慢性应激模型大鼠体重、摄食变化与粪便代谢物的相关性研究

目的:探讨慢性应激导致大鼠体重增长缓慢、摄食量下降与粪便代谢物变化的相关性。方法:48只健康雄性SD大鼠,随机分为正常组和慢性束缚应激组。慢性束缚应激组大鼠每天给予束缚应激3 h,连续21 d;正常组大鼠正常饲养21 d,不予应激。观测2组大鼠旷场实验和高架十字迷宫实验行为学指标变化及糖水偏好率、血清D-木糖含量和小肠炭末推进率,采用~1H-NMR代谢组学技术检测大鼠粪样代谢物,Pearson相关分析探究应激大鼠体重、摄食量变化与上述观测指标的关系。结果:与正常组大鼠比较,慢性束缚应激组大鼠体重增长缓慢,摄食量显著下降(P<0.01),5 min内在旷场内总移动距离和中央区移动距离均显著减少(P<0.01),内高架十字迷宫实验中5 min内在开放臂停留时间显著缩短(P<0.01)。束缚应激21 d大鼠血清D-木糖含量和糖水偏好率均较正常大鼠显著下降(P<0.05)。小肠炭末推进率在两组间比较差异无统计学显著性(P>0.05)。粪样代谢组学检测获得乙酸盐、丁酸盐、葡萄糖、丙酸盐、谷氨酸盐、核糖、庚二酸盐、乳酸盐、丙氨酸和戊酸盐10种差异代谢物,且慢性束缚应激组大鼠粪样中含量显著高于正常组大鼠(P<0.05)。Pearson相关分析提示应激21 d大鼠摄食量与差异代谢物乙酸盐和庚二酸盐呈显著负相关(P<0.05),体重变化与上述指标均无显著相关性。结论:慢性束缚应激大鼠粪便小分子代谢产物乙酸盐和庚二酸盐与其摄食量存在一定相关性,但具体代谢通路有待进一步研究。

Correlation between fecal metabolites and body weight/food intake in rats after chronic immobilization stress

AIM: To explore the correlation between fecal metabolites and body weight/food intake in rats after chronic immobilization stress(CIS). METHODS: Healthy male Sprague-Dawley(SD) rats(n=48) were randomly divided into control group and CIS group. The rats in CIS group were subjected to 3 h of immobilization stress a day for 21 consecutive days, and the rats in control group were kept for 21 d without stress intervention. The behaviors in open-field test(OFT) and elevated plus-maze test(EPM test), the sucrose consumption, the serum D-xylose content, and the small bowel transit rate were detected. The fecal metabolites were determined by ~1H-nuclear magnetic resonance spectroscopy(~1H-NMR) technique, and differential metabolites in the rats of 2 groups were analyzed by multivariate statistics. The correlation between body weight/food intake and above indexes of CIS rats were observed by Pearson correlation analysis. RESULTS: Compared with the control rats, the body weight of CIS rats was increased slowly and the food intake was decreased significantly(P<0.01). In the OFT, both the total and central distance covered in CIS rats were reduced significantly than those in control group within 5 min(P<0.01). In the EPM test, the residence time in open-arms of CIS rats within 5 min was shortened dramatically than those in the control group(P<0.01). The content of serum D-xylose and the sucrose consumption of the rats after stress for 21 d were decreased markedly(P<0.05). The small bowel transit rate of CIS rats was lower than that of control rats, but no statistical difference was observed(P>0.05). Acetate, butyrate, glucose, propionate, glutamate, ribose, pimelate, lactate, alanine, valerate, total 10 kinds of differential metabolites in fecal samples were detected, and the 10 kinds of metabolites in CIS rats were higher than that of the control rats(P<0.05). Pearson correlation analysis showed that food intake of CIS rats was negatively correlated with metabolites of acetate and pimelate(P<0.05), and no correlation between body weight and above indexes was found. CONCLUSION: Under the CIS condition, there are certain correlations between food intake and metabolites of acetate and pimelate, but the mechanism still need further study.