硫化氢对大鼠局灶性脑缺血再灌注损伤的保护效果研究

Experimental study on protective effect of H2S on focal cerebral ischemia-reperfusion injury in rats

摘要:

目的 探讨硫化氢（H2S）干预处理对大脑中动脉栓塞局灶性脑缺血性再灌注损伤（CIRI）模型大鼠脑及神经功能的保护作用及其机制。方法 选取48 只成年雄性SD 大鼠，采用随机数字表法分为假手术组、模型组和实验组，每组16 只（复制模型过程中如死亡则补足），假手术组和实验组采用线栓法结扎大鼠左侧大脑中动脉复制模型，实验组于栓线后10 min 腹腔注射25μmol/kg 硫氢化钠NaHS 生理盐水，假手术组和模型组仅给予等体积生理盐水。结果 实验组大鼠的死亡率为23.81%，低于模型组的44.83%，两组比较，差异有统计学意义（P <0.05）；3 组大鼠的脑梗死体积百分比比较，差异有统计学意义（P <0.05）。模型组和实验组大鼠的脑梗死体积百分比高于假手术组；实验组的脑梗死体积百分比低于模型组；3 组大鼠的海马CA1 区的PI3K、p-Akt、Caspase 蛋白水平比较，差异有统计学意义（P <0.05），模型组大鼠海马CA1 区的p-Akt、Caspase 蛋白高于假手术组，实验组大鼠海马CA1 区的Caspase 蛋白低于于模型组，实验组大鼠海马CA1 区的PI3K、p-Akt 蛋白高于假手术组和模型组。结论 H2S 干预处理对大脑中动脉栓塞局灶性脑缺血再灌注损伤模型大鼠有脑脊神经缺损功能保护作用，其作用机制可能与激活PI3K、p-Akt 通路，抑制凋亡相关蛋白Caspase 有关。

Abstract:

Objective To investigate the protective effect of hydrogen sulfide (H2S) on the brain and nerve function in rats after focal cerebral ischemia-reperfusion injury and its mechanism. Methods Forty-eight adult male SD rats were randomly divided into sham group, model group and experimental group with 16 in each group (the number was complemented in case of death during modeling process). In the model group and the experimental group, suture method was used to ligate the left middle cerebral artery of the rats for modeling; 10 min after suture,the experimental group had intraperitoneal injection of 25 μmol/kg NaHS saline solution, but the sham group and the model group only received equal volume of saline. Results The mortality rate of 23.81% in the experimental group was significantly lower than 44.83% in model group (P < 0.05). The percentage of cerebral infarct volume in the model group and the experimental group was significantly higher than that in the sham group (P < 0.05); the infarct volume percentage of the experimental group was significantly lower than that of the model group (P < 0.05).p-Akt and caspase in the hippocampal CA1 region of the model group were significantly higher than those of the sham group (P < 0.05) . Caspase protein in the hippocampal CA1 region of the rats in the experimental group was significantly lower than that in the model group (P < 0.05). PI3K and p-Akt in the hippocampal CA1 region of the rats in the experimental group were significantly higher than those in the sham group and the model group(P < 0.05). Conclusions H2S intervention has protective effect on brain spinal nerve function in the treatment of focal cerebral ischemia-reperfusion injury rat model due to cerebral artery occlusion, its mechanism may be related to the activation of PI3K/p-Akt pathway and inhibition of apoptosis-related protein caspase.