Study Of TMP Treatment And Antioxidant Mechanism Effect On Myocardial Injury Induced By Sepsis

ObjectivesTo explore and discuss the effect of TMP on myocardial injury by sepsis and explore its possible mechanism both clinically and experimentally, so as to explore a new treating method for sepsis and contribute to the study of treating severe sepsis by combining both Chinese and western medicine.MethodsThis study includes clinical study and experimental research.Clinical study:Only patients with myocardial damage caused by sepsis were included in this study. All cases were chosen from ICU patients of Guangdong Provincial Hospital of TCM, who were admitted from January 2009 to December 2010. All the patients were diagnosed according to the ACCP/SCCM and were divided into treatment group (n=22) and control group(n=20). This study is a prospective, single-blind, randomized trial. All patients were treated by conventional treatment programs recommended by international sepsis treating guidelines. Patients of treatment group were also given intravenous TMP (80mg+GS/NS250ml, ivd, qd X 7 days), on the basis of conventional treatment.All patients were scored respectively according to APACHEII on the first day, third day, seventh day, and indexes of CTnI, BNP, MB (CK-MB), MDA and SOD were also tested and recorded at the three time points.Experimental study:SD male rats were selected and were made into sepsis model by CLP. Rats were randomly divided into 3 groups, sham operation group (n=18), sepsis group (n=36), TMP treatment group (n=36), within each group, there were three Subgroups marked by 24,48,72 hours. The rats' ventricular functions were observed by echocardiography, then blood samples taken from the abdominal aorta, cardiac tissue were given correlative detection. Indicators that were detected include:cardiac troponin (cTnI) levels, myocardial homogenate superoxide dismutase (SOD) and malondialdehyde (MDA),ResultClinical study section:1. myocardial enzymes and BNPBoth CTnI and BNP in the two groups were all significantly higher than normal before treatment. The difference between the two groups was not statistically important. At the times points of 3 days and 7 days after treatment, CTnI and BNP levels in both groups were decreased. CTnI and BNP levels in treatment group dropped more dramatically than that in control group, the difference was statistically significant(P<0.05). At the time points of 1 day,3 days and 7 days, CK-MB levels in both groups are normal, and there was no significant difference between the two groups.2. Oxidative stress indicatorsBefore treatment, comparison of MDA and SOD in both groups showed no statistical difference.3 days and 7 days after treatment, MDA in both groups decreased and SOD activity increased, the improvement in the treatment group was better than the control group, and the difference was statistically significant (P<0.05).3. APACHEII scoreComparison of APACHEII scores between the two groups before treatment, showed no significant difference. But after treatment, APACHEII scores in both groups decreased and the treatment group decreased more significantly compared with the control group, the difference was statistically significant (P <0.05).4. Safety EvaluationNo medicinal side effects were detected during the process of study. Detections of liver function, kidney function, hemoglutination function showed no medicine related unusual changes before and after the treatment.Experimental research section:1. mortalitySham rats had no death; mortality of three subgroups at three time points in CLP group were 33%,50% and 58%; CXQ group had a lower mortality than CLP group. But the difference among the three subgroups was not statistically significant (P> 0.05).2. cardiac functionThe comparison of cardiac functions in three groups before the operation showed no significant difference; The cardiac functions of rats in Sham group before and after operation had no significant changes, For CLP rats, their ejection fraction and left ventricular fractional shortening decreased while their cardiac output and heart rate increased, the differnce was statistically significant compared with the Sham group (P<0.05); compared with the CLP group, for rats in CXQ group, their ejection fraction and left ventricular fractional shortening were improved (P<0.05).3. troponinSerum troponin of CLP group increased after modeling compared with the Sham group, there was significant difference at all three time points (P<0.05); compared with the CLP group, serum troponin levels of rats in CXQ group were Lower than the CLP group. Comparing sub-groups at the time points of 24 and 48 hours in both CLP and CXQ groups, the difference was statistically significant (P<0.05).4. oxidative stress indicatorsAfter being modeled, myocardial SOD activity of rats in the CLP group decreased, compared with the Sham group, the difference among the subgroups at three time points was statistically significant(P<0.05); while compared with the CLP group, the drop of myocardial SOD activity in CXQ group was Lower than that of the CLP group, the difference of three subgroups at three time points was statistically significant(P<0.05).After being modeled, myocardial MDA in CLP group was significantly higher, comparing the sub-groups at 24 and 48 hours with that of Sham group, the difference was statistically significant (P<0.05); compared with the CLP group, the increase of MDA of rats in CXQ group was not as high as that of the CLP group. comparing the sub-groups at 24 and 48 hours with that of CLP group, the difference was statistically significant (P<0.05);5. Cardiac muscle morphological change For rats in Sham group, there was no denatured necrosis of myocardial cell; the striated cardiac muscle was clear and no inflammatory cell infiltration was detected.For rats in CLP group, their myocardial cell had pellet type denaturation, vacuole denaturation and fixity necrosis. The striated cardiac muscle was slurred, serious mesenchymal inflammation existed.For rats in CXQ group, their myocardial cell had only pellet type denaturation, the striated cardiac muscle was clear and only mild mesenchymal inflammation was found.ConclusionObservation of both clinical trials and animal experiments showed initially that TMP can reduce myocardial injury of patients with sepsis and improve cardiac function and reduce serum troponin. We think the possible mechanism may be related to the fact that TMP can reduce oxidative stress.