Abstract
Objective To evaluate the effect of ulinastatin on programmed necrosis in hippocampal neurons in a rat model of global cerebral ischemia-reperfusion (I/R). Methods Forty-eight clean-grade healthy adult male Sprague-Dawley rats, aged 8 weeks, weighing 280-320 g, were divided into 3 groups(n=16 each)using a random number table method: sham operation group(Sham group), global cerebral I/R group(I/R group)and ulinastatin group(UT group). Global cerebral I/R was produced by 4-vessel occlusion method in chloral hydrate-anesthetized rats in I/R and UT groups. Ulinastatin 100 000 U/kg was injected via the tail vein at the onset of ischemia in group UT, and the equal volume of normal saline was given instead in Sham and I/R groups.Neurological deficit score(NDS)was estimated at 6, 12 and 24 h of reperfusion.Animals were sacrificed at 24 h of reperfusion, brains were removed and the hippocampi were obtained for examination of pathological changes (with a light microscope) and for determination of the malondialdehyde (MDA) content and superoxide dismutase (SOD) activity (by spectrophotometry), and expression of receptor-interacting protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like protein (MLKL) in hippocampal tissues (by Western blot). Results Compared with Sham group, the NDS was significantly increased at each time point, the MDA content was increased, the SOD activity was decreased, and the expression of RIPK1, RIPK3 and MLKL was up-regulated in I/R and UT groups (P<0.05). Compared with I/R group, the NDS was significantly decreased at each time point, the MDA content was decreased, the SOD activity was increased, and the expression of RIPK1, RIPK3 and MLKL was down-regulated in UT group (P<0.05). The pathological changes of hippocampi were significantly attenuated in UT group when compared with I/R group. Conclusion The mechanism by which ulinastatin ameliorates global cerebral I/R injury is related to inhibiting programmed necrosis in hippocampal neurons of rats. Key words: Trypsin inhibitors; Reperfusion injury; Hippocampus; Neurons; Necrosis
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.