科研之友
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摘要
Background: The effects of Ulinastatin (UTI) on the blood-brain barrier (BBB) in the acute phase of cerebral ischemia/reperfusion (I/R) are not clear. This study was to investigate the potential protective effects of UTI on the BBB and the underlying mechanisms.& para;Methods: Male CD-1 mice were subjected to transient middle cerebral artery occlusion (tMCAO) and randomly assigned to four groups: Sham (sham-operated), tMCAO (tMCAO + 0.9% saline), UTI-L (tMCAO + UTI 1500 U/100 g) and UTI-H (tMCAO + UTI 3000 U/100 g) group. UTI was administered immediately after reperfusion in the UTI-L and UTI-H groups. At 24 h after reperfusion, the neurological deficit, brain water content, and infarct volume were determined. Western blot and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to examine the expression of matrix metalloproteinase (MMP)-9, Zonula occludens-1 (ZO-1) and occludin in ischemic cerebral cortex. The integrity of the BBB was assessed by the leakage of Evans blue. & para;& para;Results: Compared with tMCAO group, both UTI-L and UTI-H groups showed significantly (P < 0.001) ameliorated the neurological deficit (2.00 +/- 0.71 and 1.60 +/- 0.55 vs. 4.60 +/- 0.55), lessened brain water content (82.99% +/- 0.21% and 82.05% +/- 0.59% vs. 84.28% +/- 0.0.57%) and decreased the infarct volume (38.52% +/- 1.72% and 24.78% +/- 1.20% vs. 49.48% +/- 1.93%). In addition, significantly (P < 0.001) decreased expression of MMP-9 (0.48 0.06 and 0.37 +/- 0.05 vs.0.76 +/- 0.10 for protein and 2.88 +/- 0.23 and 2.17 +/- 0.16 vs. 3.90 +/- 0.24 for mRNA) and alleviated loss of ZO-1 (0.19 +/- 0.04 and 0.24 0.05 vs. 0.25 +/- 0.03) and occludin (0.74 +/- 0.08 and 0.87 +/- 0.07 vs. 0.94 +/- 0.06) proteins were observed in both UTI-L and UTI-H groups.& para;& para;Conclusion: UTI protects the brain against ischemic injury potentially via down-regulating the expression of MMP-9 and alleviating loss of ZO-1 and occludin proteins to restore the BBB permeability.
