| 引用本文: | 杨蕙,韩远山,柳卓,孟盼,杜青,赵洪庆,龙红萍,王宇红.左归降糖解郁方对糖尿病并发抑郁症大鼠下丘脑信号通路的影响[J].中国现代应用药学,2019,36(11):1333-1337. |
| YANG Hui,HAN Yuanshan,LIU Zhuo,MENG Pan,DU Qing,ZHAO Hongqing,LONG Hongping,WANG Yuhong.Effect of Zuogui Jiangtang Jieyu Formulation on Signaling Pathway in Hypothalamus of Diabetic Rats with Depression[J].Chin J Mod Appl Pharm(中国现代应用药学),2019,36(11):1333-1337. |
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| 左归降糖解郁方对糖尿病并发抑郁症大鼠下丘脑信号通路的影响 |
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杨蕙1, 韩远山1, 柳卓2, 孟盼2, 杜青3, 赵洪庆2, 龙红萍1, 王宇红2,4
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1.湖南中医药大学第一附属医院, 长沙 410007;2.湖南中医药大学湖南省中药粉体与创新药物省部共建国家重点实验室培育基地, 长沙 410208;3.湖南省中医药研究院, 长沙 410006;4.湖南中医药大学中医学国内一流建设学科, 长沙 410208
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| 摘要: |
| 目的 研究左归降糖解郁方对糖尿病并发抑郁症大鼠下丘脑sigma-1受体/蛋白激酶C（sigma-1 receptor/protein kinase C，sigma-1R/PKC）信号通路的影响。方法 建立糖尿病并发抑郁症的动物模型，并随机分为4组：模型组、阳性药组、左归降糖解郁方高剂量组（20.53 g·kg-1）、左归降糖解郁方低剂量组（10.26 g·kg-1），另设健康SD大鼠为正常组。灌胃给药28 d后，各组大鼠尾静脉取血检测血糖含量，开野试验检测大鼠的自主活动能力，HE染色检测大鼠下丘脑的病理损伤情况，ELISA法检测大鼠下丘脑匀浆液中促肾上腺皮质激素释放因子（corticotropin releasing factor，CRF）含量，Western-blot法检测大鼠下丘脑中sigma-1R蛋白表达以及PKC，糖皮质激素受体（glucocorticoid receptor，GR）蛋白的磷酸化水平。结果 与正常组比较，模型组大鼠血糖含量显著升高而活动能力显著减弱（P<0.01），下丘脑中CRF含量显著升高（P<0.05）而sigma-1R的表达以及p-PKC/PKC，p-GR/GR比值显著降低（P<0.05或P<0.01）。与模型组比较，左归降糖解郁方高剂量组大鼠血糖含量显著降低（P<0.05），活动能力增强（P<0.01），下丘脑中CRF含量显著降低而sigma-1R，p-PKC/PKC，p-GR/GR显著升高（P<0.05或P<0.01）。结论 高剂量左归降糖解郁方可有效调节sigma-1R水平，并通过激活sigma-1R/PKC信号通路，降低模型大鼠下丘脑中CRF的含量，从而发挥降血糖和抗抑郁的双重作用。 |
| 关键词: 糖尿病并发抑郁症 左归降糖解郁方 下丘脑 sigma-1受体 |
| DOI：10.13748/j.cnki.issn1007-7693.2019.11.004 |
| 分类号:R965.2 |
| 基金项目:国家自然科学基金项目（81703694）；湖南省自然科学青年基金项目（2019JJ50464）；湖南省教育厅优秀青年项目（17B201）；湖南中医药大学一流学科开放基金项目（2018ZYX46） |
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| Effect of Zuogui Jiangtang Jieyu Formulation on Signaling Pathway in Hypothalamus of Diabetic Rats with Depression |
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YANG Hui1, HAN Yuanshan1, LIU Zhuo2, MENG Pan2, DU Qing3, ZHAO Hongqing2, LONG Hongping1, WANG Yuhong2,4
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1.First Affiliated Hospital, Hunan University of Chinese Medicine, Changsha 410007, China;2.Key Laboratory of Chinese Materia Medica Power and Innovation Drugs Established by Provincial and Ministry, Hunan University of Chinese Medicine, Changsha 410208, China;3.The Hunan Provincial Institute of Traditional Chinese Medicine, Changsha 410006, China;4.The Domestic First Class Construction Discipline of Chinese in Hunan University of Chinese Medicine, Changsha 410208, China
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| Abstract: |
| OBJECTIVE To investigate the effect of Zuogui Jiangtang Jieyu formulation on sigma-1 receptor/protein kinase C(sigma-1R/PKC) signaling pathway in hypothalamus of diabetic rats with depression. METHODS Animal models of diabetes complicated with depression were established and randomly divided into 4 groups:model group, positive drug group, high and low dose of Zuogui Jiangtang Jieyu formulation group(20.53, 10.26 g·kg-1). Additionally, the normal rats were belongs to the normal group. After 28 d of intragastric administration, blood glucose in each group was detected. Then the open field test was used to test the autonomic activity of rats. The pathological damage of hypothalamus was detected by HE staining in each group, and the content of corticotropin releasing factor(CRF) in hypothalamus homogenate of rats was detected by ELISA. At last, expression levels of sigma-1R, phosphorylation of PKC and glucocorticoid receptor(GR) in hypothalamus were evaluated by Western-blot. RESULTS Compared with the normal group, the blood glucose level was significantly increased and the activities were significantly decreased in model group(P<0.01). The level of CRF in hypothalamus was significantly increased(P<0.05), while the expression of sigma-1R, p-PKC/PKC, and p-GR/GR were significantly decreased(P<0.05 or P<0.01). Compared with the model group, high dose of Zuogui Jiangtang Jieyu formulation administration rescued the reduction in blood glucose(P<0.05) and improved activities(P<0.01), which in turn reduced the level of CRF in hypothalamus(P<0.05). Furthermore, the high dose of this formulation treatment also increased the expression of sigma-1R, p-PKC/PKC, and p-GR/GR(P<0.05 or P<0.01). CONCLUSION High dose of Zuogui Jiangtang Jieyu formulation can effectively regulate the expression level of sigma-1R, and reduce the content of CRF in hypothalamus by activating sigma-1R/PKC signaling pathway. The above mechanism of this formulation may be related to the effect of hypoglycemic and antidepressant. |
| Key words: diabetes mellitus with depression Zuogui Jiangtang Jieyu formulation hypothalamus sigma-1 receptor |
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