ABSTRACT
Objective To evaluate the effect of inhibition of ubiquitin carboxy terminal hydrolase LI (UCHL1) on cerebral ischemia/reperfusion injury in mice. Methods Male BALB/c mice were randomly divided into sham group, ischemia/reperfusion (I/R) group, UCHL1 small interfering RNA (siRNA)group and scramble siRNA (control) group, 10 mice in each group. I/R model was established by reperfusion 24 hours after middle cerebral artery occlusion (MCAO) 60 minutes. In the siRNA group and control group, 10 JJLI UCHL1 siRNA or scramble siRNA was injected into the brain through the lateral ventricle 24 hours before MCAO. The expression of UCHL1 was detected by RT-PCR and Western blotting; the volume of cerebral infarction and the rate of edema were assessed by 2, 3, 5-triphenyl tetrazolium chloride (TTC) staining; and the score of neurological symptoms was assessed by neurobehavioral scoring. Results Compared with the sham group, the level of UCHL1 mRNA and protein in ischemic penumbra of I/R group were significantly higher (P< 0.05), while the expression of UCHL1 protein and mRNA in siRNA group were significantly lower (P< 0.05); at the same time, the volume of cerebral infarction, edema rate and neurobehavioral damage in I/R group increased significantly, while the volume and edema rate of cerebral infarction and neurobehavioral damage in siRNA group further increased (P< 0.05). Conclusion Inhibition of UCHL1 can aggravate the cerebral ischemia/reperfusion injury in mice, suggesting that the induction of UCHL1 after MCAO has a protective effect on the cerebral ischemia/reperfusion injury in mice.
ABSTRACT
Objective To investigate the effects of transient receptor potential vanilloid-1 (TRPV1) antagonist AMG517 on cerebral ischemic / reperfusion injury in mice. Methods Forty male C57BL / 6 mice were assigned to the following groups: sham group, vehicle + ischemia / reperfusion group (vehicle), capsaicin + ischemia / reperfusion group (capsaicin), and AMG517 + ischemia / reperfusion group (AMG517) . Ischemic / reperfusion injury was induced by permanent middle cerebral artery occlusion(MCAO) and neurological deficits were evaluated 72 hours after MCAO. Then, infarct volume, brain edema, mRNA expression of TRPV1 and serum concentrations of tumor necrosis factor α(TNF-α) and interleukin-10 (IL-10) were measured. Results Compared with the vehicle group, AMG517 significantly decreased the infarct volume (P < 0. 01) . Neurobehavioral score significantly decreased following administration of AMG517 (P < 0. 01) 72 hours after MCAO. Compared with the sham group, the mRNA expression of TRPV1 significantly increased in vehicle group (P < 0. 01) . AMG517 significantly increased the anti-inflammatory cytokine IL-10 and decreased the inflammatory cytokine TNF-α (P<0. 05) . Conclusion AMG517 can improve ischemia / reperfusion injury in mice and may play a neuroprotective effect by alleviating inflammation.