Protective mechanism of naoxinqing capsule in rat models of cerebral ischemia/reperfusion injury / 中国组织工程研究

ABSTRACT

BACKGROUND: Naoxinqing capsule has been used for treating cerebral ischemia/reperfusion injury for a long time. However, there are relatively few in-depth studies on its mechanism. OBJECTIVE: To investigate the therapeutic effect of Naoxinqing Capsule on gerbil model of cerebral ischemia/reperfusion injury by molecular biological means. METHODS: The study was approved by the Laboratory Animal Ethical Committee of Liaoning University of Chinese Medicine, approval No. 21000092017072. Eighty male Mongolian gerbils were randomly divided into sham, model, Naoxinqing and Naoluotong groups, and the latter three groups underwent bilateral common carotid artery clip for 5 minutes, to establish the model of cerebral ischemia/reperfusion injury. The sham group received no common carotid artery clip. Next day, the sham group fed normally, the model group was given normal saline, Naoxinqing group was given the 100 mg/(kg•d) Naoxinqing via gavage, and Naoluotong group given 100 mg/(kg•d) Naoluotong via gavage, respectively, for 21 consecutive days. The water maze test was conducted at 1 week before experiment ended. The brain tissue was removed after experiment. The learning and memory function, hippocampal neurons, cerebrovascular and corresponding molecular changes were detected. RESULTS AND CONCLUSION: (1) Compared with the sham group, the learning ability in the model group was decreased significantly. Naoxinqing and Naoluotong groups could effectively improve the learning ability after surgery. (2) Compared with the model group, the numbers of neurons in the Naoxinqing and Naoluotong groups were increased significantly, arranged regularly with clear contour and complete structure. (3) Compared with the model group, in the Naoxinqing and Naoluotong groups, the activities of superoxide dismutase and lactate dehydrogenase, and glutathione content were significantly increased, and the content of malonaldehyde was significantly decreased (P < 0.01). (4) The expression levels of ASC, NLRP3 and Caspase-1 in the hippocampus in the Naoxinqing and Naoluotong groups were significantly lower than those in the model group (P < 0.05). (5) The levels of interleukin-18 and interleukin-1β in the Naoxinqing and Naoluotong groups were significantly lower than those in the model group (P < 0.01). (6) Compared with the model group, the cells positive for platelet endothelial cell adhesion molecule-1 in the Naoxinqing and Naoluotong groups were significantly increased, the cells contacted closely each other. (7) Compared with the model group, in the Naoxinqing and Naoluotong groups, the expression levels of platelet endothelial cell adhesion molecule-1 and phosphorylated endothelial nitric oxide synthase were significantly up-regulated, and the content of nitric oxide was significantly increased (P < 0.01). (8) These results indicate that Naoxinqing and Naoluotong can effectively protect the morphology of hippocampal CA1 region in gerbils. Cerebral ischemia/reperfusion injury is accompanied by cerebral vascular dysfunction. Naoxinqing Capsule can protect cerebral vascular function and inhibit cerebral ischemia/reperfusion injury.