甘草酸二铵对大鼠脑缺血-再灌注损伤的保护作用

Diammonium glycyrrhizinate attenuates cerebral ischemia-reperfusion injury by Akt/caspase-3 pathway in rats

目的探讨甘草酸二铵对大鼠脑缺血一再灌注损伤的作用。方法将30只雄性sD大鼠（体重为250～300g）随机分为假手术组、甘草酸二铵组、模型组，每组10只。采用可逆性大脑中动脉线栓法制作大鼠局灶性脑缺血-再灌注损伤模型。采用Zea—Longa评分评估大鼠神经功能。运用尼氏体染色检测大鼠海马组织尼氏小体数量，免疫组化法检测大鼠海马组织Akt、caspase-3阳性细胞数量。结果术后24h甘草酸二铵组和模型组大鼠Zea—Longa评分明显高于假手术组（P〈0．05）；造模后3d，甘草酸二铵组神经功能较模型组明显改善（P〈0．05）。甘草酸二铵组海马组织尼氏小体数量和Akt阳性细胞数量较模型组明显增加，而caspase-3阳性细胞数量较模型组明显减少（P〈0．05）。结论甘草酸二铵可通过Akt／caspase-3途径减轻脑缺血一再灌注损伤大鼠细胞凋亡，发挥对大鼠缺血一再灌注损伤的保护作用。

Objective To study the effect of diammonium glycyrrhizinate （DG） on cerebral ischemia-reperfusion injury in rats. Methods Thirty SD rats were randomly divided into 3 groups, i.e. sham operation group （n=10）, model group （n=10） and DG treatment group （n=10）. The rat model of focal cerebral ischemia-reperfusion injury was made by reversible middle cerebral artery occlusion in rats. The rats in DG traetment group received intraperitoneal injection of DG [20 mg/（kg.d）, qd] for 3 days, and the rats in sham operation and model groups received intraperitoneal injection of indentical volume of physiological saline. Zea-longa score was used to assess the neurological function 2 hours and 3 days after the injury. The number of Nissl bodies of neurons was assess by Nissl＇s staining and the numbers of caspase-3 positive cells and Akt positive cells were detected by immunohistochemistry staining in the hippocampus tissues 3 days after the injury. Results Two hours after injury, the Zea-longa scores in DG treatment group [（2.60±0.51） points] and model group [（2.59 ± 0.54） points] were significantly higher than that （zero point） in sham operation group （P〈0.05）, and there was no significant difference between DG treatment and model groups （P〉0.05）. Three clays after injury, the Zea-longa score in DG treatment group [（1.90± 0.74） points] was still significantly higher than that （zero point） in sham operation group （P〈O.05）, and significantly lower than that [（2.50±0.48） points] in model group （P〈0.05）. The numbers of Nissl bodies of neurons and Akt positive cells in DG treatment group were significantly more than that in model group （P〈0.05）, and the number of caspase-3 positive cells in DG treatment group was significantly fewer than that in model group （P〈0.05）. Conclusion It is suggested that DG can reduce the level of neuron apoptosis by Akt/easpase-3 pathway, thus protect the cerebral tissues after the cerebral ischemia-reperfusion injury in the rats.