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. 2012 Nov 5;7(31):2432-8.
doi: 10.3969/j.issn.1673-5374.2012.31.004.

Silencing the gene encoding C/EBP homologous protein lessens acute brain injury following ischemia/reperfusion

Fengzhang Wang  1 , Yuan Zhang  2 , Chunke He  3 , Tingting Wang  4 , Qiyan Piao  5 , Qun Liu  1
Affiliations

Silencing the gene encoding C/EBP homologous protein lessens acute brain injury following ischemia/reperfusion

Fengzhang Wang et al. Neural Regen Res. .

Abstract

C/EBP homologous protein, an important transcription factor during endoplasmic reticulum stress, participates in cell apoptosis mediated by endoplasmic reticulum stress. Previous studies have shown that C/EBP homologous protein mediates nerve injury during Alzheimer's disease, subarachnoid hemorrhage and spinal cord trauma. In this study, we introduced C/EBP homologous protein short hairpin RNA into the brains of ischemia/reperfusion rat models via injection of lentiviral vector through the left lateral ventricle. Silencing C/EBP homologous protein gene expression significantly reduced cerebral infarction volume, decreased water content and tumor necrosis factor-α and interleukin-1β mRNA expression in brain tissues following infarction, diminished the number of TUNEL-positive cells in the infarct region, decreased caspase-3 protein content and increased Bcl-2 protein content. These results suggest that silencing C/EBP homologous protein lessens cell apoptosis and inflammatory reactions, thereby protecting nerves.

Keywords: Alzheimer’s disease; C/EBP homologous protein; cerebral infarction; endoplasmic reticulum stress; interleukin-1β; ischemia/reperfusion; neural regeneration; subarachnoid hemorrhage; tumor necrosis factor-α.

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Conflict of interest statement

Conflicts of interest: None declared.

Figures

Figure 1
Figure 1
Infarct volume in rats from the control, vector and lentiviral vector (LV)-short hairpin RNA (shRNA) groups (2,3,5-triphenyltetrazolium chloride staining). There was an obvious, large, gray infarct region, which involved the cortex, hippocampus and basal ganglia in each group following model induction using the suture occlusion method. Volume in the LV-shRNA group: aP < 0.01, vs. control and vector groups. Mean ± SD, n = 3, one-way analysis of variance and Student-Newman-Keuls test.
Figure 2
Figure 2
C/EBP homologous protein gene silencing effects tumor necrosis factor-α (TNF-α) mRNA (A) and interleukin-1β (IL-1β) mRNA (B) expression in the infarct region of rats following ischemia/reperfusion. Results are expressed as the ratio of the absorbance values of TNF-α and IL-1β mRNA to that of the house-keeping gene GAPDH. aP < 0.01, vs. control and vector groups. Mean ± SD, n = 6, one-way analysis of variance and Student-Newman-Keuls test.
Figure 3
Figure 3
Effects of C/EBP homologous protein (CHOP) gene silencing on Bcl-2 and caspase-3 protein expression in the cerebral infarct regions of rats following ischemia/reperfusion. Results are expressed as the ratio of the absorbance values of target protein to the house-keeping protein GAPDH. Expression levels in the lentiviral vector (LV)-short hairpin RNA (shRNA) group: aP < 0.05, vs. control and vector groups. Mean ± SD, n = 6, one-way analysis of variance and Student-Newman-Keuls test.
Figure 4
Figure 4
Effects of C/EBP homologous protein gene silencing on cell apoptosis in the rat cerebral infarct region following ischemia/reperfusion. Cell apopotsis in control group, vector group and lentiviral vector (LV)-short hairpin RNA (shRNA) group, respectively (A–C; TUNEL staining, × 200) there were round or elliptic apoptotic cells showing pyknosis and karyorrhexis. (D) Quantification of TUNEL-positive cells. aP < 0.05, vs. control and vector groups. Mean ± SD, n = 3, one-way analysis of variance and Student-Newman-Keuls test.
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