CAJ | 학술논문

目的观察过氧化物酶增殖体激活受体β对失血性休克大鼠急性肺损伤的保护作用及机制.方法复制失血性休克大鼠ALI模型,随机(随机数字法)将96只SD大鼠分为5组,每组分为1h、2h、4h、6h四个时相点,每个时相点6只老鼠.观察记录在1、2、4、6h取肺组织测定PPARβ受体表达,行病理学检查、肺干湿重比系数作为检测肺损伤程度的指标;检测肺组织超氧化物酶SOD、GSH-Px活性氧化产物8-iso-PGF2α含量来评估机体氧化应激状态.然后,给予PPARβ受体拮抗剂(GSK 0660)进行预处理,观察其对失血性休克所致急性肺损伤过程中后动物各项指标的影响,并初步探讨炎症因子、氧化抗氧化系统及细胞凋亡在其中的作用.结果 ①失血性休克致伤组大鼠超氧化物酶SOD、GSH-Px活性较假手术组显著升高(P＜0.01).②GW0742激活剂使ALI肺组织中超氧化物酶SOD、GSH-Px活性在各时相点较单纯失血性休克致伤组有不同程度降低,以2h、4h升高最显著(P＜0.01).③单独使用GW0742能改善PaO2、大鼠肺组织W/D比值、肺组织病理积分,抑制肺组织SOD、GSH-Px活性(P＜0.01)及降低8-iso-PGF2α的含量;使用拮抗剂GSK0660使上述作用减轻(P＜0.叭).结论 ①失血性休克ALI大鼠模型,肺组织SOD、GSH-Px活性显著升高,提示失血性休克处于急性氧化应激状态.②GW0742能显著上调ALI大鼠肺组织SOD、GSH-Px的活性,降低氧化产物8-iso-PGF2α的含量.③推测GW0742通过可能通过抑制TNF-α基因和蛋白的表达,降低肺组织SOD活性对ALI肺组织起到一定程度的保护作用,减轻ALI肺组织的炎症,改善PaO2,可能是通过阻止NF-κB的活化起作用的.
목적 관찰과양화물매증식체격활수체β대실혈성휴극대서급성폐손상적보호작용급궤제.방법 복제실혈성휴극대서ALI모형,수궤(수궤수자법)장96지SD대서분위5조,매조분위1h、2h、4h、6h사개시상점,매개시상점6지로서.관찰기록재1、2、4、6h취폐조직측정PPARβ수체표체,행병이학검사、폐간습중비계수작위검측폐손상정도적지표;검측폐조직초양화물매SOD、GSH-Px활성양화산물8-iso-PGF2α함량래평고궤체양화응격상태.연후,급여PPARβ수체길항제(GSK 0660)진행예처리,관찰기대실혈성휴극소치급성폐손상과정중후동물각항지표적영향,병초보탐토염증인자、양화항양화계통급세포조망재기중적작용.결과 ①실혈성휴극치상조대서초양화물매SOD、GSH-Px활성교가수술조현저승고(P＜0.01).②GW0742격활제사ALI폐조직중초양화물매SOD、GSH-Px활성재각시상점교단순실혈성휴극치상조유불동정도강저,이2h、4h승고최현저(P＜0.01).③단독사용GW0742능개선PaO2、대서폐조직W/D비치、폐조직병리적분,억제폐조직SOD、GSH-Px활성(P＜0.01)급강저8-iso-PGF2α적함량;사용길항제GSK0660사상술작용감경(P＜0.팔).결론 ①실혈성휴극ALI대서모형,폐조직SOD、GSH-Px활성현저승고,제시실혈성휴극처우급성양화응격상태.②GW0742능현저상조ALI대서폐조직SOD、GSH-Px적활성,강저양화산물8-iso-PGF2α적함량.③추측GW0742통과가능통과억제TNF-α기인화단백적표체,강저폐조직SOD활성대ALI폐조직기도일정정도적보호작용,감경ALI폐조직적염증,개선PaO2,가능시통과조지NF-κB적활화기작용적.
Objective To observe the protective effects of peroxisome proliferation activated receptorβ (PPAR-b) on acute lung injury in the wake of hemorrhagic shock in rats in order to illuminate the mechanism.Methods After ALI model of rat was established following hemorrhagic shock,96 SD rats were divided randomly (random number) into 4 groups:group A (sham operation group),group B (ALI group),group C (GSK0660,an antagonist to PPAR-b given prior to exsanguinations for pretreatment) and group D (GW0742,an agonist of PPAR-b given before exsanguinations for pretreatment).Each group was further divided into 1 h,2 h,4 h and 6 h subgroups.Six mice of each subgroup were sacrificed at each interval.Expression of PPAR-β receptor in lung tissues was detected at 1 h,2 h,4 h and 6 hours.Pathological examination and lung wet/dry weight ratio were detected,and lung tissue antioxidant enzyme SOD and 8-iso-PGF2α,the oxidation product of activated GSH-Px were evaluated.Results (①)Antioxidant enzymes SOD and activated GSH-Px were significantly higher in ALI group than those in the sham operation group (P＜0.01).(②Tne antioxidant enzyme SOD and activated GSH-Px in lung tissue in GW0742 group decreased at each interval especially at 2 h and4 h compared with ALI group (P ＜0.01).(③) GW0742 used alone can improvePaO2,W/D ratio of lung tissue of rats,lung pathology integral,and inhibit the activity of SOD and GSH-Px in lung tissue (P ＜ 0.01) and decrease the content of 8-iso-PGF-2α.The antagonist GSK0660 can lessen the above effects (P ＜ 0.01).Conclusions (①)ALI emerged from hemorrhagic shock in rats leading to significantly increased activity of SOD and GSH-Px in lung tissue,suggesting rats subjected to acute oxidative stress.(②)GW0742 can up-regulate the levels of SOD and GSH-Px in lung tissue of rats with ALI.It also decreased the content of 8-iso-PGF2 α,the oxidation products of GSH-Px.(③) It was suggested that GW0742 might inhibit the expression of TNF-α mRNA and level of TNF-a protein,and decreased SOD activity in lung tissue,protecting lung tissue to some degree from ALI and improving PaO2.The mechanism of it may be attributed to preventing NF-κ B activation.