ABSTRACT
Objective To investigate the effects of edaravone (EDA) on cell apoptosis induced by endoplasmic reticu?lum stress (ESR) after spinal cord injury (SCI) in rats. Methods Thirty-six healthy adult SD rats were randomly divided in?to three groups (12 rats for each group):Sham group, SCI group and EDA group. The rat model of SCI was made by Allen’s method and the sham group was only received laminectomy and kept the spinal cord intact. Rats in sham group and SCI group accepted the same volume and frequency of saline injection as EDA group. The EDA group was given 10 mg/kg EDA once every 12 h intraperitoneally. Three days after injuring, the spinal cords were harvested, and the protein levels of C/EBP homologous protein (CHOP), Cleaved caspase-12 and Cleaved caspase-3 were detected by Western blot assay. Immunofluo?rescence staining was used to analyze the positive ratio of caspase-12 and CHOP in spinal cord of three groups. Meanwhile, TUNEL staining was used to identify cell apoptosis of spinal cord. Results Compared with sham group, the protein levels of CHOP, Cleaved caspase-12 and Cleaved caspase-3 were obviously higher in SCI group (P<0.01);the proportion of Cas?pase-12 and CHOP positive cells was significantly increased (P<0.01), and the apoptotic rates were also significantly in?creased in spinal cord (P<0.01). However, compared with SCI group, the protein levels of CHOP , Cleaved caspase-12 and Cleaved caspase-3 were significantly decreased in EDA group (P<0.01);the proportion of Caspase-12 and CHOP positive cells was significantly reduced (P<0.01), and the apoptotic rates were also significantly decreased in spinal cord (P<0.01). Conclusion EDA has neuroprotective potential to spinal cord injury. The mechanism of its neuroprotective effect may asso?ciate with its inhibitory effect to the cell apoptosis induced by endoplasmic reticulum stress after SCI.
ABSTRACT
Objective To investigate the effects of hydrogen sulfide on autophagy and the apoptosis after acute spinal cord injury in rats. Methods Thirty-six adult male SD rats (250-300 g) were randomly divided into three groups (n=12 for each group):sham operation group (Sham group), spinal cord injury group (Model group) and hydrogen sulfide pre-treatment group (H2S group). Allen’s method was used to establish the rat model of spinal cord injury. Rats of sham operation group re?ceived only laminectomy. Rats of H2S group received sodium hydrosulphide injection intraperitoneally (50μmol/kg) 1h after spinal cord injury, and Model group was given the same amount of saline solution. Rats in the three groups were sacrificed 24 h after spinal cord injury, then the spinal cord was removed. The expressions of LC3, p70S6K and Cleaved caspase-3 were detected by Western blot assay. The expression of LC3 was also detected by immunofluorescence. The cell apoptosis was as?sessed by TUNEL stain. Results Compared with Sham group, the expression levels of LC3Ⅱ/LC3Ⅰand Cleaved caspase-3 were increased in Model group, but the expression of p70S6K decreased and cell apoptosis increased in Model group (P<0.01). Compared with Model group, the expression levels of LC3Ⅱ/LC3Ⅰand Cleaved caspase-3 were decreased significant?ly, while the expression of p70S6K increased and cell apoptosis decreased significantly in H2S group (P < 0.01). Conclu?sion Hydrogen sulfide can inhibit autophagy and reduce cell apoptosis after acute spinal cord injury in rats.
ABSTRACT
Objective To study the effect of Exendin-4 on oxidative stress and neural apoptosis following spinal cord injury (SCI). Methods Adult male SD rats, with weight between 200-250 g, were randomly divided into three groups (12 in each group):Sham group, SCI group and Exendin-4 group (Ex-4 group). Rats in Sham group achieved spinal cord exposure. SCI group and Ex-4 group were induced according to Allen′s test (using a weight-drop device). Rats in Ex-4 group were ad?ministrated with Exendin-4 (10 μg/rat) through intraperitoneal injection immediately after establishment of SCI models. Rats in Sham group and SCI group were given the same volume of normal saline solution instead. Level of malondialdehyde (MDA) and the activity of catalase (CAT) were assessed in spinal cord tissues 24 hour after drug administrations. Neural apoptosis was detected by TUNEL staining and the expression levels of caspase-9 and AIF were determined using Western blot. Results Compared with Sham group, the levels of MDA, caspase-9 and AIF as well as neuronal apoptosis rate in?creased obviously, while activity of CAT decreased markedly in SCI group(P<0.01). Compared with SCI group, the levels of MDA, caspase-9 and AIF as well as the neuronal apoptosis rate decreased obviously, while activity of CAT increased re?markably in Exendin-4 group(P < 0.01). Conclusion Exendin-4 restrain neural apoptosis following spinal cord injury through relieving oxidative damage.