Effects of hydrochloride fasudil on inflammatory response and secondary brain injury in rats after intracerebral hemorrhage
10.3760/cma.j.issn.1671-8925.2017.11.001
- VernacularTitle:盐酸法舒地尔对脑出血大鼠炎性反应及继发性脑损伤的影响研究
- Author:
Limin LI
1
;
Fangping YU
;
Li ZHANG
;
Yingchun ZHAO
;
Xiaoli LOU
;
Kunlun ZHANG
;
Ping JIANG
Author Information
1. 南京医科大学附属上海松江中心医院神经内科
- Keywords:
Intracerebral hemorrhage;
Hydrochloride fasudil;
Inflammatory response;
Brain injury
- From:
Chinese Journal of Neuromedicine
2017;16(11):1081-1090
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of hydrochloride fasudil on inflammation and secondary brain injury in rats after intracerebral hemorrhage (ICH).Methods One hundred and seventeen male Wistar rats were randomly divided into normal group (n=9),sham-operated group (n=36),ICH group (n=36) and hydrochloride fasudil treatment group (ICH/HF,n=36).ICH was caused by injecting non-anticoagulant autologous arterial blood into the right caudate nucleus,3 mg HF was dissolved in 2 mL 0.9％ saline solution and administrated intraperitioneally once daily (12 mg/kg/d) since 12 h ofICH onset.Rats in the sham-operated group and ICH group received an equal volume of normal saline.On one,3,7 and 14 d ofICH induction,Bederson method was used to score neurological deficits in rats;interleukin (IL)-6 and tumor necrosis factor (TNF)-α levels in serum were detected by enzyme-linked immunosorbent assay (ELISA).Brain edema was measured by comparing wet and dry brain weights.Inflammatory cell infiltration around the hematoma was visualized using hematoxylin and eosin,and changes in neuronal morphology were detected by Nissl staining.Immunohistochemistry method was used to detect the expressions of Caspase-3 and Bcl-2.Results (1) The neurological deficit scale scores on one and 3 d ofICH in the ICH/HF group were significantly decreased as compared with those in the ICH group (P＜0.05).(2) Serum IL-6 (except 14 d of ICH) and TNF-α levels in ICH/HF group were significantly decreased as compared with those in the ICH group (P＜0.05).(3) Brain water contents at each time point in ICH/HF group were significantly decreased as compared with those in the ICH group (P＜0.05).(4) HE staining showed the sizes of hematoma on one and 3 d ofICH in the ICH/HF group and ICH group were consistent;but ICH/HF group had smaller hematomas on 7 d of ICH,and disappeared hematoma and glial cell hyperplasia on 14 d of ICH.Mass neutrophils infiltration developed in the perihematomal areas of the ICH and ICH/HF groups;however,neutrophils infiltration in the ICH/HF group ([20.56±6.37] cells/field) was significantly decreased as compared with that in the ICH group ([41.50±8.91] cells/field) on one d of ICH (P＜0.05).(5) Nissl staining showed neuron death and loss in the perihematomal areas on one,3 and 7 d of ICH in the ICH group;but ICH/HF group had significantly increased neuron number as compared with the ICH group (P＜0.05).(6) The Caspase-3 expression on 3 and 7 d ofICH in the ICH/HF group was significantly decreased as compared with that in the ICH group (P＜0.05);the Bcl-2 expressions at each time point in the ICH/HF group was significantly increased as compared with that in the ICH group (P＜0.05).Conclusion HF exerts neuroprotective effects in ICH rat models by decreasing serum IL-6 and TNF-α levels,reducing neutrophils infiltration and neuronal necrosis around the hematoma,restraining the cell apoptosis through down-regulating Caspase-3 and up-regulating expression of Bcl-2,alleviating the brain edema,and improving the neurological outcome.
