Wang Tingting, Zhao Li, Guo Yunliang, Zhang Meizeng, Pei Haitao
Institute of Cerebrovascular Diseases, Affiliated Hospital of Qingdao University, Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders; Taishan Scholars Construction Project Excellent Innovative Team of Shandong Province, Qingdao, 266003, P. R. China.
PLoS One. 2015 Apr 30;10(4):e0124099. doi: 10.1371/journal.pone.0124099. eCollection 2015.
This paper aimed to explore the protective effects of picroside II against the neuronal apoptosis and changes in morphology and structure that follow cerebral ischemic injury in rats. A focal cerebral ischemic model was established by inserting a monofilament thread to achieve middle cerebral artery occlusion (MCAO) in 60 Wistar rats, and intraperitoneal injections of picroside II (20 mg/kg) were administered. The neurobehavioral functions were evaluated with the modified neurological severity score (mNSS) test. The cerebral infarct volumes were measured with tetrazolium chloride (TTC) staining. The morphology and ultrastructure of the cortical brain tissues were observed with hematoxylin-eosin staining and transmission electron microscopy, respectively. The apoptotic cells were counted with terminal deoxynucleotidyl transferase dUTP nick-end labeling and flow cytometry, and pERK1/2 expression was determined by immunohistochemical assay and Western blot. The results indicated that neurological behavioral malfunctions and cerebral infarcts were present in the MCAO rats. In the model group, the damage to the structures of the neurons and the blood brain barrier (BBB) in the cortex was more severe, and the numbers of apoptotic cells, the early apoptotic ratio (EAR) and pERK1/2 expression were significantly increased in this group compared to the control group (P<0.05). In the treatment group, the neurological behavioral function and the morphology and ultrastructure of the neurons and the BBB were improved including the number of Mi increased and relative area of condensed chromosome and basement (BM) thickness descreased, and the cerebral infarct volume, the number of apoptotic cells, the EAR and pERK1/2 expression were significantly decreased compared to the model group (P<0.05). These results suggest that picroside II reduced apoptosis and improved the morphology and ultrastructure of the neurons and the BBB and that these effects resulted in the recovery of the neurobehavioral function of rats with cerebral ischemia.
本文旨在探讨胡黄连苷II对大鼠脑缺血损伤后神经元凋亡以及形态和结构变化的保护作用。通过插入单丝尼龙线建立局灶性脑缺血模型，使60只Wistar大鼠大脑中动脉闭塞（MCAO），并腹腔注射胡黄连苷II（20 mg/kg）。采用改良神经功能缺损评分（mNSS）测试评估神经行为功能。用氯化三苯基四氮唑（TTC）染色测量脑梗死体积。分别用苏木精-伊红染色和透射电子显微镜观察大脑皮质组织的形态和超微结构。用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法和流式细胞术计数凋亡细胞，并用免疫组织化学测定法和蛋白质免疫印迹法测定pERK1/2表达。结果表明，MCAO大鼠存在神经行为功能障碍和脑梗死。在模型组中，皮质神经元和血脑屏障（BBB）结构的损伤更严重，与对照组相比，该组凋亡细胞数量、早期凋亡率（EAR）和pERK1/2表达显著增加（P<0.05）。在治疗组中，神经行为功能以及神经元和BBB的形态和超微结构得到改善，包括线粒体数量增加、染色体凝聚相对面积和基底膜（BM）厚度减小，与模型组相比，脑梗死体积、凋亡细胞数量、EAR和pERK1/2表达显著降低（P<0.05）。这些结果表明，胡黄连苷II减少了细胞凋亡，改善了神经元和BBB的形态和超微结构，这些作用导致脑缺血大鼠神经行为功能的恢复。
