[艾灸对血管性痴呆大鼠海马CA1区肌醇需要酶1/X-box结合蛋白1通路的影响]

Fang Liu, Meng-Xing Li, Yu Wang, Wei Tang
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引用次数: 0

摘要

目的:观察艾灸督脉穴位对肌醇需要酶1(IRE1)的影响:观察艾灸督脉穴位对肌醇需要酶 1(IRE1)/X-盒结合蛋白 1(XBP1)的影响。/X-盒结合蛋白1(XBP1)通路,探讨其治疗血管性痴呆的机制:雄性SD大鼠随机分为正常组、假手术组、模型组、艾灸组和药物组(n=12)。n=12)。VD模型是通过永久结扎双侧颈总动脉建立的。艾灸组大鼠在 "百会穴"(GV20)、"大椎穴"(GV14)和 "风府穴"(GV15)处进行温和艾灸。和 "风府" (GV16)每点 20 分钟,每天一次,每周连续 6 天,共 4 周。药物组大鼠胃内灌注尼莫地平,每天3次,总剂量为2 mg-kg-1-d-1,共4周。采用莫里斯水迷宫试验检测建模前后和干预后大鼠的学习记忆能力。通过TUNEL染色检测海马CA1区神经细胞的凋亡率。大鼠海马CA1区IRE1、XBP1、B细胞淋巴瘤/白血病-2(Bcl-2)、Bcl-2相关X蛋白(Bax)的蛋白和mRNA表达水平,以及大鼠海马CA1区神经细胞凋亡率。结果表明:与假手术组相比,IRE1 XBP1、Belloma/ukemia-2(Bcl-2)、Bcl-2相关X蛋白(Bax)在海马CA1区的表达水平明显下降:结果:与假手术组相比,假手术组的平均逃逸潜伏期明显延长:艾灸督脉穴位可改善VD大鼠的认知功能,其机制可能与调节IRE1/XBP1通路,抑制促凋亡蛋白Bax的释放,增加抗凋亡蛋白Bcl-2的表达,从而抑制海马神经细胞的凋亡有关。
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[Effect of moxibustion on inositol requiring enzyme 1 / X-box binding protein 1 pathway in hippocampal CA1 region of rats with vascular dementia].

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

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