摘要
目的探讨参附注射液对新生大鼠缺氧缺血性脑损伤（hypoxic—ischemic brain damage，HIBD）后脑皮质神经元内质网应激相关因子氧调节蛋白150（oxygen regulate protein 150，ORP150）、X盒结合蛋白1（X—box binding protein 1，XBP1）和C／EBP同源蛋白（C／EBP homologous protein，CHOP）mRNA表达的影响。方法新生7d的Sprague—Dawley大鼠随机分为假手术组、生理盐水对照组与参附治疗组（参附注射液，10ml／kg，腹腔注射，1次／d，连续3d）。按照造模后不同观察时间点又分为3h、6h、12h、24h、3d、7d6个亚组，每个亚组8只。建立新生大鼠HIBD模型。采用逆转录聚合酶链反应检测大鼠大脑皮质ORP150、XBP1和CHOP mRNA表达。结果假手术组ORP150、XBP1和CHOP基因表达很弱。生理盐水对照组和参附治疗组ORP150、XBP1和CHOP mRNA表达在模型制作后3h即较假手术组显著性上调（P均〈0．05）；XBP1和CHOP mRNA表达分别在6h和12h时达高峰，之后均有所下降，7d时接近假手术组水平。其中，参附治疗组XBP1和CHOP mRNA表达在模型制作后12h、24h和3d时显著性低于生理盐水对照组（P均〈0．05）；生理盐水对照组XBP1 mRNA表达与CHOP mRNA表达呈显著正相关（r=0．649，P〈0．05）。结论新生大鼠HIBD可诱发内质网应激反应，ORP150、XBP1和CHOP可能参与了新生大鼠HIBD后迟发性神经元损伤过程。参附注射液可下调XBP1和CHOP mRNA表达，抑制内质网应激反应。
Objective To investigate the effect of Shenfu injection on the expressions of endoplasmic reticulum stress-related factors oxygen-regulated protein 150 （ORP150）, X-box binding protein 1 （XBP1）, and C/EBP homologous protein （CHOP） mRNAs in cerebral cortical neurons after hypoxic-ischemic brain damage （HIBD） in neonatal rats. Methods The 7 day-newborn Sprague-Dawley rats were randomly divided into sham operation, normal saline and Shenfu treatment （Shenfu injection, 10 ml/kg per day, peritoneal injection, for 3 days） groups. They were redivided into 3 h, 6 h, 12 h, 24 h, 3 d and 7 d subgroups at different time points after modeling （n = 8 in each group）. A HIBD model of the neonatal rats was induced. Reverse transcription-polymerase chain reaction was used to detect the expressions of ORP150, XBP1, and CHOP mRNAs in rat cerebral cortex. Results The expressions of ORP150, XBP1 and CHOP mRNAs of the sham operation group was very week. The expressions of ORP150, XBP1 and CHOP mRNAs in the normal saline group and the Shenfu treatment group were significantly upregulated compared to those in the sham operation group at 3 h after modeling （all P 〈 0. 05）; the expressions of XBP1 and CHOP mRNAs reached the peak at 6 and 12 h, respectively. Then they decreased mildly and closed to the level in the sham operation group at day 7. The expressions of XBP1 and CHOP mRNAs in the Shenfu treatment group at 12, 24 h and day 3 after modeling were significantly lower than those in the normal saline group （all P 〈0. 05）. The XBP1 mRNA expression was significantly positively correlated with the CHOP mRNA expression in the normal saline group （r =0. 649, P 〈0. 05）. Conclusions HIBD in neonatal rats induces endoplasmic reticulum stress response. ORP150, XBP1 and CHOP may be involved in the delayed neuronal damage process after HIBD in neonatal rats. Shenfu injection downregulates the expression of XBP1 and CHOP mRNAs and inhibits endoplasmic reticuhma stress response.
出处
《国际脑血管病杂志》
北大核心
2014年第9期665-670,共6页
International Journal of Cerebrovascular Diseases
基金
江苏省高校自然科学基础研究计划项目（08KJB320019）
关键词
缺氧缺血
脑
氧调节蛋白
转录因子CHOP
调节因子X转录因子
基因表达
内质网
参附注射液
大鼠
Hypoxia-Ischemia, Brain
Regulatory Factor X Transcription Factors
Transcription Factor CHOP
Oxygen-Regulated Proteins
Gene Expression
Endoplasmic Reticulum
Shen Fu Zhu She Ye
Rats
