Single versus multiple administrations of metformin in treatment of rats with ventilator-induced brain injury
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摘要: 目的 探讨二甲双胍单次和多次给药对大鼠机械通气性脑损伤的影响。 方法 将健康成年雄性Wistar大鼠24只采用随机数字表法分为对照组(C组)、机械通气组(MV组)、机械通气+单次二甲双胍组(MET组)、机械通气+多次二甲双胍组(M-MET组)。C组气管插管后保留自主呼吸,不行机械通气; MV组、MET组和M-MET组均行机械通气。MET组实验前喂食二甲双胍500 mg/kg, M-MET组实验前连续4周喂食二甲双胍500 mg/(kg·d)。机械通气后处死大鼠取脑组织,光镜下观察病理学结果,用酶联免疫吸附测定(ELISA)法测定脑组织匀浆上清液的白介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)水平,用试剂盒测定超氧化物歧化酶(SOD)和丙二醛(MDA)水平。 结果 C组海马组织未见明显病理学改变,另3组病理学损伤严重, MET组损伤较MV组明显减轻, M-MET组病理学改变介于MET组与MV组之间。与C组相比, MV组、MET组、M-MET组的IL-6、TNF-α、MDA水平升高, SOD水平降低,差异有统计学意义(P < 0.05); 与MV组相比,MET和M-MET组IL-6、TNF-α、MDA水平降低, SOD水平升高,差异有统计学意义(P < 0.05); 与MET组相比, M-MET组IL-6、TNF-α和MDA水平升高, SOD水平降低,差异有统计学意义(P < 0.05)。 结论 二甲双胍可减轻机械通气诱发的大鼠脑损伤,其机制可能与抑制炎性通路和氧化应激有关,且单次给药的效果优于多次给药。Abstract: Objective To investigate effect of single and multiple administrations of metformin on treatment of rats with ventilator-induced brain injury. Methods A total of 24 healthy adult male Wistar rats were randomly divided into 4 groups, including control group(group C, n=6), mechanical ventilation group(MV group, n=6), mechanical ventilation combined with single-does metformin group(MET group, n=6), and mechanical ventilation with multiple-does metformin group(M-MET group, n=6). Group C retained spontaneous breathing after endotracheal intubation without mechanical ventilation. MV group, MET group and M-MET group were performed mechanical ventilation. Metformin was fed 500 mg/kg in the MET group before the experiment and 500 mg/(kg·d)in the M-MET group for 4 weeks. At the end of mechanical ventilation, all rats were sacrificed for brain tissue to observe pathological changes under light microscope. Interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)of brain tissue homogenate were measured by Enzyme linked immunosorbent assay(ELISA)kits, superoxide dismutase(SOD)and malondialdehyde(MDA)were measured with kits. Results Compared with group C, MV group, MET group and M-MET group had severe pathological damage, the contents of IL-6, TNF-α and MDA significantly increased, while the level of SOD decreased significantly(P < 0.05). Compared with MV group, pathological damage of the MET and - M-MET groups were alleviated, the levels of IL-6, TNF-α and MDA significantly decreased, and the level of SOD significantly increased(P < 0.05). Compared with MET group, the levels of IL-6, TNF-α, MDA and SOD in M-MET group were significantly higher(P < 0.05). Conclusion Metformin can reduce the brain injury induced by mechanical ventilation in rats. The mechanism may be related to the inhibition of inflammatory pathway and oxidative stress, and the effect of single administration is better than that of multiple administration.
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Keywords:
- metformin /
- mechanical ventilation /
- brain injury /
- inflammation /
- rats
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