CNP signal pathway up-regulated in rectum of depressed rats and the interventional effect of Xiaoyaosan

CNP signal pathway up-regulated in rectum of depressed rats and the interventional effect of Xiaoyaosan
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DOI:
10.3748/wjg.v21.i5.1518
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发表时间:
2015-02-07
影响因子:
4.3
通讯作者:
Guo, Hui-Shu
Guo, Hui-Shu
中科院分区:
医学2区
文献类型:
--
作者:
Li, Ping;Tang, Xu-Dong;Guo, Hui-Shu

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目的:目的观察C型利钠肽(CNP)/利钠肽受体B(NPR-B)在抑郁模型大鼠直肠的分布和表达,以及逍遥散的干预作用(200 ± 20 g)分为5组:对照组、抑郁模型组、小剂量组、中剂量组、大剂量组。动物实验持续3 wk。主要对照组动物自由进食。所有其他组的大鼠单独饲养,每天暴露于经典的慢性轻度不可预测的刺激。XYS组于刺激前1h分别灌胃XYS低、中、高剂量组。原代对照组和抑郁模型组灌胃生理盐水,灌胃条件同XYS组。3周后处死大鼠,采用免疫组化、实时荧光定量PCR和Western blotting方法检测大鼠直肠组织中CNP和NPR-B的表达水平。抑郁模型组CNP和NPR-B基因和蛋白表达水平均显著高于原代对照组(n = 9; P < 0.01)。XYS干预可显著抑制抑郁大鼠CNP和NPR-B的表达水平。高剂量XYS组中CNP和NPR-B的表达水平与主要对照组中的表达水平无显著差异。与模型对照组相比,高、中剂量组大鼠直肠组织中CNP和NPR-B表达水平显著降低(n = 9; P < 0.01)。结论:抑郁大鼠直肠组织中CNP/NPR-B通路表达上调,可能是抑郁相关消化系统疾病的发病机制之一。XYS至少部分拮抗该途径。
AIM: To investigate the distribution and expression of C-type natriuretic peptide (CNP)/natriuretic peptide receptor B (NPR-B) in the rectum of a rodent depression model and the interventional effect of Xiaoyaosan (XYS).METHODS: Male rats (n = 45) of clean grade (200 +/- 20 g) were divided into five groups after one week of adaptive feeding: primary control, depression model, low dose XYS, middle dose XYS, and high dose XYS. The animal experiment continued for 3 wk. Primary controls were fed normally ad libitum. The rats of all other groups were raised in solitary and exposed to classic chronic mild unpredictable stimulation each day. XYS groups were perfused intragastrically with low dose, middle dose, and high dose XYS one hour before stimulation. Primary control and depression model groups were perfused intragastrically with normal saline under similar conditions as the XYS groups. Three weeks later, all rats were sacrificed, and the expression levels of CNP and NPR-B in rectum tissues were analyzed by immunohistochemistry, real-time polymerase chain reaction, and Western blotting.RESULTS: CNP and NPR-B were both expressed in the rectum tissues of all rats. However, the expression levels of CNP and NPR-B at both gene and protein levels in the depression model group were significantly higher when compared to the primary control group (n = 9; P < 0.01). XYS intervention markedly inhibited the expression levels of CNP and NPR-B in depressed rats. The expression levels of CNP and NPR-B in the high dose XYS group did not significantly differ from the expression levels in the primary control group. Additionally, the high and middle dose XYS groups (but not the low dose group) significantly exhibited lower CNP and NPR-B expression levels in the rectum tissues of the respectively treated rats compared to the untreated depression model cohort (n = 9; P < 0.01).CONCLUSION: The CNP/NPR-B pathway is upregulated in the rectum of depressed rats and may be one mechanism for depression-associated digestive disorders. XYS antagonizes this pathway at least partially.