中剂量规律长期饮酒改变肠道菌群，延缓衰老，保持衰老加速模型小鼠 8 号（SAMP8）的空间记忆。

Moderate-dose Regular Lifelong Alcohol Intake Changes the Intestinal Flora, Protects against Aging, and Keeps Spatial Memory in the Senescence-accelerated Mouse Prone 8 (SAMP8) Model.

机构信息

Frontier Laboratories for Value Creation, SAPPORO HOLDINGS LTD., Japan.

出版信息

J Pharm Pharm Sci. 2016 Oct-Dec;19(4):430-447. doi: 10.18433/J3990V.

DOI:10.18433/J3990V

PMID:28057167

Abstract

PURPOSE

Heavy and long-term alcohol consumption increase the risk of alcohol-related diseases. Epidemiological studies show moderate drinking reduces the risk of mortality, cardiovascular diseases, and brain infarction in the J-shaped or U-shaped curve effect. However, why moderate drinkers may be healthy and non-drinkers may be ill in diverse populations remains controversial. Herein, we examined the relationship between moderate/lifelong alcohol intake and aging, especially aging-related cognitive functions in senescence-accelerated mouse prone 8 (SAMP8) model. Methods: SAMP8 model (5-week-old, male, n = 36), a model of age-related cognitive deficit, were group-housed (n = 6/cage) and provided free access to water (water group, n = 18) or 1% ethanol (EtOH group, n = 18, intake started when mice were 9 weeks old). The object recognition test (ORT) and object location test (OLT) were used to evaluate cognitive functions. The intestinal flora at the age of 87 weeks was analyzed by terminal restriction fragment length polymorphism (T-RFLP).

RESULTS

The lifespan of the EtOH-group mice was about 4 weeks longer than that of the water-group mice. In the EtOH group, spatial recognition impairment, assessed by OLT, was observed later (age, 73 weeks) than that in the water group (age, 52 weeks). The spinal curvature and skin conditions progressed significantly slower in the EtOH group than in the water group. Moreover, diarrhea symptoms only appeared in the water group, at the age of 82 weeks. The T-RFLP analysis of the intestinal flora indicated higher Lactobacillales order and lower Clostridium cluster XI in the EtOH group than in the water group, although those were extremely high in some mice close to death in both groups. Water-group mice with diarrhea presented significantly higher Clostridium cluster XI than did those without diarrhea (P = 0.017).

CONCLUSION

Moderate alcohol intake changes intestinal flora and positively affects aging of SAMP8 model.

摘要

目的

大量且长期饮酒会增加酒精相关疾病的风险。流行病学研究表明，适量饮酒可以降低 J 型或 U 型曲线效应下的死亡率、心血管疾病和脑梗死风险。然而，为什么在不同人群中，适量饮酒者可能健康而不饮酒者可能患病，这仍然存在争议。在此，我们研究了适度/终身饮酒与衰老的关系，特别是在衰老加速模型 8 号小鼠（SAMP8）模型中与衰老相关的认知功能。

方法

将 SAMP8 模型（雄性，5 周龄，n = 36），即与年龄相关的认知功能障碍模型，进行分组饲养（n = 6/笼），并提供自由饮用水（水组，n = 18）或 1%乙醇（乙醇组，n = 18，从 9 周龄开始摄入）。采用物体识别测试（ORT）和物体位置测试（OLT）评估认知功能。在 87 周龄时通过末端限制性片段长度多态性（T-RFLP）分析肠道菌群。

结果

乙醇组小鼠的寿命比水组小鼠长约 4 周。在乙醇组中，空间识别障碍（OLT）的评估结果较晚（73 周龄）出现，而在水组中（52 周龄）出现较早。乙醇组的脊柱弯曲和皮肤状况的进展明显比水组缓慢。此外，仅在水组中，于 82 周龄时出现腹泻症状。肠道菌群的 T-RFLP 分析表明，与水组相比，乙醇组中乳杆菌目（Lactobacillales order）较高，梭菌簇 XI（Clostridium cluster XI）较低，但两组中接近死亡的一些小鼠的肠道菌群中这两种菌的含量都极高。出现腹泻的水组小鼠的梭菌簇 XI 明显高于未出现腹泻的水组小鼠（P = 0.017）。