung coefficient and lung water content were measured.The pathological changes of lung and intestinal tissues were observed by an optical microscope.Results(1)the plasma levels of CA in CLP and ES groups at 6h after CLP were significantly increased compared with Sham group(P<0.05),and the plasma level of CA in ES group was increased significantly compared with Sham and CLP groups(P<0.05).At 12 h after CLP,plasma levels of CA in ES group was still significantly increased compared with Sham group(P<0.05);At 24 h after CLP,plasma levels of CA in ES group was increased significantly compared with CLP group(P<0.05).(2)At 6h,12 h and 24 h after CLP,CLP and ES groups plasma levels of NF-?B were significantly increased compared with Sham group(P<0.05),and ES group plasma levels of NF-?B was also significantly lower than the CLP group in each time point(P<0.05).(3)Western Blot results reveal: at 6h,12 h and 24 h after CLP,CLP and ES groups the expression of TLR4 and NF-?B protein in lung tissue were significantly increased compared with Sham group(P<0.05),and ES group the expression of TLR4 and NF-?B protein in lung tissue were also significantly lower than the CLP group in each time point(P<0.05).(4)At 6h,12 h and 24 h after CLP,CLP and ES groups plasma levels of TNF-? were significantly increased compared with Sham group(P<0.05),and ES group plasma levels of TNF-? was also significantly lower than the CLP group in each time point(P<0.05).(5)At 6h,12 h and 24 h after CLP,CLP and ES groups lung tissue wet/dry weight ratio,lung coefficient and lung water content,protein content of alveolar lavage fluid were significantly increased compared with Sham group(P<0.05),and ES group lung tissue wet/dry weight ratio,lung coefficient and lung water content,protein content of alveolar lavage fluid was also significantly lower than the CLP group in each time point(P<0.05).(6)At 6h,12 h and 24 h after CLP,CLP and ES groups intestinal tissue levels of DAO were significantly reduced compared with Sham group(P<0.05),and ES group intestinal tissue levels of DAO was also significantly higher than the CLP group in each time point(P<0.05).(7)At 6h,12 h and 24 h after CLP,CLP and ES groups intestinal tissue levels of i-FABP were significantly reduced compared with Sham group(P<0.05),and ES group intestinal tissue levels of i-FABP was also significantly higher than the CLP group in each time point(P<0.05).(8)Pathological changes of lung tissue: The pathological damage of Sham group was in the lightest degree,the CLP group in the most serious degree,and the pathological damage of ES group was significantly reduced compared with CLP group and was significantly increased compared with Sham group at all the time point.(9)Pathological changes of intestinal tissue: The pathological damage of Sham group was in the lightest degree,the CLP group in the most serious degree,and the pathological damage of ES group was significantly reduced compared with CLP group and was significantly increased compared with Sham group at all the time point.(10)Esmolol is able to prolong the survival time of rats with sepsis.Conclusions During the early stage of sepsis,there exit sympathetic nerve overstimulation,release of large amounts of catecholamines and inflammatory factors activation,which lead to lung and intestinal injury.Esmolol by promoting the secretion of catecholamine,inhibits the release of inflammatory cytokines,reduces lung and intestinal permeability,alleviayes pulmonary edema,protect the intestinal mucosal barrier,so as to protect the lungs and intestines function.Its mechanism is supposed to be as follows: Esmolol improves the reactivity of ? receptor to catecholamine,and regulates the level of inflammatory factors by inhibiting the signal path of TLR4—NF-?B—TNF-?,thus exerting protective effect on the lungs.