复方脑肽节苷脂注射液激活线粒体自噬改善脑缺血再灌注损伤

Effect of Compound Porcine Cerebroside and Ganglioside Injection on Cerebral Ischemia-reperfusion Injury in Rats

目的观察复方脑肽节苷脂注射液(CPCGI)对大鼠脑缺血再灌注损伤的保护作用并探讨其机制。方法 Sprague-Dawley大鼠随机分成假手术组、模型组、CPCGI低剂量治疗组、CPCGI高剂量治疗组、阳性药金纳多组,每组10只。线栓法制备大鼠大脑中动脉梗阻2 h后复灌模型,即刻给药,连续14 d。术后1 d、3 d、7 d和14 d行神经功能症状缺损评分,术后14 d行贴纸去除及平衡木行走实验,Western blotting检测损伤周围脑组织Beclin1、PINK1及Parkin的表达。结果术后14 d,与模型组相比,各给药组大鼠神经功能缺损评分降低(P<0.05),大鼠过杆时间明显缩短(P<0.01),CPCGI给药组去除两侧前肢贴纸的时间缩短(P<0.05)。模型组皮层组织中Beclin1及Parkin蛋白表达明显下降(P<0.01),PINK1蛋白表达明显上升(P<0.01),CPCGI各组均能逆转该作用(P<0.05)。结论 CPCGI的神经保护作用机制之一可能与激活线粒体自噬,改善线粒体功能有关。

Objective To investigate the neuroprotective effect and possible mechanism of Compound Porcine Cerebroside and Ganglioside Injection（CPCGI） on cerebral ischemia-reperfusion injury in rats. Methods Healthy adult male Sprague-Dawley rats were divided into sham group（n=10）, model group（n=10）, CPCGI low dosage group（n=10） and high dosage group（n=10）, and control group（Ginkgo biloba extract, n=10）. All the rats was subjected to middle cerebral artery occlusion（MCAO） for two hours and reperfusion except sham group, and received treatment for fourteen days once reperfusion started. They were tested with modified Neurological Severity Score one, three, seven and fourteen days after MCAO, and adhesive- removal test and beam- walking test fourteen days after MCAO. The expression of Beclin1,PINK1 and Parkin were detected with Western blotting. Results Compared with the model group, the Neurological Severity Score reduced（P〈0.05） and the time crossing the beam reduced（P〈0.01） in all the medical groups fourteen days after MCAO, and the time removing the adhesive paper reduced in the CPCGI groups（P〈0.01）. The expression of Beclin1 and Parkin decreased and the PINK1 level increased in the model group（P〈0.01）, and it was reversed in all the CPCGI groups（P〈0.05）. Conclusion CPCGI could relieve the cerebral ischemia-reperfusion injury in rats through the regulation in mitophagy.