摘要
目的探讨热休克蛋白70(HSP70)调控B淋巴细胞瘤-2(Bcl-2)表达抑制脓毒症大鼠肺血管内皮细胞损伤的机制。方法 SD大鼠30只随机分为对照组、脓毒症组、干预组,每组10只,脓毒症组腹腔注射20 mg/kg内毒素,干预组尾静脉注射溶于15 mL林格液的800μg重组质粒pcDNA3.1-HSP70,48 h后腹腔注射20 mg/kg内毒素;对照组腹腔注射等量生理盐水。24 h后采血检测各组大鼠血清IL-6、TNF-α水平,采血后将各组大鼠处死取其肺组织行苏木精-伊红(HE)染色,检测各组大鼠肺血管内皮细胞凋亡率,检测各组大鼠肺血管内皮细胞中HSP70、Bcl-2相关X蛋白(Bax)、Bcl-2蛋白表达水平。结果 HE染色结果显示干预组大鼠肺组织病理改变较模型组明显改善。脓毒症组大鼠肺血管内皮细胞凋亡率及血清IL-6、TNF-α水平显著高于对照组(P<0.05);干预组大鼠肺血管内皮细胞凋亡率及血清IL-6、TNF-α水平显著低于脓毒症组(P<0.05);脓毒症组大鼠肺血管内皮细胞中HSP70、Bax、Bcl-2蛋白表达水平显著高于对照组(P<0.05);干预组大鼠肺血管内皮细胞中HSP70、Bcl-2蛋白表达水平显著高于脓毒症组(P<0.05);干预组大鼠肺血管内皮细胞中Bax表达水平显著低于脓毒症组(P<0.05);干预组大鼠肺血管内皮细胞凋亡率及IL-6、TNF-α、HSP70、Bax、Bcl-2水平较对照组差异有统计学意义(P<0.05)。结论 HSP70可能通过下调Bax及上调Bcl-2表达,减轻脓毒症大鼠炎症反应,减少肺血管内皮细胞凋亡,抑制肺血管内皮细胞损伤,从而起到保护肺血管内皮细胞的作用,这可能成为脓毒症肺损伤治疗的新靶点。
Objective To investigate the mechanism of heat shock protein 70(HSP70)inhibiting pulmonary endothelial cell injury in rats with sepsis by regulating the expression of b-cell lymphocytoma-2(bcl-2).Methods 30 SD rats were randomly divided into control group,sepsis group and intervention group,with 10 rats in each group,and received the corresponding treatments. After 24 h,serum levels of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)were measured in each group. Pathological changes of lung tissue were observed by with hematoxylin-eosin(HE)staining. The apoptosis rate of pulmonary vascular endothelial cells in each group was detected. The expression levels of HSP70 and Bcl-2 related X protein(Bax)and Bcl-2 protein in lung vascular endothelial cells of each group were detected.Results HE staining results showed that the improvement of pathological changes of lung tissue in the intervention group was better than that of the model group. The apoptosis rate of serum vascular endothelial cells and the levels of serum IL-6 and TNF-α in the sepsis group were significantly higher than those in the control group(P < 0.05). The apoptosis rate of serum vascular endothelial cells and the levels of serum IL-6 and TNF-α in the intervention group were significantly higher than those in the sepsis group(P < 0.05). The expression levels of HSP70,Bax and Bcl-2 in pulmonary vascular endothelial cells of rats in sepsisgroup were significantly higher than those in control group(P < 0.05). The expression levels of HSP70 and Bcl-2 in pulmo-nary vascular endothelial cells in intervention group were significantly higher than those in sepsis group(P < 0.05). The expression of Bax in pulmonary vascular endothelial cells in intervention group was significantly lower than that in sepsisgroup(P < 0.05). The apoptotic rate of pulmonary vascular endothelial cells and the levels of IL-6,TNF-a,HSP70,Bax and Bcl-2 in the intervention group were significantly different from those in the control group(P < 0.05).Conclusion The protective effect of HSP70 on pulmonary vascular endothelial cells is related to the down-regulation of Bax,the up-regulation of bcl-2 expression,the reduction of inflammatory response,the reduction of cell apoptosis,and the inhibition of cell injury in sepsis rats,which may become a new target for the treatment of pulmonary vascular injury in sepsis.
作者
陈雅静
许磊
郭东风
陈果
袁晓燕
刘国荣
杭敏
王佩
罗娅娟
CHEN Yajing;XU Lei;GUO Dong⁃feng;Fruit Chan;YUAN Xiao⁃yan;LIU Guo⁃rong;HANG Min;WANG Pei;LUO Ya⁃juan(Emergency Department,Gongli Hospital,Pudong New District,Shanghai City,200135,China)
出处
《解剖学研究》
CAS
2020年第3期258-261,267,共5页
Anatomy Research
基金
上海市浦东新区公利医院人才培养计划(GLRq2018-03)
浦东新区卫生系统重点专科(PWZzk2017-05)
浦东新区卫生计生2018年度青年科技项目(PW2018B-03)
作者简介
通信作者:许磊,E⁃mail:ddddsbd111@sina.com
