Abstract

Objective To explore the effect of nesfatin-1 on water intake and the mechanism of nesfatin-1 in regulating water and electrolyte balance in hypothalamus of rats. Methods Lateral ventricle implantation tube, drugs and molecular biology were used to observe the effects of exogenous and endogenous nesfatin-1 on water intake in drug causing thirsty rats and on physiological thirsty rats. Meanwhile the gene expression of NUCB2/Nesfatin-1 of water ban rats has been observed. Results Lateral ventricle injection of 150, 450 pmol exogenous nesfatin-1, the water intake in 0-120 min of rats significantly reduced (150 pmol(1.3±0.2)-(1.85±0.3)ml/100g; 450 pmol(0.8±0.4)-(1.2±0.4)ml/100g vs NS(2.5±0.3)-(3.1±0.2)ml/100g) and showed a significant dose-response relationship (P 0.05). Angiotensin II were administrated to lateral ventricle 10 min after injection of nesfatin-1. After injection of 150 pmol nesfatin-1, water intake in 15-30 min of rats significantly reduced (150 pmol(2.17±0.6)ml/100g vs NS(3.62 ±1.0)ml/100g, P 0.05). Subcutaneous injection of hypertonic saline, and water intake in rats increase rapidly(The water intake of rats with subcutaneous injection of hypertonic saline increase rapidly, while the water intake of rats with 150 pmol nesfatin-1 injection in lateral ventricle within 15~30 min and the water intake of rats with 450 pmol nesfatin-1 injection in lateral ventricle within 120 min significantly reduced. Lateral ventricle injection of 150 or 450 pmol nesfatin-1, water intake of each time period within 60 min in rats significantly reduced (150 pmol : (0.25±0.2)-(1.6±0.25)ml/100g; 450 pmol(0.1±0.15)-(1.92±0.2)ml/100g vs NS(0.9±0.2)-(2.9±0.2)ml/100g , P 0.05). Three hours After the second time hypothalamus PVN injection of antisense RNA nesfatin-1, angiotensin II (50 pmol/2 mul) were given and water intake in rats increased significantly (Antisense nesfatin-1(1.87±0.4)-(2.77±0.6)ml/100g vs NS(0.72±0.1)-(1.17±0.4)ml/100g , P 0.05). NUCB2 gene expression was significantly reduced in the hypothalamus (water ban: (-7.2±1.1)% vs free drinking water: (0.82±0.4)%, P<0.01) in rats after 18 hours water ban; The hypothalamus NUCB2 gene expression had a significant rise (water supply restore: (8.1±1.1)% vs free drinking water: (0.82±0.4)%, P<0.01) in rats with water supply restore. Conclusion Nesfatin-1 involves in the regulation of water intake in physiology or drug causing thirsty. Nesfatin-1 plays an important role in the hypothalamus to regulate water-electrolyte balance and thirsty mechanisms. Key words: Nesfatin-1; Drinking behaviour; Angiotensin II; Rat

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