南方医科大学学报 ›› 2014, Vol. 34 ›› Issue (12): 1804-.

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大鼠脑皮质内质网应激及凋亡相关因子在控制性低血压中的变化

张建杏,李红英,周国斌,王研   

  • 出版日期:2014-12-20 发布日期:2014-12-20

Changes of endoplasmic reticulum stress- and apoptosis-related factors in rat cerebral
cortex following controlled hypotension

  • Online:2014-12-20 Published:2014-12-20

摘要: 目的探讨在不同程度控制性低血压中大鼠脑皮质神经元内质网应激(ERS)及凋亡的变化。方法24只SD雄性大鼠随机
均分为A组(对照组)、B组(70 mmHg)、C组(50 mmHg)、D组(30 mmHg)四组。大鼠麻醉后用硝普钠复合艾司络尔诱导控制性
低血压,达到目的血压后维持60 min。对照组无降压,各组大鼠最终补液量相等。控制性低血压完成后12 h断头取脑,western
blot法检测脑皮质中Bax、Bcl-2、GRP78、CHOP、caspase-12表达,RT-PCR法检测脑皮质GRP78 mRNA表达,TUNEL法检测皮
质神经元凋亡。结果与A组比较,C组及D组中ERS相关因子GRP78 mRNA,GRP78、CHOP、caspase-12蛋白表达明显增加且
组间有统计学差异(P<0.05),在B组未见明显变化(P>0.05);与A组比较,C组及D组中凋亡细胞数明显增加,Bax表达上调,
Bcl-2表达下调(P<0.05),在B组未见明显变化(P>0.05)。结论轻度的控制性低血压(70 mmHg)不会引起脑皮质神经元损伤,
而程度较重的控制性低血压(低于50 mmHg)可以诱导脑皮质神经元ERS及凋亡。

Abstract: Objective To investigate the changes of endoplasmic reticulum stress (ERS)- and apoptosis-related factors in rat
cerebral cortex following controlled hypotension. Methods Twenty-four healthy male SD rats were randomly divided into 4
equal groups, including a sham hypotension group (group A) and 3 hypotension groups with the mean arterial pressure
maintained for 60 min at 70 mmHg (group B), 50 mmHg (group) and 30 mmHg (group D) with sodium nitroprusside and
esmolol. All the rats received an equal volume of fluid infusion. Twelve hours after controlled hypotension, the rats were
sacrificed to examine the protein expressions of Bax, Bcl-2, glucose-regulated protein 78 (GRP78), C/EBP homologous protein
(CHOP) and caspase-12 in the cortex with Western blotting. GRP78 mRNA expression was measured by RT-PCR, and the cell
apoptosis was evaluated by TUNEL staining. Results Compared with those in group A, GRP78 mRNA and protein
expressions of GRP78, CHOP, caspase-12 related with ERS increased significantly in groups C and D (P<0.05), especially in
group D (P<0.05), but not in group B (P>0.05). Apoptotic cells and Bax expression increased and Bcl-2 expression decreased
significantly in groups C and D (P<0.05), but not in group B (P>0.05); such changes were more prominent in group D than in
group C (P<0.05). Conclusion Mild controlled hypotension (70 mmHg) does not induce neuronal injury in rat cerebral cortex,
but severe hypertension (lower than 50 mmHg) can cause neuronal ERS and apoptosis.