热休克基因表达对抗过氧化氢所致肺内皮细胞损伤的保护作用

The protective effect of heat shock gene expression against hydrogen peroxide一induced pulmonary endothelial cells injury

本研究探讨热休克反应（ｈｅａｔｓｈｏｃｋｒｅｓｐｏｎｓｅ，ＨｓＲ）对抗过氧化氢（Ｈ２Ｏ２）所致牛肺动脉内皮细胞（ＢＰＡＥＣｓ）损伤的保护作用及机制。实验发现，预先热休克处理（４２℃，２ｈ）可使ＢＰＡＥＣｓ中热休克蛋白７０ｋＤａ（ＨＳＰ７０）及ＨＳＰ７０ｍＲＮＡ明显增多，同时显著减轻Ｈ２Ｏ２所致的ＢＰＡＥＣｓ中乳酸脱氢酶释放和硫代巴比妥酸反应物含量增加及过氧化氢酶和超氧化物歧化酶活性的降低等变化。进一步实验证明放线菌酮和放线菌素Ｄ能分别抑制热休克诱导的Ｈ８Ｐ７０和ＨＳＰ７０ｍＲＮＡ的增多，同时均能取消ＨＳＲ对抗Ｈ２Ｏ２所致ＢＰＡＥＣｓ损伤的保护作用。结果提示，ＨＳＲ具有对抗Ｈ２Ｏ２所致ＢＰＡＥＣｓ损伤的保护作用；此种保护作用与细胞经热休克处理后细胞中热休克基因在转录和翻译两个水平的表达增强及抗氧化能力增加有关。

To ascertain whether heat shock gene expression could protect pulmonaryendothelial cell from hydrogen peroxide(H2O2)一indueed injury,the protective effect of HSPgene expression induced by pretreatment of bovine pulmonary endothelial eells(BPAECs)by heat shock (42 ℃, 2h)against lethal dose(lmmol·L(-1),45min) of H2O2一induced cyt-otoxieity was observed in vitro.It was found that BPAECs heat一shocked prior to exposureto H2O2(Immol·L(-1) 45min)showed significant decrease in H2O2一mediated incrementof LDH rdlease and TBARS production and had an obvious alleviation of H2O2一induccddecreased activities of catalase and superoxide dismutase. Further study showed thatcycloheximide, a protein synthesis inhibitor and Actinomycin D,a mRNA transcriptioninhibitor blocked the expression of HSP 70 and HSP 70 mRNA respectively.Both agentsprevented the cytoprotective effect of heat shock pretreatment against H2O2一mediatedBPAECs injury. The results suggested that HSP70 gene selectively translated after heat shockwas invoived in enhancement of eellular antioxidant mechanism and protected BPAECsagainst H2O2一induced injury