Journal of Shanghai Jiao Tong University (Science) ›› 2019, Vol. 24 ›› Issue (6): 723-731.doi: 10.1007/s12204-019-2127-x

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Reduction of Brain Injury After Stroke in Hyperglycemic Rats via Fasudil Pretreatment

LIU Jianyu (刘健宇), MU Zhihao (木志浩), WANG Liping (王丽萍), WEN Ruoxue (闻若雪), WANG Yongting (王永亭), YANG Guoyuan (杨国源), ZHANG Zhijun (张志君)   

  1. (1. Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China; 2. Department of Pathology and Pathophysiology, Faculty of Basic Medical Sciences, Kunming Medical University, Kunming 650500, China; 3. Department of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China)
  • 出版日期:2019-12-15 发布日期:2019-12-07
  • 通讯作者: ZHANG Zhijun (张志君) E-mail:zhangzj@sjtu.edu.cn

Reduction of Brain Injury After Stroke in Hyperglycemic Rats via Fasudil Pretreatment

LIU Jianyu (刘健宇), MU Zhihao (木志浩), WANG Liping (王丽萍), WEN Ruoxue (闻若雪), WANG Yongting (王永亭), YANG Guoyuan (杨国源), ZHANG Zhijun (张志君)   

  1. (1. Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China; 2. Department of Pathology and Pathophysiology, Faculty of Basic Medical Sciences, Kunming Medical University, Kunming 650500, China; 3. Department of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China)
  • Online:2019-12-15 Published:2019-12-07
  • Contact: ZHANG Zhijun (张志君) E-mail:zhangzj@sjtu.edu.cn

摘要: Diabetes is usually associated with cerebrovascular disease, especially stroke. In practice, fasudil is widely accepted to be applied for the treatment of vascular disease. This article demonstrates the study concentrating on the effects of fasudil pretreatment on the prognosis of diabetic stroke. 250—300 g Sprague- Dawley rats were randomly divided into three groups, non-diabetic stroke group, diabetic stroke group, and fasudil pretreatment group. The rats of diabetes group were treated with intraperitoneal injection of streptozotocin (60 mg/kg), in the meantime the same dose of citrate buffer was injected into those of the control group. The rats of the fasudil group received daily fasudil intraperitoneal injection at 10 mg/kg for three consecutive weeks. After four weeks, all the rats of the experimental group were treated with middle cerebral artery occlusion for 90 min. After sacrifice, the fresh brain samples were collected for following experiments, including infarct volume, edema volume, blood-brain barrier (BBB), which were detected by immunohistochemistry. Inflammatory factors were examined by real-time polymerase chain reaction (RT-PCR) using tissue Ribonucleic Acid (RNA). The concentration of blood glucose is 15 mmol/L or more, which proved that the diabetes model was a success. Fasudil pretreatment decreases the percentage of stroke mortality of diabetes from 43.75% to 31.25%, while the infarction volume decreases from 52.95% ± 12.7% to 45.97% ± 6.7%. Gap formation of tight junction and Immunoglobulin G (IgG) leakage were reduced (P < 0.05), and the expression of inflammatory factors decreases (P < 0.05) in fasudil pretreatment after diabetic stroke. Diabetes aggravates the mortality of cerebral ischemic rats. Prolonged fasudil pretreatment can reduce mortality of diabetic stroke, decrease cerebral infarction volume and undermine inflammatory factors expression, and protect the BBB.

关键词: diabetes, stroke, fasudil pretreatment, blood-brain barrier (BBB)

Abstract: Diabetes is usually associated with cerebrovascular disease, especially stroke. In practice, fasudil is widely accepted to be applied for the treatment of vascular disease. This article demonstrates the study concentrating on the effects of fasudil pretreatment on the prognosis of diabetic stroke. 250—300 g Sprague- Dawley rats were randomly divided into three groups, non-diabetic stroke group, diabetic stroke group, and fasudil pretreatment group. The rats of diabetes group were treated with intraperitoneal injection of streptozotocin (60 mg/kg), in the meantime the same dose of citrate buffer was injected into those of the control group. The rats of the fasudil group received daily fasudil intraperitoneal injection at 10 mg/kg for three consecutive weeks. After four weeks, all the rats of the experimental group were treated with middle cerebral artery occlusion for 90 min. After sacrifice, the fresh brain samples were collected for following experiments, including infarct volume, edema volume, blood-brain barrier (BBB), which were detected by immunohistochemistry. Inflammatory factors were examined by real-time polymerase chain reaction (RT-PCR) using tissue Ribonucleic Acid (RNA). The concentration of blood glucose is 15 mmol/L or more, which proved that the diabetes model was a success. Fasudil pretreatment decreases the percentage of stroke mortality of diabetes from 43.75% to 31.25%, while the infarction volume decreases from 52.95% ± 12.7% to 45.97% ± 6.7%. Gap formation of tight junction and Immunoglobulin G (IgG) leakage were reduced (P < 0.05), and the expression of inflammatory factors decreases (P < 0.05) in fasudil pretreatment after diabetic stroke. Diabetes aggravates the mortality of cerebral ischemic rats. Prolonged fasudil pretreatment can reduce mortality of diabetic stroke, decrease cerebral infarction volume and undermine inflammatory factors expression, and protect the BBB.

Key words: diabetes, stroke, fasudil pretreatment, blood-brain barrier (BBB)

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