Stuty On Protective Effects And Its Mechanism Of Tetrathylpyrazine On Myocardial And Kidney'S Injury In The Rats In The Early Stage After Severe Thermal Injury

Part1To investigate protective effects of Tetrathylpyrazine on myocardium and kidney's Ultrastructure injury in rats in the early stage after severe thermal injuryObjective and significanceThere is occurred cardiac and kidney's dysfunction in the early stageafter severe thermal injury. The heart is an organ that needs consumingmuch more oxygen and a extremely sensitive organ to hypoxia .There is amaximum blood flow through kidney. By recently many researches haveshowed there is lack blood flow and oxygen in myocardium and kidneyfollowing severe postburn 1h, so it may cause abnormal change ofmyocardium's and kidney's Ultrastructure and cardiac enzyme and cardiactroponin I(cTnI) leakage from cytoplasm。To investigate whether cardiacand kidney's dysfunction have relations with abnormal Ultrastructurechange of myocardium and kidney and cardiac enzyme and cardiactroponin I(cTnI) leakage and Cr and Tetrathylpyrazine improvesmechanism of myocardial and kidney's injury in the rats in the early stageafter severe thermal injuryMaterials and Methods One hundred and four adult health rats were randomly divided intothree groups: sham group(A group),burn group(B group) and burn + TMPgroup (C group). both of B and C groups were 48 respectively and wereanesthetized with intraperitoneal injection of pentobarbital sodium(30mg/kg body weight), and a third-degree scald burn 30% total bodysurface area on the back was produced with 92℃water for 18 secondsaccording to the pathology, and fluid resuscitated (4 ml/kg per %burn oflactated Ringer solution) by Parkland formula through an intraperitonealinjection, at the same time C group were injected TMP (20mg/kg bodyweight).At six scheduled time points(1,3,6,12,24,48 hours postburns),third groups animals'blood samples were drawn for determination ofcardiac troponin I , CK-MB, LDH and Cr and myocardium's and kidney'sultrastructure.Result That the levels of cTn I , CK-MB, LDH in serum increase to speed upat 6 hour postburn in the of group B and the levels of highest ones were at12 hours, at 48 hours the results were still abnormal that were compared togroup A(P<0.05). The levels of cTn I , CK-MB, LDH in serum of groupC were lower than the levels of group B(P<0.05). The chang of levels of Crin serum were slighter . In the group B the abnormal change of cardiac andkidney's Ultrastructure starts at 6 hours, the severe change is at 12 hours,but the injury of group C is slighter than that of group B(P<0.05).Conclusion There are obvious injury in cardiac and kidney's tissue in rats in theearly stage after severe thermal injury. TMP can obvious lighten theabnormal change of cardiac and kidney's ultrastructure and improve heartand kibney's function in the early stage after severe thermal injury.Part2Study on regulating effects of Tetrathylpyrazine on cytokine, inflammatory medium in the rats in the early stage after severe thermal injuryObjective and significance To investigate whether cardiac and kidney's dysfunction and injuryhave relations with the ratio of NO2 /ET, CGRP/ET and the levels of -SOD,MDA,TNF-αin serum and the levels of TNF-αCa2+ in kidney'sand cardiac tissue. To study whether TMP may regulate the ratio ofNO2 /ET,CGRP/ET and the levels of SOD,MDA,TNF-αin serum and the -levels of TNF-αCa2+ in kidney's and cardiac tissue and protect andimprove cardiac and kidney's function in rats of In the early stage aftersevere thermal injury.Materials and Methods One hundred and four adult health rats were randomly divided intothree groups: sham group(A group),burn group(B group) and burn + TMPgroup (C group). both of B and C groups were 48 respectively and wereanesthetized with intraperitoneal injection of pentobarbital sodium(30mg/kg body weight), and a 30%third-degree scald burns on the backwas produced wih 92℃water for 18 seconds according to the pathology,animals were resuscitated with an intraperitoneal injection of an amount oflactic acid Ringer'solution by Parkland formula ,at the same time C groupwere injected TMP (20mg/kg body weight).At six scheduled timepoints(1,3,6,12,24,48 hours postburn), third groups animals'blood sampleswere drawn for determination of the levels of NO, ET, CGRP and SOD,MDA, TNF-αin serum and the levels of TNF-αCa2+ in kidney's andcardiac tissue .Result That the ratios of NO2 /ET, CGRP/ET and the levels of SOD decrease -to speed up in serum at 6 hour postburn in the group B and the lowestratios and levels were at 12 hours, at 48 hours the results were stillabnormal that were compared to group A(P<0.05-0.01). The ratios ofNO2 /ET, CGRP/ET and the levels of SOD of group C were higher than the -ratios and levels of group B(P<0.05) . The levels of MDA,TNF-αinserum and the levels of TNF-αand Ca2+ in kidney's and cardiac tissueincrease to speed up at 6 hour postburn in the group B and the levels ofhighest ones were at 12 hours, at 48 hours the results were still abnormalthat were compared to group A(P<0.05). The levels of MDA,TNF-αinserum and the levels of TNF-αand Ca2+ in kidney's and cardiac tissue ofgroup C were lower than the levels of group B(P<0.05).Conclusion Dysfunction and injury of heart and kidneys that have relations withthe descend of the ratio of NO2 /ET, CGRP/ET and levels of SOD and the -ascension of the levels of MDA,TNF-αin serum and the levels of TNF-αCa2+ in kidney's and cardiac tissue. TMP can modulate the ratio ofNO2-/ET,CGRP/ET and the levels of SOD,MDA,TNF-αin serum and thelevels of TNF-αCa2+ in kidney's and cardiac tissue and protects cardiacand kidney's function in rats of In the early stage after severe thermalinjury.Part3To study on regulating effect of TMP on the myocardium and kidney'Sexpression and activation of p38MAPK,TNF-αmRNA, Ultrastructurechanges in rats in the early stage after severe thermal injuryObjective and significance To investigate whether p38MAPK,P-p38MAPK and TNF-αhaverelations with cardiac and kidney's dysfunction and injury and TMP mayreduce the expression and activation of p38MAPK , P-p38MAPK andTNF-αmRNA and comes into being the protective process on themyocardium kidnys in rats in the early stage after severe thermal injury.Methods One hundred and fifty tow adult health rats were randomly dividedinto three groups: sham group(group A),burn group(group B) , burn + TMPgroup (group C), SB group(group D), B , C and D groups were dividedinto six scheduled time points(1,3,6,12,24,48 hours postburn);We check onthe expression and activation levels of p38MAPK, P-p38MAPK and TNF-αmRNA in the tissue of myocardium and kidney and change ofUltrastructure in myocardium and kidney in rats.Results In the group B a lot of expreesion and activation and nucleusdisplacement of p38MAPK and P-p38MAPK in cardiocyte and kideny'stissue and cell were at 1 hour postburn, the highest ones were at 3 hours.The expressing levels of TNF-αmRNA in myocardium and kideny's tissuestart to increase at 6 hours and the level of highest one is at 12 hours, thelevel is still high at 24 and 48 hours. The abnormal change of ultrastructurestarts at 6 hours, the severe change is at 12 hours , but the expreesion andactivation of p38MAPK and TNF-αmRNA and ultrastructure injurygroups of C and D were slighter than that of burn group B.Conclusion There are over expression and activation of p38MAPK, P-p38MAPKand TNF-αmRNA in myocardium and kideny's tissue in rats in the earlystage after severe thermal injury ,that TMP improves and protects heartfunction that maybe results from reducing the expression of p38MAPK,P-p38MAPK and TNF-αmRNA.