Rats In Ischemia-reperfusion Group Research Articles

Influences of miR-708 on cerebral ischemia-reperfusion injury through targeted regulation of ADAM17.

The purpose of this study was to explore the influences of micro ribonucleic acid (miR)-708 on cerebral ischemia-reperfusion injury by regulating a disintegrin and metalloprotease 17 (ADAM17) in a targeted manner. The rat model of middle cerebral artery occlusion (MCAO) was established, and the differentially expressed miRNAs in the cerebral tissues of rats with ischemia-reperfusion injury were detected via sequencing. The research was performed in control group (PC12 cells received no treatment), inhibitor group (the expression of miR-708 in PC12 cells was down-regulated using miR-708 inhibitor), and interference + inhibitor group [PC12 cells were co-treated with miR-708 inhibitor and ADAM17 small interfering RNA (siRNA)]. Then, the expression of ADAM17 in cells, proliferation ability of cells, and number of apoptotic cells were detected in each group. A total of 225 differentially expressed miRNAs were obtained through miRNA sequencing and bioinformatics analysis, of which miR-708, miR-169, miR-26, and miR-96 were highly expressed, whereas miR-122, miR-118, and miR-177 were lowly expressed in rats in ischemia-reperfusion group. Compared with that in control group, the level of miR-708 declined significantly in inhibitor group after treatment with miR-708 inhibitor. After treatment with miR-708 inhibitor, the protein expression level of ADAM17 in inhibitor group was evidently higher than that in control group, while its protein expression level in interference + inhibitor group was significantly decreased and restored, after interference of ADAM17 siRNA with protein expression. In comparison with control group, inhibitor group had increased apoptotic cells after miR-708 inhibitor treatment (p<0.05). Besides, after interference of ADAM17 siRNA with protein expression, there were a smaller number of apoptotic cells in interference + inhibitor group (p<0.05), showing mitigated apoptosis. Moreover, the proliferation ability of cells treated with miR-708 inhibitor in inhibitor group was weaker than that in control group (p<0.05), whereas the proliferation ability of cells in interference + inhibitor group was restored to a certain degree after ADAM17 siRNA interfered with the protein expression (p<0.05). MiR-708 can modulate ADAM17 in a targeted manner to affect cellular proliferation and apoptosis in cerebral ischemia-reperfusion injury.

Edaravone enhances the viability of ischemia/reperfusion flaps.

The purpose of the experiment was to study the efficacy of edaravone in enhancing flap viability after ischemia/reperfusion (IR) and its mechanism. Forty-eight adult male SD rats were randomly divided into 3 groups: control group (n=16), IR group (n=16), and edaravone-treated IR group (n=16). An island flap at left lower abdomen (6.0 cm×3.0 cm in size), fed by the superficial epigastric artery and vein, was created in each rat of all the three groups. The arterial blood flow of flaps in IR group and edaravone-treated IR group was blocked for 10 h, and then the blood perfusion was restored. From 15 min before reperfusion, rats in the edaravone-treated IR group were intraperitoneally injected with edaravone (10 mg/kg), once every 12 h, for 3 days. Rats in the IR group and control group were intraperitoneally injected with saline, with the same method and frequency as the rats in the edaravone-treated IR group. In IR group and edaravone-treated IR group, samples of flaps were harvested after reperfusion of the flaps for 24 h. In the control group, samples of flaps were harvested 34 h after creation of the flaps. The content of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) were determined, and changes in organizational structure and infiltration of inflammatory cells were observed by hematoxylin-eosin (HE) staining, apoptotic cells of vascular wall were marked by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay, and the apoptotic rate of cells in vascular wall was calculated. The ultrastructural changes of vascular endothelial cells were observed by transmission electron microscopy (TEM). Seven days after the operation, we calculated the flap viability of each group, and marked vessels of flaps by immunohistochemical staining for calculating the average number of subcutaneous vessels. The results showed that the content of MDA, the number of multicore inflammatory cells and apoptotic rate of cells in vascular wall in the edaravone-treated IR group were significantly lower than those in the IR group. The activity of SOD, flap viability and average number of subcutaneous vessels in the edaravone-treated IR group were significantly higher than those in the IR group. All the differences were statistically significant. The ultrastructure injury of vascular endothelial cells in the edaravone-treated IR group was slighter than that in IR group. It was concluded that edaravone can significantly enhance IR flap viability and protect flap vessels, which is related to scavenging oxygen free radicals, reducing the consumption of SOD, reducing the extent of lipid peroxidation and inflammation, and protecting functional structure of vessels in the early stages of reperfusion.

The neuroprotection of cinepazide maleate on acute cerebral ischemic brain in rats: a proton magnetic spectroscopy study

Objective To dynamically monitor the effect of Cinepazide maleate (CM) on ischemic region of the brain and to elucidate the neuroprotection of CM on acute cerebral ischemic rat model and related mechanisms. Methods The rat model of acute brain ischemia-reperfusion was established with tighting threads. They were randomly divided into ischemia-reperfusion group and CM treatment group(n=8 in each group). Rats in CM treatment group were given 3 mg / kg CM by caudal intravenous injection immediately after brain ischemia-reperfusion. T2 weighted imaging(T2WI) and proton magnetic resonance spectroscopy (1HMRS) were performed before operation and at 6 hours, 24 hours and 3 days after reperfusion. Results At 6 h, 24 h and 3 d after operation there was no difference for areas of cerebral ischemia on T2WI between 2 groups. The values of N-acetylaspartate(NAA) (Phosphocreatine(PCr) + Creartine(Cr)) in ischemia-reperfusion group rats were (1.53±0.20), (0.50 ±0.17), (0.44±0.13), (0.40±0.10) before operation and at 6 h, 24 h, 3 d after operation, respectively. And in CM treatment group the values of NAA /(PCr+ Cr) were (1.44±0.22), (0.68±0.13), (0.61±0.10), (0.53±0.09) at the same time points. The values of lactate(Lac)/(PCr+ Cr) in ischemia-reperfusion group were (0.03±0.01), (1.10±0.28), (1.30±0.23), (1.23±0.19) before operation and at 6 h, 24 h, 3 d after operation, respectively. And in CM treatment group the values of Lac/(PCr+ Cr) were (0.02±0.01), (0.85±0.25), (0.99±0.20), (0.90±0.15 )at the same time points. The rats in ischemia-reperfusion group had lower value of NAA/(PCr+ Cr)(P<0.01) and higher value of Lac/(PCr+ Cr) at all time points after operation than those before operation. Compared with rats in ischemia-reperfusion group, the value of NAA/(PCr+ Cr) increased(P<0.05) and the value of Lac/(PCr+ Cr) decreased(P<0.05)decreased significantly for CM treatment group rats. Conclusion CM treatment can decrease the intracellular accumulation of lactic acid and reduce neuronal necrosis in acute brain ischemia-reperfusion rats. Key words: Magnetic resonance spectroscopy; Cinepazide maleate; Cerebral ischemia

Protective effect of Naoshuning in a rat brain ischemia-reperfusion damage model

To evaluate the protective effects of Naoshuning Chinese traditional medicine on the brain ischemia-reperfusion (IR) injury in rats and explore the possible mechanism of IR injury, rats were divided into 4 groups: sham-operation group, model group as negative control group, Naoshuning group as treatment group and ginaton group as positive control group. The brain IR model was established in rats. Reperfusion was carried out 2 h after ischemia. Neurological evaluation was assessed by scores when the rats came around. Brain infarct volume, superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in serum were examined, respectively at 1st day, 7th day and 14th day after reperfusion. Behavioral abnormities could be seen after the surgery. Compared with sham-operation group, the general scores was much higher in the IR group but was significantly lower in Naoshuning group and ginaton group (p<0.01). After surgery, rats in IR groups appeared much more infarcts than those in sham-operation group (P<0.01). The infarct volume in the Naoshuning group and ginaton group was markedly decreased and the decrease was more obvious at the 7th day after reperfusion (taking drug for 10 days) (P<0.01). When compared with sham group, the activity of SOD in IR group dramatically decreased and the MDA content increased significantly after injury (p<0.01). Within IR groups, the SOD activity at the 3rd and 7th day after reperfusion (taking drug for 6 and 10 days, respectively) was markedly increased in Naoshuning and ginaton group, and the MDA content was decreased significantly in Naoshuning and ginaton groups compared with sham-operation group. In conclusion, Naoshuning treatment significantly improved the neurological functions, reduced the infarct volume, decreased the MDA content and improved the SOD activity in rats undergoing IR injury, which suggests that Naoshuning can exert neuroprotective effects via inhibiting free radical generation and improving the activity of antioxidant enzymes. Key words: Naoshuning, ischemic encephalopathy, reperfusion damage, superoxide dismutase, malondialdehyde.

Effects of naoshuning on the plasma TNF-α, IL-1β and ICAM-1 levels in a rat brain ischemia-reperfusion injury model

To investigate the effects of naoshuning on plasma TNF-α, IL-1β and ICAM-1 levels in a rat brain ischemia-reperfusion injury model. 72 rats were randomly divided into four groups (n=18): Sham group, ischemia-reperfusion (IR) group, naoshuning group and ginaton group. Middle cerebral artery occlusion (MCAO) was performed in rats for 2 h followed by 1, 7 and 14 days of reperfusion. Animals were sacrificed and the plasma levels of TNF-α, IL-1β and ICAM-1 were detected by ELISA and radioimmunoassay. After brain ischemia-reperfusion injury, the contents of TNF-α, IL-1β and ICAM-1 in the plasma of rats in IR group were significantly higher than that in sham group (p<0.05); after the treatment with naoshuning, the contents of TNF-α, IL-1β and ICAM-1 in the plasma was significantly decreased when compared with those in the remaining groups (P<0.05). When compared with the MCAO group, the TNF-α, IL-1β and ICAM-1 levels in naoshuning group was decreased after injury (P<0.05). Naoshuning can decrease the secretion of inflammatory cytokines (TNF-α, IL-1β) and adhesion molecules (ICAM-1), improving brain ischemia reperfusion injury. Key words: Naoshuning, brain ischemia reperfusion, tumor necrosis factor-α, interleukin-1β, intercellular adhersion molecule-1.