海马BDNF和iNOS与慢性应激性抑郁的关系

Sequental Involvement of Hippocampal BDNF and Inducible Nitric Oxide in Depression Induced by Chronic Unpredicted Mild Stress

建立慢性不可预见性抑郁动物模型,采用液体消耗实验(fluid consumption test,FCT)、敞箱实验(Open field test,OFT)和强迫游泳(Forced swimming test,FST)等方法进行行为学测试,并用免疫组织化学的方法检测海马BDNF和iNOS的表达,运用腹腔注射药物的方法探索BDNF和iNOS的作用与关系.探讨了海马脑源性神经营养因子(BDNF)和诱导型一氧化氮合酶(iNOS)在慢性应激诱导的抑郁症中的关系,及抑郁症的发病机制.与对照组相比,慢性不可预见性应激(Chronic unpredicted mild stress,CUMS)组大鼠的行为学表现能力下降,BDNF表达下降(n=8,P<0.01),iNOS的表达升高(n=8,P<0.01);阻断内源性BDNF大鼠的行为学表现能力也下降,iNOS的表达升高(n=7,P<0.01);而海马微量注射iNOS的抑制剂SMT均可反转CUMS和BDNF抑制剂所导致的行为学表现能力下降的现象.慢性不可预见性应激引起海马BDNF表达下降,NO过高而导致抑郁.BDNF对神经元具有保护作用,BDNF的抗抑郁作用可能是通过抑制iNOS的表达而起作用的.提示BDNF等神经保护因子通过抑制iNOS的过量表达而保护脑组织可能是治疗抑郁症的一个重要途径.

The rat model of depression was established by exposing to an unpredictable sequence of stressors. By means of fluid consumption test, forced swimming test and open file test, the behaviors of the animals were determined, and the expression of brain derived neurotrophic factor （BDNF） and neuron Nitric-oxide Synthase（iNOS） . And in rat hippocampal were observed. The effects of chronic and unpredictable stress on the pathological changes and expression of iNOS and BDNF of rat hippocampal and behavioral changes were observed. Compared with the control group rats, the behavioural ability of the CUMS group rats was significantly depressed, and the expression of kalirin significantly decreased （ n = 8, P 〈 0. 01 ）, but the expression of iNOS significantly increased （ n = 8, P 〈 0. 01 ） ; Compared with the control group rats, the behavioural ability of the k252a group rats was significantly depressed, and the expression of iNOS and significantly increased（ n = 7 ,P 〈 0. 05） ; Compared with the CUMS group rats, the behavioural ability of the SMT ＋ CUMS group and SMT ＋ K252a group rats was significantly depressed. BDNF protect neurons from apoptosis and consequently played the antidepressive role, the antidepressive effect of BDNF may be through inhibiting the expression of iNOS. It is revealed that Neuroprotective factors like BDNF which inhibit the overexpression of iNOS and consequently protect the brain tissue should become the new treatment targets of depression.