Effect of Shen fu injection on the expressions of ORP150, XBP1 and CHOP mRNAs in hypoxic-ischemic neonatal rats

Abstract

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, 10ml/kg per day, peritoneal injection, for 3 days) groups. They were redivided into 3h, 6h, 12h, 24h, 3d and 7d subgroups at different time pointsafter modeling(n=8 in each group). A HIBD model of the neonatal rats was induced. Reverse transcriptionpolymerase 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 3h after modeling (all P< 0.05); the expressions of XBP1 and CHOP mRNAs reached the peak at 6 and 12h, 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, 24h 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 reticulum stress response. Key words: Hypoxia-Ischemia, Brain; Regulatory Factor X Transcription Factors; Transcription Factor CHOP; Oxygen-Regulated Proteins; Gene Expression; Endoplasmic Reticulum; Shen Fu Zhu She Ye; Rats