中国小儿急救医学
中國小兒急救醫學
중국소인급구의학
CHINESE PEDIATRIC EMERGENCY MEDICINE
2012年
5期
507-509
,共3页
脂多糖%内质网应激%线粒体%细胞凋亡%心肌细胞
脂多糖%內質網應激%線粒體%細胞凋亡%心肌細胞
지다당%내질망응격%선립체%세포조망%심기세포
Lipopolysaccharide%Endoplasmic reticulum stress%Mitochondria%Apoptosis%Cardiomyocytes
目的 研究脓毒症中内质网应激诱导心肌细胞凋亡的机制.方法 建立脂多糖(lipopolysacchride,LPS)H9C2心肌细胞脓毒症模型.通过实时定量聚合酶链反应(RTq-PCR)和流式细胞技术分别观察LPS干预H9C2心肌细胞24 h后的促凋亡蛋白CHOP mRNA、线粒体膜电位(mitochondrial membrane potential,MMP)和细胞凋亡的变化.使用内质网应激抑制剂Salubrinal预处理H9C2心肌细胞,观察以上指标变化.结果 LPS组CHOP mRNA表达(2.40±0.30)与对照组比较(1.00±0)显著上调(P＜0.05),LPS组MMP(1.07 ±0.33)与对照组(2.62±0.51)比较显著下降(P＜0.05),LPS组细胞凋亡率[(16.58±2.71)％]与对照组[(3.85±1.07)％]比较显著上升(P＜0.05).Salubrinal+ LPS组CHOP mRNA表达(1.60±0.23)与LPS组(2.40±0.30)比较显著下调(P＜0.05),Salubrinal+ LPS组MMP(1.85 ±0.31)与LPS组比较,显著上调(P＜0.05);Salubrinal+ LPS组细胞凋亡率[(6.05±1.48)％]与LPS组比较,显著下调(P＜0.05).结论 在H9C2心肌细胞脓毒症模型中,Salubrinal通过抑制LPS诱导CHOP mRNA的表达,减轻线粒体的损伤,从而降低心肌细胞凋亡率.脓毒症心肌细胞中内质网应激可能通过线粒体途径诱导细胞凋亡.
目的 研究膿毒癥中內質網應激誘導心肌細胞凋亡的機製.方法 建立脂多糖(lipopolysacchride,LPS)H9C2心肌細胞膿毒癥模型.通過實時定量聚閤酶鏈反應(RTq-PCR)和流式細胞技術分彆觀察LPS榦預H9C2心肌細胞24 h後的促凋亡蛋白CHOP mRNA、線粒體膜電位(mitochondrial membrane potential,MMP)和細胞凋亡的變化.使用內質網應激抑製劑Salubrinal預處理H9C2心肌細胞,觀察以上指標變化.結果 LPS組CHOP mRNA錶達(2.40±0.30)與對照組比較(1.00±0)顯著上調(P＜0.05),LPS組MMP(1.07 ±0.33)與對照組(2.62±0.51)比較顯著下降(P＜0.05),LPS組細胞凋亡率[(16.58±2.71)％]與對照組[(3.85±1.07)％]比較顯著上升(P＜0.05).Salubrinal+ LPS組CHOP mRNA錶達(1.60±0.23)與LPS組(2.40±0.30)比較顯著下調(P＜0.05),Salubrinal+ LPS組MMP(1.85 ±0.31)與LPS組比較,顯著上調(P＜0.05);Salubrinal+ LPS組細胞凋亡率[(6.05±1.48)％]與LPS組比較,顯著下調(P＜0.05).結論 在H9C2心肌細胞膿毒癥模型中,Salubrinal通過抑製LPS誘導CHOP mRNA的錶達,減輕線粒體的損傷,從而降低心肌細胞凋亡率.膿毒癥心肌細胞中內質網應激可能通過線粒體途徑誘導細胞凋亡.
목적 연구농독증중내질망응격유도심기세포조망적궤제.방법 건립지다당(lipopolysacchride,LPS)H9C2심기세포농독증모형.통과실시정량취합매련반응(RTq-PCR)화류식세포기술분별관찰LPS간예H9C2심기세포24 h후적촉조망단백CHOP mRNA、선립체막전위(mitochondrial membrane potential,MMP)화세포조망적변화.사용내질망응격억제제Salubrinal예처리H9C2심기세포,관찰이상지표변화.결과 LPS조CHOP mRNA표체(2.40±0.30)여대조조비교(1.00±0)현저상조(P＜0.05),LPS조MMP(1.07 ±0.33)여대조조(2.62±0.51)비교현저하강(P＜0.05),LPS조세포조망솔[(16.58±2.71)％]여대조조[(3.85±1.07)％]비교현저상승(P＜0.05).Salubrinal+ LPS조CHOP mRNA표체(1.60±0.23)여LPS조(2.40±0.30)비교현저하조(P＜0.05),Salubrinal+ LPS조MMP(1.85 ±0.31)여LPS조비교,현저상조(P＜0.05);Salubrinal+ LPS조세포조망솔[(6.05±1.48)％]여LPS조비교,현저하조(P＜0.05).결론 재H9C2심기세포농독증모형중,Salubrinal통과억제LPS유도CHOP mRNA적표체,감경선립체적손상,종이강저심기세포조망솔.농독증심기세포중내질망응격가능통과선립체도경유도세포조망.
Objective To investigate the mechanism of apoptosis induced by endoplasmic reticulum stress during sepsis.Methods Septic model of H9C2 cells was established by lipopolysaccharide (LPS).CHOP mRNA,mitochondrial membrane potential (MMP) and apoptosis were assessed by real-time PCR,flow cytometry respectively at LPS administration 24 h with or without salubrinal (inhibitor of endoplasmic reticulum stress).Results The expression of CHOP mRNA and apoptosis were upregulated,but MMP was decreased after LPS exposure 24 h compared with control group[2.40 ±0.30 vs 1.00 ±0,(16.58 ±2.71) ％ vs (3.85 ± 1.07) ％,1.07 ± 0.33 vs 2.62 ± 0.51,P ＜ 0.05).Compared with LPS group,salburinal pretreatment decreased LPS-induced upregulation of CHOP mRNA (1.60 ± 0.23 vs 2.40 ± 0.30,P ＜ 0.05),meanwhile,salburianl alleviated MMP(1.85 ± 0.31 vs 1.07 ± 0.33,P ＜ 0.05) and LPS-induced apoptosis [(6.05 ± 1.48) ％ vs (16.58 ± 2.71) ％,P ＜ 0.05].Conclusion Salubrinal plays a cytoprotective role against apoptosis induced by LPS through inhibition of CHOP mRNA,which leads to mitochondrial impairment.Endoplasmic reticulum stress may induce apoptosis via mitochondrial pathway in the septic model of H9C2 cardiomyocytes.
