基于SIRT1/PGC-1α信号通路探讨同仁牛黄清心丸治疗后循环缺血性眩晕大鼠的作用机制
投稿时间:2024-04-30  修订日期:2024-05-27   点此下载全文
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作者中文名作者英文名单位中文名单位英文名E-Mail
陈霞 CHEN Xia 北京同仁堂股份有限公司科学研究所 Science Research Institute of Beijing Tong Ren Tang Limited by Share Ltd,Beijing jiumeionlyone@163.com 
刘丹 LIU Dan 北京同仁堂股份有限公司科学研究所 Science Research Institute of Beijing Tong Ren Tang Limited by Share Ltd,Beijing ld851031@sina.com 
张思玉 ZHANG Si-yu 北京同仁堂股份有限公司科学研究所 Science Research Institute of Beijing Tong Ren Tang Limited by Share Ltd,Beijing civic1124@qq.com 
朱晓光 ZHU Xiao-guang 北京同仁堂股份有限公司科学研究所 Science Research Institute of Beijing Tong Ren Tang Limited by Share Ltd,Beijing zxg85@sina.cn 
李晋生* LI Jin-sheng 北京同仁堂股份有限公司科学研究所 Science Research Institute of Beijing Tong Ren Tang Limited by Share Ltd,Beijing yarily@126.com 
基金项目:北京市中医药科技发展资金项目(BJZYYB-2023-51)
中文摘要:目的:探讨同仁牛黄清心丸对后循环缺血性眩晕大鼠脑损伤的保护作用机制。方法:采用手术结扎右侧颈总动脉和锁骨下动脉致大鼠右侧半脑不完全脑缺血建立后循环缺血性眩晕大鼠模型。分为假手术组,模型组,地芬尼多组,金纳多组,同仁牛黄清心丸高(2.4 g.kg-1)、中(1.2 g.kg-1)、低(0.6 g.kg-1)剂量组,观察同仁牛黄清心丸对旋转刺激后循环缺血性眩晕大鼠跳台潜伏期和前庭神经核血流量的影响,取大鼠右侧脑组织并测定脑组织中SOD、LDH活性和MDA、Lac含量,用Western blot法测定脑组织中SIRT1和PGC-1α蛋白表达水平。结果:同仁牛黄清心丸高、低剂量能明显缩短模型大鼠跳台逃避潜伏期,与模型组比较有显著性差异(均P<0.05);同仁牛黄清心丸高、中、低剂量能明显增加模型大鼠前庭神经核血流量(P<0.05);同仁牛黄清心丸高、中、低剂量能明显降低模型大鼠脑组织中LDH活性和Lac含量,与模型组比较有显著性差异(均P<0.01);同仁牛黄清心丸高、中、低剂量能明显降低模型大鼠脑组织中MDA含量和升高模型大鼠脑组织中SOD活力,与模型组比较有显著性差异(均P<0.01);同仁牛黄清心丸高、中剂量能明显升高模型大鼠脑组织SIRT1蛋白表达水平,与模型组比较有显著性差异(均P<0.05),同仁牛黄清心丸高、中、低剂量能明显升高模型大鼠脑组织PGC-1α蛋白表达水平,与模型组比较有显著性差异(均P<0.01)。结论:同仁牛黄清心丸能够增加脑缺血后前庭神经核血流量,减轻模型大鼠眩晕症状,通过调控SIRT1/PGC-1α信号通路,改善脑组织能量代谢,提高抗氧化能力,发挥神经保护作用。
中文关键词:同仁牛黄清心丸  后循环缺血性眩晕  SIRT1  PGC-1α
 
Discussion on the mechanism of Tongren Niuhuang Qingxin Pills in the treatment of posterior circulatin ischemic vertigo rats based on SIRT1/PGC-1α signaling pathway
Abstract:Objective: To explore the protective mechanism of Tongren Niuhuang Qingxin Pills against brain injury in posterior circulation ischemic vertigo rats. Methods: The rat model of posterior circulation ischemic vertigo was established by surgical ligation of the right common carotid artery and the subclavian artery. The rats were randomly divided into sham operation group, model group, Tongren Niuhuang Qingxin Pills 2.4、1.2、0.6 g.kg-1 groups. To observe the effect of Tongren Niuhuang Qingxin pills on the latency of platform jumping and vestibular nucleus blood flow in rats with circulatory ischemic dizziness after rotational stimulation, the activities of SOD and LDH and the contents of MDA and Lac in the right brain tissue of rats were determined. The expression levels of SIRT1 and PGC-1α in the brain tissue were determined by Western blot. Result: Tongren Niuhuang Qingxin pills at high and low doses could shorten the incubation period of model rats jumping to escape, and there were significant difference compared with model group (all P<0.05). Tongren Niuhuang Qingxin pills at high, medium and low doses could significantly increase the blood flow of vestibular nucleus in model rats, with significant differences compared with model group (P<0.05). Tongren Niuhuang Qingxin pills at high, medium and low doses could significantly reduce the activity of LDH and Lac content in brain tissue of model rats, with significant differences compared with model group (all P<0.01). Tongren Niuhuang Qingxin pills at high, medium and low doses could significantly reduce MDA content and increase SOD activity in brain tissue of model rats, with significant differences compared with model group (all P<0.01). Tongren Niuhuang Qingxin Pills at high and medium doses could significantly increase SIRT1 protein expression level in brain tissue of model rats, and there were significant differences compared with model group (all P<0.05). Tongren Niuhuang Qingxin Pills at high, medium and low doses could significantly increase PGC-1α protein expression level in brain tissue of model rats, and there were significant differences compared with model group (all P<0.01). Conclusions: Tongren Niuhuang Qingxin pills can increase the blood flow of the vestibular nucleus after cerebral ischemia and alleviate vertigo symptoms in model rats, improe brain energy metabolism and antioxidant capacity by regulating SIRT1/PGC-1α signaling pathway, and play a neuroprotective role.
keywords:Tongren Niuhuang Qingxin Pills  Posterior Circulation Ischemic Vertigo  SIRT1  PGC-1α
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