| Objective:Cognitive dysfunction has a greater impact on the social life of patients in many clinical symptoms of depressive episodes.The main area of the brain that controls cognitive function is the prefrontal lobe.Improving cognitive function is of great significance for depressive episodes and treatment.To this end,we used a chronic unpredictable stress stimulus combined with orphans to establish a model of depression in rats,and observed the prefrontal cortical region of rats with depressive episodes by behavioral,pathological changes and expression of mitochondrial apoptosis-related proteins.Yuan changed the situation,and studied the role and therapeutic mechanism of traditional Chinese medicine Keyu Shushen Granules and western medicine fluoxetine in the prefrontal cortex of rats with depressive episodes.Thereby exploring new ways to treat depressive episodes.Methods:A model of depression was established by chronic unpredictable stress stimulation combined with orphanage.The experimental animals were randomly divided into 6 groups(n=15):blank group,model group,low-dose Chinese medicine group,middle-medication medium-dose group,high-dose Chinese medicine group,western medicine fluoxetine group.Behavioral changes in depressed rats were measured by Open-field experiment,Morris water maze test and sugar water consumption test.The changes and pathological changes of prefrontal neurons in depressed rats were observed by HE staining.Westem blot and RT-PCR were used to analyze the expression of mitochondrial apoptosis pathway-related proteins AIF,Cyt-c and Apaf-1 and the corresponding gene expression differences.The expression of apoptosis-related proteins in the prefrontal mitochondria of each group of depressed rats was observed by immunohistochemistry.Data were analyzed using SPSS 20.0 and the results were expressed as mean ± standard deviation('x ± s).All experimental data were analyzed by homogeneity of variance,and one-way analysis of variance and t test were used.All statistical tests were performed by two-sided test.P<0.05 indicated that the difference of the tested indicators was statistically significantResults:Animal models were established after 2 weeks of application of unpredictable stress stimuli and orphans.The behavior of the animals showed significant depression-like behavior.Compared with the blank group,the scores of Open-field experiments in the other groups were significantly lower than those in the blank group(p<0.05).The latency of the low-position navigation test in the other groups of Morris water maze test was significantly higher than that in the blank group(p<0.05).At the same time,the percentage of sugar water consumption in the other groups also decreased significantly.lt indicated that the rat model of depression was established successfully,and the depressed rats in each group showed obvious depressive symptoms such as apathy,low excitability and cognitive impairment.After administration,the scores of Open-field test in the low,medium and high dose groups of Chinese medicine and western medicine group were significantly higher than those in the model group(p<0.05),and the latency of Morris water maze test was significantly lower than that in the model group(p<0.05).The percentage of sugar water consumption in each group administered at the same time was also higher than that in the model group.Western blot analysis showed that the expression of AIF,Cyt-c and Apaf-1 protein was significantly lower than that of the model(p<0.05).There was no significant difference between the western medicine group and the model group(p>0.05)..The results of RT-PCR showed that the mRNA content of Apaf-1 and Cyt-c protein in the drug-administered group was higher than that in the blank group.Compared with the model group,the expression of Cyt-c in the drug-administered group was not significantly different,and the expression of Apaf-1 was significantly different.The results of immunohistochemistry showed that compared with the blank group,the apoptosis of the prefrontal cells in the model group and each administration group was aggravated,the cells were arranged loosely,and the cell morphology changed greatly.The cell morphology and apoptosis of each drug-administered group were smaller than those of the model group,and the expression of AIF and Cyt-c protein was less than that of the model group.Conclusion:The expression of mitochondrial apoptosis pathway-related proteins AIF,Cyt-c and Apaf-1 is increased in the prefrontal cortex of depressive rats,indicating that the degree of apoptosis in the prefrontal cortex is increased in rats with depressive episodes.Granules can ameliorate the prefrontal lobe apoptosis in depressed rats by attenuating the mitochondrial apoptotic pathway while reducing the clinical manifestations of depressive episodes. |
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