关键词: 脑卒中, 吞咽障碍, 短暂性大脑中动脉栓塞, 孤束核, 5-羟色胺, BAX, BCL-2

Abstract: BACKGROUND: The treatment of post-stroke dysphagia with Lipopharyngeal Qibi Formula has achieved good efficacy, and 5-hydroxytryptamine in peripheral serum and neurotransmitters in the nucleus tractus solitarius are closely related to swallowing. Therefore, this study was conducted to explore the modulatory effects of peripheral serum and nucleus tractus solitarius neurotransmitters in swallowing by using modern medical experimental methods such as molecular biology, thereby developing new ideas for the exploration of their mechanisms. 
OBJECTIVE: To verify the therapeutic effect of Lipopharyngeal Qibi Formula on post-stroke dysphagia and to investigate its mechanism of action.  
METHODS: Thirty-eight Sprague-Dawley rats were randomly divided into model group (n=14), treatment group (n=14) and sham-operated group (n=10). Animals in the model and treatment groups were modeled by reperfusion after 90 minutes of transient cerebral ischemia by wire bolus method. At 6 hours after modeling, neurological function was scored, and rats with a score of 2 were selected for subsequent experiments. The treatment group was given compound Lipopharyngeal Qibi Formula by gavage starting from the 2nd day after modeling and the remaining two groups were given normal saline by gavage. Changes in body mass, 24-hour food and water intake were recorded on days 2, 7, 14 and 30. The swallowing initiation response time and the number of swallows were detected using a biosignal collector and a tonic transducer on days 14 and 30. After the swallowing test, the ischemic area of the brain in each group was measured by TTC staining. The expression of 5-hydroxytryptamine in the nucleus tractus solitarius of the medulla oblongata was measured by immunohistochemistry. The mRNA and protein expression levels of BCL-2 and BAX in the insula, premotor cortex, cingulate cortex and thalamus of rats in each group were measured by RT-PCR and Western blot, respectively.
RESULTS AND CONCLUSION: Compared with the sham-operated group, the body mass, 24-hour food intake and water intake were reduced, the swallow initiation response time was prolonged, and the number of swallows was reduced in the treatment and model groups at day 14 of gavage (P < 0.05). Compared with the model group, the body mass, 24-hour food intake and water intake of rats were increased in the treatment group at day 30 of gavage (P < 0.05), but were still lower than those in the sham-operated group. Compared with the model group, the swallow initiation reaction time was shortened and the number of swallows increased in the treatment group, but the number of swallows was still significantly lower than that in the sham-operated group (P < 0.05). Cerebral ischemia area was reduced in the treatment group compared with the model group, and the number of 5-hydroxytryptamine-positive cells in the nucleus tractus solitarius of the medulla oblongata was increased in the treatment group compared with the model group, but it was still significantly lower than that in the sham-operated group (P < 0.05). Compared with the model group, the expression of BCL-2 mRNA and protein in the insula, cingulate cortex and thalamus of rats in the treatment group were significantly increased, the expression of BAX mRNA and protein were significantly decreased, and the BCL-2/BAX ratio was significantly increased (P < 0.05). To conclude, the Chinese herbal compound Lipopharyngeal Qibi Formula could improve the number of swallows and swallowing initiation response time, as well as 24-hour food intake, body mass and other swallowing-related indexes in rats with post-stroke dysphagia. The mechanism of action may be achieved by improving the area of cerebral ischemia, inhibiting the apoptosis of neuronal cells in the insula, cingulate cortex and thalamus of rats, thus improving the regulation of the higher centers on the medulla oblongata swallowing center, and regulating the level of 5-hydroxytryptamine in the nucleus tractus solitarius.

Key words: stroke, dysphagia, transient middle cerebral artery occlusion, nucleus tractus solitarius, 5-hydroxytryptamine, BAX, BCL-2