中国危重病急救医学
中國危重病急救醫學
중국위중병급구의학
CHINESE CRITICAL CARE MEDICINE
2009年
5期
270-273
,共4页
王云霞%皋源%田婕%李玮伟%王祥瑞
王雲霞%皋源%田婕%李瑋偉%王祥瑞
왕운하%고원%전첩%리위위%왕상서
羟乙基淀粉130/0.4%P38丝裂素活化蛋白激酶%急性肺损伤%炎症反应
羥乙基澱粉130/0.4%P38絲裂素活化蛋白激酶%急性肺損傷%炎癥反應
간을기정분130/0.4%P38사렬소활화단백격매%급성폐손상%염증반응
hydroxyethyl starch 130/0.4%P38 mitogen-activated protein kinases%acute lung injury%inflammation
目的 观察羟乙基淀粉130/0.4(万汶)对P38丝裂素活化蛋白激酶(MAPK)信号转导通路的影响,探讨其对感染所致急性肺损伤(ALI)保护作用的机制.方法 雄性SD大鼠30只,按随机数字表法分为正常对照组、脂多糖(LPS)组(LPS 10 mg/kg)、万汶15 ml/kg组(LPS l0 mg/kg+羟乙基淀粉130/0.415 ml/kg)、万汶30 ml/kg组(LPS 10 mg/kg+羟乙基淀粉130/0.4 30 ml/kg)及万汶对照组(羟乙基淀粉130/0.4 30 ml/kg),颈内静脉注入LPS 10 mg/kg复制ALI模型.6 h后处死大鼠,采集肺脏观察肺组织病理学变化;用蛋白质免疫印迹法(Western blotting)检测肺组织p-P38、P38、P-P44/42和P44/42的表达;用凝胶电迁移法(EMSA)检测活化蛋白l(AP-1)的DNA结合活性.结果 与正常对照组比较,LPs组表现为P38及P44/42的磷酸化水平增高,肺组织AP-l表达上升(P<0.05或P<0.01);万汶15 ml/kg和30 ml/kg均可抑制LPS导致的P38磷酸化(P均<0.05),同时可明显抑制AP-1的活性(P均<0.05);万汶两个剂量组间比较差异无统计学意义(P均>0.05).结论 羟乙基淀粉130/0.4通过抑制P38 MAPK信号转导通路中P38的磷酸化,进而使其下游的AP-1活性降低,减轻机体炎症反应.
目的 觀察羥乙基澱粉130/0.4(萬汶)對P38絲裂素活化蛋白激酶(MAPK)信號轉導通路的影響,探討其對感染所緻急性肺損傷(ALI)保護作用的機製.方法 雄性SD大鼠30隻,按隨機數字錶法分為正常對照組、脂多糖(LPS)組(LPS 10 mg/kg)、萬汶15 ml/kg組(LPS l0 mg/kg+羥乙基澱粉130/0.415 ml/kg)、萬汶30 ml/kg組(LPS 10 mg/kg+羥乙基澱粉130/0.4 30 ml/kg)及萬汶對照組(羥乙基澱粉130/0.4 30 ml/kg),頸內靜脈註入LPS 10 mg/kg複製ALI模型.6 h後處死大鼠,採集肺髒觀察肺組織病理學變化;用蛋白質免疫印跡法(Western blotting)檢測肺組織p-P38、P38、P-P44/42和P44/42的錶達;用凝膠電遷移法(EMSA)檢測活化蛋白l(AP-1)的DNA結閤活性.結果 與正常對照組比較,LPs組錶現為P38及P44/42的燐痠化水平增高,肺組織AP-l錶達上升(P<0.05或P<0.01);萬汶15 ml/kg和30 ml/kg均可抑製LPS導緻的P38燐痠化(P均<0.05),同時可明顯抑製AP-1的活性(P均<0.05);萬汶兩箇劑量組間比較差異無統計學意義(P均>0.05).結論 羥乙基澱粉130/0.4通過抑製P38 MAPK信號轉導通路中P38的燐痠化,進而使其下遊的AP-1活性降低,減輕機體炎癥反應.
목적 관찰간을기정분130/0.4(만문)대P38사렬소활화단백격매(MAPK)신호전도통로적영향,탐토기대감염소치급성폐손상(ALI)보호작용적궤제.방법 웅성SD대서30지,안수궤수자표법분위정상대조조、지다당(LPS)조(LPS 10 mg/kg)、만문15 ml/kg조(LPS l0 mg/kg+간을기정분130/0.415 ml/kg)、만문30 ml/kg조(LPS 10 mg/kg+간을기정분130/0.4 30 ml/kg)급만문대조조(간을기정분130/0.4 30 ml/kg),경내정맥주입LPS 10 mg/kg복제ALI모형.6 h후처사대서,채집폐장관찰폐조직병이학변화;용단백질면역인적법(Western blotting)검측폐조직p-P38、P38、P-P44/42화P44/42적표체;용응효전천이법(EMSA)검측활화단백l(AP-1)적DNA결합활성.결과 여정상대조조비교,LPs조표현위P38급P44/42적린산화수평증고,폐조직AP-l표체상승(P<0.05혹P<0.01);만문15 ml/kg화30 ml/kg균가억제LPS도치적P38린산화(P균<0.05),동시가명현억제AP-1적활성(P균<0.05);만문량개제량조간비교차이무통계학의의(P균>0.05).결론 간을기정분130/0.4통과억제P38 MAPK신호전도통로중P38적린산화,진이사기하유적AP-1활성강저,감경궤체염증반응.
Objective To observe the effect of hydroxyethyl starch 130/0.4(voluven)on P38 mitogen-activated protein kinases(MAPK)signal transduction pathway,with the aim of investigating the mechanism of its protective effect on acute lung injury(ALI)due to infection.Methods Thirty male Sprague-Dawley(SD)rats were randomly divided into control group,lipopolysaccharide(LPS 10 mg/kg) group,voluven groups(LPS 10 mg/kg,and hydroxyethyl starch 130/0.4 15 ml/kg or 30 ml/kg)and alone voluven grouP(hydroxyethyl starch 130/0.4 30 ml/kg),with 6 rats in each group.Rats were sacrificed at 6 hours,the lungs were harvested for observation of pathological changes.The expression of p-P38,P38, p-P44/42 and P44/42 were detected with Western blotting.Activating protein-1(AP-1)activation was measured with electrophoretie mobility shift assay(EMSA).Results Compared with control,p-P38, p-P44/42 and AP-1 were significantly higher in LPS group(P<0.05 or P<0.01).The expressions of p-P38 and AP-l activation were significantly reduced in both voluven groups(all P<0.05).But there was no statistically signifleant difference between voluven 15 ml/kg and 30 ml/kg groups(all P>0.05).Conclusion Hvdroxyethyl starch 130/0.4 can inhibit LPS-induced ALI by depressing expression of p-P38 and AP-1 activation in lung.
