CAJ | 학술논문

目的探讨脂氧素A4对大鼠局灶性脑缺血再灌注损伤时炎性反应的影响.方法雄性健康SD大鼠56只,体重200～250 g,随机分为3组:假手术组(S组,n=8),缺血再灌注组(I/R组,n=24),脂氧素A4组(LXA4组,n=24).采用线栓法阻塞大鼠右侧大脑中动脉制备局灶性脑缺血再灌注模型,LXA4组脑缺血后5 min经侧脑室注射脂氧素A4 0.03 nmol/5 μl,S组和I/R组注射等容量生理盐水,缺血2 h后拔出线栓行再灌注.再灌注24 h时行神经功能缺陷评分,然后断头取脑,光镜下观察病理学,采用比色法检测髓过氧化物酶活性,免疫组织化学方法检测星形胶质细胞和小胶质细胞的活化,ELISA法检测再灌注1、6、12、24和48 h时TNF-α、IL-β、转化生长因子β(TGF-β1)及IL-10的含量.结果与S组比较,I/R组大鼠神经功能缺陷评分、髓过氧化物酶活性、TNF-α、IL-1β、TGF-β1和IL-10的含量升高,星形胶质细胞和小胶质细胞的活化数目增多(P<0.05);与I/R组比较,LXA4组神经功能缺陷评分、髓过氧化物酶活性、TNF-α和IL-1β含量降低,TGF-β1,和IL-10含量升高,星形胶质细胞和小胶质细胞的活化数目减少(P<0.05).病理结果显示:LXA4组脑缺血再灌注损伤程度较I/R组减轻.结论脂氧素A4可通过抑制炎性反应减轻大鼠局灶性脑缺血再灌注损伤.
목적 탐토지양소A4대대서국조성뇌결혈재관주손상시염성반응적영향.방법 웅성건강SD대서56지,체중200～250 g,수궤분위3조:가수술조(S조,n=8),결혈재관주조(I/R조,n=24),지양소A4조(LXA4조,n=24).채용선전법조새대서우측대뇌중동맥제비국조성뇌결혈재관주모형,LXA4조뇌결혈후5 min경측뇌실주사지양소A4 0.03 nmol/5 μl,S조화I/R조주사등용량생리염수,결혈2 h후발출선전행재관주.재관주24 h시행신경공능결함평분,연후단두취뇌,광경하관찰병이학,채용비색법검측수과양화물매활성,면역조직화학방법검측성형효질세포화소효질세포적활화,ELISA법검측재관주1、6、12、24화48 h시TNF-α、IL-β、전화생장인자β(TGF-β1)급IL-10적함량.결과 여S조비교,I/R조대서신경공능결함평분、수과양화물매활성、TNF-α、IL-1β、TGF-β1화IL-10적함량승고,성형효질세포화소효질세포적활화수목증다(P<0.05);여I/R조비교,LXA4조신경공능결함평분、수과양화물매활성、TNF-α화IL-1β함량강저,TGF-β1,화IL-10함량승고,성형효질세포화소효질세포적활화수목감소(P<0.05).병리결과현시:LXA4조뇌결혈재관주손상정도교I/R조감경.결론 지양소A4가통과억제염성반응감경대서국조성뇌결혈재관주손상.
Objective To investigate the effects of lipoxin A4 (LXA4) on the inflammatory response to focal cerebral ischemia-reperfusion(I/R) inmy in rats.Methods Fifty-six healthy male SD rats weighing 200-250 g were randomly divided into 3 groups:group Ⅰ sham operation(group S,n=8);group Ⅱ cerebral I/R(n=24)and group Ⅲ lipoxin A4+I/R(group LXA4,n=24).Right mid-cerebral artery was occluded for 2 h by inserting cranially a nylon thread with rounded tip into internal carotid artery.LXA4 0.03 nmol/5 μl was injected into cerebral ventricle at 5 min after cerebral ischemia.Neurological deficit was scored at 24 h of reperfusion.Then four animals in each group were killed and their brains were removed for microscopic examination and expression of MPO at 24 h of reperfusion.Meantime,content of IL-1β,TNF-α,TGF-β1,and IL-10 in the brain tissue were measured at 1,6,12,24 and 48 h of reperfusion by ELISA.Glial cell activity was examined at 24 h of reperfusion by immuno-histochemistry.Results Intra-cerebroventricular administrated LXA4 0.03 nmol/5 μl provided mild neuroprotection against focal cerebral I/R injury,improved neurological deficits,and reduced morphological brain damages and PMN infiltration.LXA4 also decreased the content of TNF-α and IL-1β,and increased the content of IL-10 and TGF-β1.The numbers of activated astroglia and microglia were decreased in group LXA4 compared with group I/R.Conclusion LXA4 protects the brain against I/R injury by inhibiting inflammatory response.