健康与遗传心理学研究室知识库

【研究背景】抑郁是世界上最常见的精神疾病，影响着3 亿5 千万人的健康和生命，带来了最大的医疗疾病负担，占总负担10.3%。但是目前抑郁的具体病理生理机制仍不确定，传统假说如神经递质缺乏理论、神经营养因子理论、神经内分泌理论和细胞因子理论都只能解释抑郁的部分生理机制，在部分患者中得到验证，无法获得一致认同；而考虑了肠道微生物作用的新理论如卫生假说和肠漏理论还正在发展中。对于抑郁的预防，应激性生活事件和易感基因仍是公认的风险因素，但这些因素如何致病还并不确定。在已有的治疗中，目前常用的抗抑郁药物仍然是针对脑神经递质，如一线抗抑郁药选择性五羟色胺重吸收抑制剂（SSRI），但这些药物对相当数量的患者没有效果。而由于社会经济文化等原因，仍有大部分患者无法得到帮助。因此，目前阐明抑郁的发病机制，开发更加经济有效的治疗方法，已经迫在眉睫。

【研究目的】肠道微生物可通过微生物-肠-脑轴影响宿主的生理和心理健康，本研究希望通过研究抑郁模型中大鼠的行为和生理异常及伴随着的肠道微生物改变，探索肠道微生物在抑郁发生中的作用，并针对肠道微生物通过有效益生菌进行干预，检验能否通过调节肠道微生物治疗抑郁，从而阐明抑郁与肠道微生物的关系，开发新的抑郁治疗方法。

【研究方法】本研究使用两种大鼠抑郁模型，从环境和遗传两个方面探索了肠道微生物在抑郁中的作用及针对肠道微生物补充瑞士乳杆菌NS8 的治疗效果。对于外界环境引起的抑郁，我们采用了SD 大鼠慢性束缚应激模型，比较了模型组大鼠与对照组大鼠的行为认知、生理及菌群差异，并检测了补充瑞士乳杆菌NS8对这三个方面的影响，探索瑞士乳杆菌NS8 干预对于后天环境风险引发抑郁的治疗效果及作用机制。对于遗传因素引起的抑郁，我们选择了遗传易感的WKY大鼠模型，比较了WKY 大鼠与其来源品系Wistar 大鼠和行为实验常用SD 大鼠的行为、生理和菌群差别，检测了补充瑞士乳杆菌NS8 对这三个方面的影响，探索瑞士乳杆菌NS8 干预对于先天遗传风险引发抑郁的治疗效果及作用机制。通过研究这两个模型中肠道微生物的变化和瑞士乳杆菌NS8 干预的效果，来分析……

Backgroud: Depression is the most common mental disease in the world. More than 350,000,000 people have been sufferring from it according to the World Health Organization. Depression is responsible for 10.3% of the total ‘years lost’ to disability,which is more than any other diseases. But the physiopathologic mechanism of depression is still unclear. Conventional theories in depression like neurotransmitters defienciey hypothesis, neurotrophic factors hypothesis, neuroendocrine hypothesis and cytokine hypothesis have all explained partial of depression, and neither of them acquire concordant identification. While new theories involving the gut microbiota like hygiene hypothesis and leaky gut theory have been still developing. Stessful life events and susceptible genes are widly recognized as risk factors for depression. And the most popular target of current depression intervention is to restore the neurotransmitters content in the brain, like using the first-line antidepressant selective serotonin reuptake inhibitor (SSRI) to increase 5-HT content. But there are still more than half of patients who cannot get help from current therapies. Thus make clear the mechanisms of depression and developing new effective therapies are in extremely urgent.

Objetive: The gut bacteria can influence host physiological and mental health through the microbiota-gut-brain axis. The present research was aimed to find the behaviors,biomarkers and gut microbiota abnormalities in different rat depression models,explore the effects gut microbiota make, test whether using some potential effective probiotics to regulate gut microbiota alleviate depression or not, clarify the relationship between depression and gut microbiota and how probiotic intervention works.Methods: We selected two depression model and measured the effects of Lactobacillus helveticus NS8 intervention targeting the gut microbiota from both environmental and genetic factors. For the depression induced by environmental factors, we selected chronic restraint stress model in SD rats, compared the behavioral, physiological and gut microbiota differences between model group and control group,tested the influence of Lactobacillus helveticus NS8 intervention on all the three aspects, and explored the effects of Lactobacillus helveticus NS8 supplementation on stress related depression and how it worked. For genetic susceptible depression, we used WKY rat model, compared the behavioral, physiological and gut microbiotal differences between WKY rat and it, s original strain Wistar rat and the most commonly used SD rat, measured the impaction of Lactobacillus helveticus NS8 supplimention on all the three aspects, and studied the effects of Lactobacillus helveticus NS8 intervention on genetic susceptibile depression and how it worked……