【摘要】 目的 探讨不同成分短链脂肪酸（short-chain fatty acids,SCFAs）对慢性不可预测温和应激（chronic unpredictable mild stress,CUMS）模型大鼠抑郁样行为及肠道菌群的影响。方法 76只雄性成年大鼠随机分为乙酸钠干预组（n=12）、丙酸钠干预组（n=15）、丁酸钠干预组（n=14）、短链脂肪酸混合物干预组（n=12）、模型组（n=13）、对照组（n=10）。除了对照组，其他组均采用CUMS进行抑郁造模，且在每日造模前连续干预。乙酸组、丙酸组、丁酸组按体质量1 mL/100 g分别腹腔注射50 mg/kg乙酸钠溶液、100 mg/kg丙酸钠溶液、50 mg/kg丁酸钠溶液；混合物组按体质量1 mL/100 g腹腔注射1∶1∶1的乙酸钠、丙酸钠、丁酸钠混合溶液；模型组按体质量1 mL/100 g腹腔注射生理盐水，干预组每日应激前给药，持续28 d。通过糖水偏好、强迫游泳及旷场实验评估大鼠行为；采集盲肠粪便样本，用16S rRNA测序分析肠道菌群组成。结果 与对照组相比，模型组大鼠体质量下降，糖水偏好系数降低，不动时间延长（P<0.05），丁酸组逆转了糖水偏好系数、不动时间的改变（P<0.05），混合物组提高了糖水偏好系数（P<0.05）。与对照组比，模型组大鼠独有的物种数量减少且肠道群落结构发生改变；干预后乙酸组、丙酸组、丁酸组、混合物组独有的物种数量均升高且乙酸组肠道群落结构得到部分改善。LEfSe分析发现双歧杆菌属（Bifidobacterium）在丙酸组中富集，柯林斯菌属（Collinsella）在混合物组中富集。结论 丁酸钠能明显改善大鼠的抑郁样行为，乙酸钠、丙酸钠、短链脂肪酸混合物会影响肠道菌群组成，但抗抑郁效果不明显。丁酸钠可能是一种补充短链脂肪酸干预抑郁症的更有效的选择。更多还原

【Abstract】 Objective To investigate the effects of different components of short-chain fatty acids(SCFAs) on depression-like behaviors and intestinal flora in chronic unpredictable mild stress(CUMS)-induced depressive rats.Methods Seventy-six healthy male rats were randomly divided into six groups. Rats in the acetate group(n=12),propionate group(n=15) and butyrate group(n=14) were given intraperitoneal injection(i.p.) of 50 mg/kg sodium acetate,100 mg/kg sodium propionate and 50 mg/kg sodium butyrate, respectively. Rats in the SCFAs group(n=12) were given i.p of 1∶1∶1 sodium acetate, sodium propionate and sodium butyrate mixed solution. Rats in the CUMS group(n=13) were given i.p of 1 mL/100 g saline. Rats in the control group(n=10) did not receive any treatment. Besides the control group, other groups were subjected to CUMS and intraperitoneal injection before stress for 28 days. The depression-like behaviors were assessed by sucrose preference test, forced swimming test, open field test, and then cecal fecal samples were collected to examine the composition of intestinal flora by 16S rRNA sequencing. Results Compared with the control group, the body weight of rats and the sugar preference coefficient decreased and the immobility time increased in the CUMS group(P<0.05). The butyrate group reversed the alterations in change of the sugar preference coefficient and the immobility time(P<0.05). Additionally, the sugar preference coefficient was elevated in the SCFAs group(P<0.05). The community structure of intestinal flora was changed in the CUMS group compared to the control group and was partially improved in the acetate group. The number of unique species reduced in the CUMS group but increased in the acetate group, propionate group,butyrate group and SCFAs group. LEfSe found the enrichment of Bifidobacterium in the propionate group and the enrichment of Collinsella in the SCFAs group. Conclusions Sodium butyrate significantly improves depressive-like behaviors of the CUMS-induced rats. Sodium acetate, sodium propionate, and short-chain fatty acid mixture can influence the composition of intestinal flora. However, their antidepressant effect is not significant. Sodium butyrate may be a better alternative for supplementing short-chain fatty acids in depression.更多还原