1.Taurine and Angiotensin-converting Enzyme Inhibitor: the Protective Effect on Acute Lung Injury2.Analysis of Influential Factors in ALI/ARDS
|School||Chongqing Medical University|
|Keywords||taurine angiotensin-converting enzyme inhibitior acutelung injury endothelial cellNingxia ALI/ARDS influential factors|
Objective:Acute lung injury is a critical illness syndrome consisting of acuteprogressive hypoxemic respiratory failure arising either from a variety ofdirect (pulmonary) or indirect (extrapulmonary) insults. Duing to thecomplex lung injury pathophysiology of ALI, it remains underdiagnosed andundertreated. At present，therapeutic interventions to treat ALI remainlimited. Mortality from ALI is substantial. To observe lung pathophysiologyand endothelial activation and injury in rats with ALI, we established theanimal model of ALI by intraperitoneal injection of mindose of LPS inadvance combined with intravenous injection of LPS. Therefore toinvestigate the protective effect by taurine and angiotensin convertingenzyme inhibitor on acute lung injury and its relative mechanism, we treatedrats with ALI by intraperitoneal injection of taurine, captopril，and both durgrespectively.Methods:1Subgrop:126male SD rats were randomly divided into five groups: (1) normal control group (n=6).(2) acute lung injury (LPS) group: ratswere divided into five time points at3h,6h,9h,12h,24h after intravenousinjection of LPS and there were6rats in every time point (n=6);(3) thetaurine group: rats were divided into above-mentioned five time points afterintravenous injection of LPS and there were6rats in every time point (n=6);(4) the captopril group: rats were divided into above-mentioned five timepoints after intravenous injection of LPS and there were6rats in every timepoint (n=6),(5) the taurine and the captopril group: rats were divided intoabove-mentioned five time points after intravenous injection of LPS andthere were6rats in every time point (n=6).2Estabished ALI model: Rats were pre-activated by intraperitonealinjection of LPS(0.5mg/kg) in advance. Then after pre-activating for12hours, rats were induced by intravenous injection of LPS (5mg/kg.).Specimens were collected after intravenous injection of LPS at five timepoint.3The normal control group and treatment group:(1) The normalcontrol group: Intraperitoneal injection of saline for12hours, saline wasinjected intravenously.(2) The taurine group: After LPS preactivating for12hours, taurine50mg/kg was injected intraperitoneally and LPS was injectedintravenously.(3) The captopril group:After LPS pre-activating for12hours,captopril1.25mg/kg was injected intraperitoneally and LPS was injectedintravenously.(4)The taurine and captopril group: After LPS preactivating for12hours, taurine50mg/kg and the captopril1.25mg/kg were injectedintraperitoneally and LPS was injected intravenously. Specimens werecollected at3h after intravenous injection of saline in normal group and at3h,6h,9h,12h,24h time point after intravenous injection of LPS in alltreatment group respectively.4Measurement: Measurement of lung wet-dry weight and arterialpartial pressure of oxygen (PaO2). Lung histopathology were observed andanalyzed. Von Willebrand factor (vWF), endothelin-1(ET-1), Solubleintercellular adhesion molecule-1(sICAM-1), thrombomodulin (TM),platelet-activating factor (PAF) levels were detected in plasma andbronchoalveolar lavage fluid (BALF) by ELISA.5Statistical Analysis: Data are expressed as mean±SD. Statisticalanalyses was done using SPSS11.5statistical software. Statisticaldifferences between the data were determined with one-way analysis ofvariance and mutltiple comparisons were tested withStudent-Newman-Keuls-test(SNK), and a P value,0.05was consideredsignificant.Resuls:1Lung wet-dry weight ratio: Lung W/D ratio showed a significantincreasing in lung injury group（P<0.05）, and it increased obviously at12h、24h time point. Lung W/D ratio decreased in varying degrees in taurinegroup, captopril group and taurine and captopril group, but still higher than the normal group（P<0.05）. The decreasing mostly is in the combinedtreatment group.2Arterial partial pressure of oxygen (PaO2) levels: PaO2levels in thelung injury group were significantly lower than the control group（P<0.05）,but increased in taurine group and captopril group, and increased mostsignificantly after the combined treatment intervention（P<0.05）and it wasobvious at9h、12h、24h time point.3Lung histology: Lung injury group showed marked inflammation andmild lung edema with marked thickening of alveolar septa and alveolarspace narrowing. Improved the pathological changes were observed in thetaurine group, captopril group and both combined. The score of lung injury:the score of lung injury in the acute lung injury group were significantlyhigher than the normal group and decreased in taurine group and captoprilgroup and both combined group（P<0.05）,and decreased mostsignificantly after the combined treatment intervention. It improvedobviously at9h、12h、24h time point4The plasma levels of vWF，ET-1, sICAM-1, TM and PAF：Theplasma levels of vWF，ET-1, sICAM-1, TM and PAF were increased in lunginjury group than in the control group（P<0.05）. Most of them wereimproved at3h,6h,9h time point obviously. But after the intervention, theywere lower in taurine treatment group, captopril group, and both treantmentgroup at the most of different time point than in the acute lung injury group（P<0.05）. The levels of them in the joint intervention were lowerthan the lung injury group obviously.5The BLAF levels of vWF，ET-1, sICAM-1, TM and PAF：TheBLAF levels of vWF,ET-1, sICAM-1, TM and PAF were increased in lunginjury group than in the control group at the different time point andincreased obviously at3h、6h、9h time point. After the treatment, they werelower in taurine treatment group, captopril group, and both treantment groupat the most of different time point than in acute lung injury group. Thelevels of them in the joint intervention group were lower than the lung injurygroup obviously and were still a little higer than the normal control group.Conclusion:1We successfully established the animal model of ALI byintra-peritoneal injection of mindose of LPS in advance combined withint-ravenous injection of LPS. It was porved by the increasing lung wet-dryweight ratio, the decreasing PaO2levels, the changes of Lung histology andthe increasing score of lung injury. The way of making animal model isrelatively rare at present.2There was lung endothelial cell activation and injury in ALI and itwas expressed by the increasing levels of plasma and BLAF vWF，ET-1,sICAM-1, TM and PAF which represented the lung endothelial cellactivation and injury.3Taurine had a protective effect on acute lung injury and the i-njuried pulmonary vascular endothelial cells.4Angiotensin-converting enzyme inhibitors had protective effect onacute lung injury and the injuried pulmonary vascular endothelial cells.5It prompted that two-drug combination had a more protective effecton lung injury and pulmonary vascular endothelial cells, and it was betterthan single drug-intervention group. The study showed that we can treat ALIwith joint treatment of taurine and captopril. The treatment of these twodrugs combination on ALI was not reported in domestic at present. Objective:To recognize and prevent the clinical influential factors in ALI/ARDSearly, reduce mortality and improve the cure rate, we collected the clinicaldata of patients with ALI/ARDS in ICU of Ningxia Medical UniversityGeneral Hospital and analyzed the influential factors that led to ALI/ARDS,affected disease progression and prognosis.Method:The clinical data of375patients from March2010to December2012were retrospectively analyzed. The patients were divided into three groups.①the initial diagnosis of ALI group and the initial diagnosis of ARDSgroup.②ALI improved group and ALI aggravated into ARDS group.③thesurvivor group of ARDS and the non-survivor group of ARDS. Etiology,age, gender, chronic disease, acute organ dysfunction, blood-gas analysis,APACHEII score of patients in theses three groups within24hours ofdiagnosis were analyzed. Statistical analyses was done using SPSS11.5statistical software. Data are expressed as mean±SD. All data were analyzedby univariate test, one-way analysis of variance and multiple logistic regression method.Results:1154patients(3.73%) developed initial diagnosis of ALI and221patients (5.36%) met criteria for initial diagnosis of ARDS in all4125patients.Total constituent ratio of ALI/ARDS was9.09%.18patients diedand mortality was11.69%%in ALI.118patients died and mortality was53.40%in ARDS. Total mortality was36.27%.2There were41female (26.62%) and113male (73.38%) patients inALI. The mean age was51.05±18.03. Lung injury occurred most commonlyin the setting of trauma(58/154;37.66%), infection (45/154;29.22%),complicating chronic disease (36/154;24.68%）, and complicating morethan three acute organ dysfunction（39/154;25.32%）. The mean score ofAPACHEII was16.47±7.79and the mean hospital day was13.86±13.54days.3There were61female (27.6%) and160male (73.38%) patients inARDS. The mean age was53.57±16.38. Lung injury occurred mostcommonly in the setting of trauma(93/221;42.08%), infection (109/221;49.32%), complicating chronic disease (77/221;34.8%), and complicatingmore than three acute organ dysfunction（101/221;45.70%）. The meanscore of APACHEII was16.77±6.80and the mean hospital day was14.28±12.57days.4The initial diagnosis of ALI and ARDS group: pneumonia (P<0.001), septic shock (P=0.008), infection of other parts except for lung (p=0.015),post operation （P<0.001）, unexplained （P=0.001） were statisticalsingnificance from etiology. And no factors included into this study reachedstatistical singnificance from the multivariater logistic regression.5The initial diagnosis of ALI improved group and aggravated intoARDS group: pneumonia (P<0.001), sepsis (p=0.008), septicshock(P=0.011), post operation（P<0.001, unexplained（P=0.001）reachedstatistical singnificancein etiology. Acute circulatory systemdysfunction(P=0.016), acute liver system disfunction(p=0.004), acutenervous system disfunction(p=0.006), pH value(p=0.038) are statisticalsingnificantfrom the multivariater logistic regression.6The survivor group and the non-survivor group of ARDS:trauma(p=0.004), pneumonia(p=0.006), septic shock(p=0.013),unexplained(p=0.040) are statistical singnificant in etiology. Andage(p<0.001), acute circulatory system disfunction(P=0.001), PCO2(P=0.005) are statistical singnificant from the multivariater logisticregression.Conclusion:1The constituent ratio was3.73%in initial diagnosis of ALI and5.36%in the initial diagnosis of ARDS. Total constituent ratio ofALI/ARDS was9.09%in Ningxia. The mortality was11.69%in ALI andwas53.40%in ARDS. Total mortality was36.27%in Ningxia. ALI/ARDS was developed in male and older people. Lung injury occurred mostcommonly in the setting of trauma and infection. There was a high score ofAPACHEII and hospital day was commonly more than ten days.2Infection of other parts except for lung, post operation, unexplainedreasons are tend to induce ALI. Pneumonia and septic shock are morelikely to induce ARDS.ALI induced by pneumonia and post operation has abetter improvement rate and prognosis, yet ALI induced by septic shockand sepsis has a poor prognosis, and is tend to aggravate into ARDS. ARDSinduced by traumah as a better prognosis, relatively, ARDS induced bypneumonia, septic shock has a poor prognosis.3Acute circulatory system dysfunction, acute liver system dysfunction,acute nervous system dysfunction, pH value may be the independent riskfactors for ALI aggravating into ARDS. There was a significant badinfluence upon the development and poor prognosis of ALI/ARDS whenthe patients complicated more than three acute organ dysfunction.4Age, acute circulatory system dysfunction, PaCO2may be theindependent risk factors for ARDS.