Lu Cui-Jie, Guo Yong-Zhen, Zhang Yang, Yang Lan, Chang Yue, Zhang Jing-Wen, Jing Li, Zhang Jian-Zhong
School of Basic Medical Science, Ningxia Key Laboratory of Cerebrocranial Diseases-Incubation Base of National Key Laboratory, Ningxia Medical University, Yinchuan 750004, China.
School of Basic Medical Science, Ningxia Key Laboratory of Cerebrocranial Diseases-Incubation Base of National Key Laboratory, Ningxia Medical University, Yinchuan 750004, China.
Pathol Res Pract. 2017 Sep;213(9):1191-1199. doi: 10.1016/j.prp.2017.06.005. Epub 2017 Jun 15.
The purpose of this study is to investigate the effect of coenzyme Q10 (CoQ10) on focal cerebral ischemia/reperfusion (I/R) injury in hyperglycemic rats and the possible involved mechanisms. In this study, we established the transient middle cerebral artery occlusion (MCAO) for 30min in the rats with diabetic hyperglycemia. The neurological deficit score, 2,3,5-triphenyltetrazolium chloride (TTC) staining and pathohistology are applied to detect the extent of the damage. The expression of Fis1, Mfn2 and Lc3 in the brain is investigated by immunohistochemical and Western blotting techniques. The results showed that the streptozotocin-induced diabetic hyperglycemia and MCAO-induced focal cerebral ischemia were successfully prepared in rats. In the hyperglycemic group, the neurological deficit scores, infarct volumes, and number of pyknotic cells were higher than that in the normalglycemic group at 24h and/or 72h reperfusion. Pretreated with CoQ10 (10mg/kg) for four weeks could significantly reduce the neurological scores, infarct volume, and pyknotic cells at 24h and/or 72h reperfusion of the hyperglycemic rats compared with non-CoQ10 pretreated hyperglycemic animals. Immunohistochemistry and Western blotting showed that pretreatment with CoQ10 or insulin could significantly reduce the expression of Fis1 protein in the brain at 24h and 72h reperfusion. Inversely, a significantly increased expression of Mfn2 was observed in the rats CoQ10 or insulin pretreated at 24h and/or 72h reperfusion when compared with matched hyperglycemic rats. These results demonstrated that hyperglycemia could aggravate ischemic brain injury. Pretreatment with CoQ10 might ameliorate the diabetic hyperglycemia aggravated I/R brain damage in the MCAO rats by maintain the balance between mitochondrial fission and fusion.
本研究旨在探讨辅酶Q10（CoQ10）对高血糖大鼠局灶性脑缺血/再灌注（I/R）损伤的影响及其可能的相关机制。在本研究中，我们在糖尿病高血糖大鼠中建立了短暂性大脑中动脉闭塞（MCAO）30分钟的模型。应用神经功能缺损评分、2,3,5-三苯基氯化四氮唑（TTC）染色和病理组织学来检测损伤程度。通过免疫组织化学和蛋白质印迹技术研究大脑中Fis1、Mfn2和Lc3的表达。结果表明，成功制备了链脲佐菌素诱导的糖尿病高血糖和MCAO诱导的局灶性脑缺血大鼠模型。在高血糖组中，再灌注24小时和/或72小时时，神经功能缺损评分、梗死体积和固缩细胞数量均高于正常血糖组。与未用CoQ10预处理的高血糖动物相比，用CoQ10（10mg/kg）预处理四周可显著降低高血糖大鼠再灌注24小时和/或72小时时的神经功能评分、梗死体积和固缩细胞数量。免疫组织化学和蛋白质印迹显示，CoQ10或胰岛素预处理可在再灌注24小时和72小时时显著降低大脑中Fis1蛋白的表达。相反，与匹配的高血糖大鼠相比，在再灌注24小时和/或72小时时用CoQ10或胰岛素预处理的大鼠中观察到Mfn2表达显著增加。这些结果表明，高血糖可加重缺血性脑损伤。CoQ10预处理可能通过维持线粒体分裂与融合之间的平衡来改善糖尿病高血糖加重的MCAO大鼠I/R脑损伤。
