Protective role of Mn(III)tetrakis (4-benzoic acid) porphyrin in intracerebral hemorrhage in rats and its mechanism

Abstract

Objective To explore the protective effect of Mn(III)tetrakis (4- benzoic acid) porphyrin (MnTBAP) on rats after intracerebral hemorrhage (ICH) and its mechanism. Methods Sixty- six adult SD rats were randomized into sham- operated group, control group and experimental group (n=22). Rats in the latter two groups were performed stereotactic injection of autologous tail arterial blood to induce ICH models; the rats in the experimental group were given 2 μL MnTBAP (100 μg/μL) by intracerebroventricular injection 30 min after ICH, while the rats in the control group were given normal saline of same volume. The expressions of 4-hydroxynonenonal (4-HNE, a marker of lipid peroxidation), 3- nitrotyrosine (3- NT, a reliable marker of protein nitration), 8- hydroxy- 2'- deoxyguanosine (8-OHdG, a marker of DNA oxidative damage), Zonula occludens-1 (ZO-1, a kind of tight junction protein) and myeloperoxidase (MPO, a marker of neutrophil) in the perihematomal brain tissues 24 h after ICH were detected by immunofluorescence; protein expressions of ZO- 1 and matrix metalloproteinase-9 (MMP-9) were detected by Western blotting 24 h after ICH; brain water content and modified neurological severity (mNSS) scores were measured 24 and 72 h after ICH. Results As compared with those in the control group, 3-NT (264.53±83.99vs 413.22±89.16), 4-HNE (245.64±73.10 vs 391.41±51.43), 8-OHdG (221.53±68.25vs 332.32±94.93), MPO (296.14±66.34vs 431.59±102.68) and MMP-9 (0.75±0.07vs 0.96±0.04) expressions in perihematomal brains of experimental group were significantly decreased, while the expressions of ZO- 1 (0.74 ± 0.05vs 0.56 ± 0.06) were significantly increased (P<0.05). The mNSS scores (9.33±1.37vs 11.33±1.51; 6.17±0.98vs 9.50±1.38) and brain water contents in the experimental group were significantly lower as compared with those in the control group 24 and 72 h after ICH (80.41%±0.69%vs 82.48%±0.94%; 79.78%±0.65%vs 81.57%±0.82%) (P< 0.05). Conclusion MnTBAP could protect injured brain tissues by alleviating oxidative and nitrative stress, decreasing neutrophils invasion and MMP- 9 activation at early stage of ICH; meanwhile, MnTBAP could relieve the blood-brain barrier disruption and neurological deficit following ICH. Key words: Intracerebral hemorrhage; Mn(III)tetrakis (4-benzoic acid) porphyrin; Oxidative and nitrative stress