Effect of moxibustion on inositol requiring enzyme 1 / X-box binding protein 1 pathway in hippocampal CA1 region of rats with vascular dementia

Abstract

To observe the effect of moxibustion at Governor Vessel acupoints on inositol requiring enzyme 1 （IRE1） / X-box binding protein 1 （XBP1） pathway in hippocampal CA1 region of rats with vascular dementia （VD）, so as to explore its mechanisms in the treatment of VD. Male SD rats were randomly divided into normal, sham operation, model, moxibustion （Moxi） and medication groups （n=12）. The VD model was established by permanent ligation of bilateral common carotid arteries. For rats of the Moxi group, mild moxibustion was given to "Baihui" （GV20）, "Dazhui" （GV14） and "Fengfu" （GV16） for 20 min each point, once a day for consecutive 6 days per week, for a total of 4 weeks. For rats of the medication group, intragastric perfusion of nimodipine was given 3 times each day with total dose of 2 mg•kg-1•d-1 for 4 weeks. Morris water maze test was used to detect the learning and memory ability of rats before and after modeling as well as after intervention. The apoptosis rate of nerve cells in hippocampal CA1 region was detected by TUNEL staining. The proteins and mRNA expression levels of IRE1, XBP1, B-cell lymphoma/leukemia-2 （Bcl-2）, Bcl-2 associated X protein （Bax） in hippocampal CA1 region were detected by Western blot and real-time quantitative PCR, respectively. Compared with the sham operation group, the average escape latency was significantly prolonged （P<0.01）, the number of times crossing the original platform was significantly reduced （P<0.01）, the apoptosis rate of nerve cells in hippocampal CA1 region was significantly increased （P<0.01）, the proteins and mRNA expression levels of IRE1, XBP1 and Bax were significantly increased （P<0.01）, and the expression levels of Bcl-2 protein and mRNA were significantly decreased （P<0.01） in rats of the model group. After treatment, compared with the model group, the average escape latency was significantly shortened （P<0.01）, the number of times crossing the original platform was increased （P<0.05）, the apoptosis rate of nerve cells in hippocampal CA1 region was significantly decreased （P<0.01）, the protein and mRNA expression levels of IRE1, XBP1 and Bax were decreased （P<0.05, P<0.01）, and the expression levels of Bcl-2 protein and mRNA were increased （P<0.05, P<0.01） in rats of the Moxi group and medication group. There was no significant difference in the above indexes between the Moxi group and the medication group. Moxibustion at the acupoints of Governor Vessel can improve the cognitive function of VD rats, and its mechanism may be related to regulating IRE1/XBP1 pathway, inhibiting the release of pro-apoptotic protein Bax, increasing the expression of anti-apoptotic protein Bcl-2, and thus inhibiting the apoptosis of hippocampal nerve cells.