摘要
目的:观察L-硝基精氨酸(L-NA)对局灶性脑缺血损伤后炎症因子和神经细胞凋亡的影响,探讨L-NA保护脑缺血损伤组织的作用机制。方法:健康雄性SD大鼠,体重250-280g,随机分为3组(n=10):假手术组(SH组)、缺血组(IS组)、L-NA治疗组(L-NA组)。IS、L-NA组采用线栓法制备大鼠局灶性脑缺血损伤模型。L-NA组每次腹腔注射L-NA20mg/kg,每日2次,连续3d。IS组给予等量的生理盐水。将大鼠断头取脑,采用免疫组化法检测脑组织中TNF-α表达变化,放免法检测IL-1β水平变化,流式细胞仪测定脑组织神经元凋亡率、Bcl-2蛋白、Bax蛋白表达及Bcl-2蛋白与Bax蛋白比值(Bcl-2/Bax)。结果:与SH组比较,IS组脑缺血灶范围内TNF-α表达明显增强,IL-1β水平显著升高,神经凋亡率及Bax蛋白表达升高,Bcl-2/Bax降低;与IS组比较,L-NA组脑缺血灶范围内TNF-α表达及IL-1β水平显著降低,神经凋亡率降低,Bcl-2蛋白表达及Bcl-2/Bax升高,Bax蛋白表达降低。结论:L-NA通过抑制TNF-α和IL-1β的升高,增加Bcl-2蛋白表达,降低Bax蛋白表达,调节Bcl-2/Bax平衡,对脑缺血大鼠脑神经元产生一定程度的保护作用。
To evaluate the effect of N^G-nitro-L-arginine（L-NA） on inflammatory factor and neuronal apoptosis after focal cerebral ischemic injury in rats and the possible mechanism of protective effect of L-NA against cerebral ischemic injury. Methods： Thirty male SD rats weighing 250-280 g were randomly divided into three groups（n = 10） ： （1）Sham operated group（SH）, （2）Isehemic group（IS）, （3）L-NA group. In L-NA group L-NA 20 mg/kg was given intraperitoneally twice a day for 3 consecutive days. In IS group normal saline was given instead of L-NA. Focal cerebral isehemia was produced by middle cerebral artery occlusion（MCAO） for 12 h. A nylon thread with rounded tip which was inserted into left internal carotid artery cranially until resistance was felt. The distance from bifurcation of common carotid artery to the tip of the thread was about 18 - 19 mm. Focal cerebral isehemia was confirmed by left Homer＇ s syndrome and right side hemiplegia. In SH group the carotid artery was exposed but no thread was inserted. The expression of TNF-α was determined by immunochemistry and the content of IL-1β was measured by radioimmunity. The Bcl-2 and Bax protein expression were detected by flow cytometry. Results： The expression of TNF-α and the content of IL-1 β were markedly increased after MCAO. Significantly increased DNA fragmentation indication of apoptosis was detected after MCAO. The expression of TNF-α and the content of IL-1 β was significantly lower in L-NA group than in IS group. The percentage of apoptosis cells and expression of Bax protein were markedly lower in L-NA group than in IS group but still significantly higher than in SH group. The expression of Bcl-2 protein was markedly higher in L-NA group than in IS group. There was no significant difference in the expression of Bcl-2 protein between IS and SH group. Conclusion： L-NA could inhibit the increase in the expression of TNF-α and the content of IL-1β, and protect neurons from apoptosis induced by focal cerebral ischemia through increasing the Bcl-2 protein expression and inhibiting the Bax protein expression.
出处
《中国应用生理学杂志》
CAS
CSCD
北大核心
2007年第4期446-449,共4页
Chinese Journal of Applied Physiology
基金
河北省自然科学基金资助项目(C2005000840)
关键词
L-硝基精氨酸
脑缺血
炎症因子
细胞凋亡
N^G-nitro-L-arginine
brain ischemia
inflammatory factor
apoptosis
