Effect of tumor necrosis factor alpha treatment on cerebral ischemia-reperfusion injury in rats
- VernacularTitle:注射肿瘤坏死因子-α对大鼠脑缺血再灌注的影响
- Author:
Qingcheng LIANG
;
Yun WU
;
Shujie SHI
;
Haiyan Lü
- Publication Type:Journal Article
- From:
Chinese Journal of Tissue Engineering Research
2005;9(41):168-171
- CountryChina
- Language:Chinese
-
Abstract:
BACKGROUND: Some studies suggest that pre-injection of tumor necrosis factor-α (TNF-α)can protect focal cerebral ischemia in mice. Cerebral ischemia tolerance is related to the increase of TNF-α level; on the other hand, TNF-α is an injurious cytokine associated with stroke. Circulating antibody against anti-TNF-α can protect reperfused injury.OBJECTIVE: To study the effects of TNF-α pretreatment and post-treatment on cerebral ischemia-reperfusion injury and explore possible mechanism.DESIGN: Randomized controlled study.SETTING: Neurological Department, the Second Hospital Affiliated to Harbin Medical University.MATERIALS: The experiment was conducted at the Animal Experiment Center of Harbin Medical University from January to April 2002. Totally 120 healthy adult male Wistar rats were randomly divided into the following 8 groups: TNF-α 0.05 μg, 0.5 μg and 1.0 μg pretreatment groups and PBS group, TNF-α 0.05 μg, 0.5 μg and 1.0 μg post-treatment groups and PBS group with 15 in each group.METHODS: The focal brain ischemia model of middle cerebral artery occlusion (MCAO) was made using inserting thread method. TNF-α of different doses (0.05 μg, 0.5 μg or 1.0 μg) or PBS was injected intracisternally and 22-hour reperfusion, 8 rats from each group were killed. Then the perhour reperfusion, 7 rats from each group were killed. Then pathological changes were observed, glial fibrillary acidic protein (GFAP) and intercellular adhesion molecule-1 (ICAM-1) expression were inspected by immunohistochemical method. Histopathological and immunohistochemical evaluation was made with the computer-assisted image analyzing system,and the number of GFAP positive cells and ICAM-1 positive vessels in each hemisphere was counted.riliary acidic protein and ICAM-1.infarct volume: TNF-α 0.5 μg and TNF-α 1.0 μg pretreatment groups showed reduced volume of lesion; infarct volume reduced by 70.9% in TNF-α 0.5 μg pretreatment rats and 66.5% in TNF-α 1.0 μg pretreatment rats. TNF-α 0.5 μg and TNF-α 1.0 μg post-treatment groups showed increased volume of lesion; infarct volume increased by 22.3% in TNF-α 0.5 μg post-treatment rats and 46.7% in TNF-α 1.0 μg post-treatment rats.TNF-α 0.05 μg and 1.0 μg pretreatment groups did not differ significantly (P ＞ 0.05), but there was an obvious difference between TNF-α 0.5 μg and pared with PBS pretreatment group, TNF-α 0.5 μg and 1.0 μg pretreatment groups showed lessened tissue damage and edema. Compared with PBS post-treatment group, TNF-α 0.5 μg and TNF-α 1.0 μg post-treatment fibriliary acidic protein and ICAM-1: TNF-α 0.5 μg and TNF-α 1.0 μg pretreatment groups showed reduced volume of glial fibriliary acidic protein and ICAM-1 (P ＜ 0.05); but TNF-α 0.5 μg and TNF-α 1.0 μg posttreatment groups showed increased volume of glial fibriliary acidic protein and ICAM-1 (P ＜ 0.05). TNF-α 0.05 μg and 1.0 μg pretreatment groups did not differ significantly (P ＞ 0.05); but there was an obvious difference between TNF-α 0.5 μg and 1.0 μg post-treatment groups (P ＜ 0.05).cerebral ischemia reperfusion injury. This effect is not related to the repair given after cerebral ischemia reperfusion, ischemia exacerbates, which is α are determined by whether TNF-αis given before or after cerebral ischemia in a dose-dependent manner.
