目的 觀察氨磺必利對(duì)抑郁癥大鼠行為的影響，并探究其對(duì)大鼠海馬組織Toll樣受體（TLR）/NOD樣受體（NLR）通路相關(guān)蛋白表達(dá)的影響。方法 將SD大鼠隨機(jī)分為對(duì)照組、模型組及低、中、高劑量（0.3、1.2、4.8 g/kg）氨磺必利組，每組10只，除對(duì)照組外，其他各組大鼠給予8周慢性溫和不可預(yù)知應(yīng)激（CUMS）刺激制備抑郁癥大鼠模型，于造模第7~8周，低、中、高劑量氨磺必利組分別ig給予0.3、1.2、4.8 g/kg氨磺必利溶液，對(duì)照組、模型組ig等量生理鹽水，給藥體積10 mL/kg，分別于造模后（CUMS 6周）、給藥后（CUMS 8周）采用糖水偏好、強(qiáng)迫游泳、懸尾及曠場(chǎng)實(shí)驗(yàn)評(píng)估大鼠行為；實(shí)驗(yàn)結(jié)束后，取各組大鼠海馬組織，Werstern blotting法檢測(cè)TLR2、NLRP1、NLRP3、ASC、TLR4及Caspase-1蛋白表達(dá)情況，ELISA法檢測(cè)白細(xì)胞介素（IL）-6、IL-1β、IL-18水平。結(jié)果 造模后，相較于對(duì)照組，模型組及低、中、高劑量氨磺必利組大鼠體質(zhì)量、糖水偏好指數(shù)、曠場(chǎng)中活動(dòng)距離及站立次數(shù)降低，強(qiáng)迫游泳及懸尾靜止時(shí)間延長(zhǎng)（P<0.05）。相較于造模后，給藥后模型組大鼠體質(zhì)量、糖分偏好指數(shù)、曠場(chǎng)中活動(dòng)距離及站立次數(shù)降低，強(qiáng)迫游泳及懸尾靜止時(shí)間延長(zhǎng)（P<0.05）；低、中、高劑量氨磺必利組大鼠體質(zhì)量、糖分偏好指數(shù)、曠場(chǎng)中活動(dòng)距離及站立次數(shù)增加，強(qiáng)迫游泳及懸尾靜止時(shí)間縮短（P<0.05）。給藥后，相較于對(duì)照組，模型組及低、中、高劑量氨磺必利組大鼠體質(zhì)量、糖分偏好指數(shù)、曠場(chǎng)中活動(dòng)距離及站立次數(shù)降低（P<0.05），強(qiáng)迫游泳及懸尾靜止時(shí)間延長(zhǎng)（P<0.05），海馬中TLR2、TLR4、NLRP1、NLRP3、ASC、Caspase-1蛋白表達(dá)及IL-6、IL-1β、IL-18水平均增高（P<0.05）；相較于模型組，低、中、高劑量氨磺必利組大鼠體質(zhì)量、糖分偏好指數(shù)、曠場(chǎng)中活動(dòng)距離及站立次數(shù)增加，且低、中劑量組依次增加，均高于高劑量氨磺必利組（P<0.05），強(qiáng)迫游泳及懸尾靜止時(shí)間縮短，且低、中劑量組依次縮短，均短于高劑量氨磺必利組（P<0.05），海馬中TLR2、TLR4、NLRP1、NLRP3、ASC、Caspase-1蛋白表達(dá)及IL-6、IL-1β、IL-18水平均降低，且低、中劑量組依次降低，均低于高劑量氨磺必利組（P<0.05）。結(jié)論 低劑量氨磺必利可降低抑郁模型大鼠海馬中TLR/NLR通路相關(guān)蛋白表達(dá)量，抑制下游炎性因子釋放，從而改善CUMS誘導(dǎo)的大鼠抑郁樣行為。

Objective To observe the effect of amisulpride on the behavior of depression rats, and to explore the effect of amisulpride on the expression of Toll like receptor (TLR)/NOD like receptor (NLR) pathway related proteins in the hippocampus of rats. Methods SD rats were randomly divided into control group, model group, and low, medium and high dose (0.3, 1.2, 4.8 g/kg) amisulpride groups, except the control group, rats in the other group were given chronic unpredictable mild stress (CUMS) for 8 weeks to prepare depression rats model. At 7th-8th weeks, rats in the low, medium and high dose amisulpride groups were administrated with 0.3, 1.2, 4.8 g/kg amisulpride solutions by ig respectively, rats in the control group and model group were administrated with normal saline by ig, with volume of 10 mL/d. Sugar preference, forced swimming, tail suspension and open field experiments were used to evaluate the behavior of rats after modeling (6 weeks after CUMS) and after administration (8 weeks after CUMS); at the end of the above experiments, the hippocampus of rats were taken, and the expressions of TLR2, NLRP1, NLRP3, ASC, TLR4 and Caspase-1 proteins were detected by Werstern blotting, and the levels of IL-6, IL-1 β and IL-18 were detected by ELISA. Results After molding, compared with those in the control group, the body weight, sugar preference index, open field activity distance and standing times of rats in model group, the low, medium and high dose amisulpride groups were lower, forced swimming time and tail suspension time were longer(P<0.05). Compared with those after molding, body weight, sugar preference index, activity distance and standing times in open field of rats in model group after administration were lower, forced swimming and tail suspension time were longer (P<0.05); body weight, sugar preference index, activity distance and standing times in open field of rats in the low, middle and high dose amisulpride groups after administration were higher, forced swimming and tail suspension time were shorter (P<0.05). After administration, compared with those in the control group, body weight, sugar preference index, open field activity distance and standing times of rats in model group and low, medium and high dose amisulpride groups were lower (P<0.05), forced swimming and tail suspension time were longer (P<0.05), the expressions of TLR2, TLR4, NLRP1, NLRP3, ASC, Caspase-1 proteins and the levels of IL-6, IL-1 β, IL-18 in hippocampus were all higher (P<0.05); compared with those in the model group, the body weight, sugar preference index, open field activity distance and standing times of rats in the low, middle and high dose group were higher, and those in the low and middle dose groups increased in turn, which were higher than those in the high dose group (P<0.05), the time of forced swimming and tail suspension were shortened, and those in the low and middle dose groups were shorter than those in the high dose group (P<0.05), the expressions of TLR2, TLR4, NLRP1, NLRP3, ASC, Caspase-1 and the levels of IL-6, IL-1 β, IL-18 in hippocampus were all lower, and those in the low and middle dose groups were lower than those in the high dose group (P<0.05). Conclusion Low dose of sulfabilide can reduce the expression of TLR/NLR pathway related protein in hippocampus, inhibit the release of downstream inflammatory factors, and improve the depression like behavior of rats induced by CUMS.

R964

國(guó)家重點(diǎn)研發(fā)計(jì)劃中醫(yī)現(xiàn)代化研究重點(diǎn)（聯(lián)合合作）專項(xiàng)（2018YFC1705801）