目的 探究酸棗仁湯對(duì)創(chuàng)傷后應(yīng)激障礙（PTSD）模型小鼠行為學(xué)的影響及機(jī)制。方法 除對(duì)照組外，其余小鼠采用單次延長應(yīng)激和足部電擊（SPS&S）建立PTSD模型，造模結(jié)束后隨機(jī)分為5組：模型組及酸棗仁湯低、中、高劑量（3、6、12 g·kg^-1）組和鹽酸帕羅西?。?.01 g·kg^-1）組，每組8只，對(duì)照組和模型組給予等體積蒸餾水，連續(xù)ig 14 d。末次給藥結(jié)束后，進(jìn)行行為學(xué)檢測(cè)；蘇木精-伊紅（HE）染色法觀察小鼠海馬組織病理變化；免疫熒光染色法檢測(cè)海馬小膠質(zhì)細(xì)胞標(biāo)志物Iba-1熒光強(qiáng)度；ELISA法檢測(cè)小鼠血清腫瘤壞死因子-α（TNF-α）、白細(xì)胞介素-6（IL-6）、皮質(zhì)酮（CORT）及海馬組織中TNF-α、IL-6、CORT、5-羥色胺（5-HT）、腦源性神經(jīng)影響因子（BDNF）含量；Western blotting法檢測(cè)小鼠海馬Janus蛋白酪氨酸激酶2（JAK2）、磷酸化Janus蛋白酪氨酸激酶2（p-JAK2）、信號(hào)轉(zhuǎn)導(dǎo)因子和轉(zhuǎn)錄激活因子3（STAT3）、磷酸化信號(hào)轉(zhuǎn)導(dǎo)因子和轉(zhuǎn)錄激活因子3（p-STAT3）、細(xì)胞外調(diào)節(jié)蛋白激酶（ERK1/2）、磷酸化細(xì)胞外調(diào)節(jié)蛋白激酶（p-ERK1/2）、環(huán)腺苷酸效應(yīng)元件結(jié)合蛋白（CREB）、磷酸化環(huán)腺苷酸效應(yīng)元件結(jié)合蛋白（p-CREB）蛋白的表達(dá)。結(jié)果 與對(duì)照組比較，模型組小鼠在恐懼消退實(shí)驗(yàn)中凝滯時(shí)間顯著延長（P＜0.01）、曠場(chǎng)實(shí)驗(yàn)中央?yún)^(qū)域運(yùn)動(dòng)路程和滯留時(shí)間明顯減少（P＜0.01）、高架十字迷宮實(shí)驗(yàn)中進(jìn)入開放臂次數(shù)和停留時(shí)間縮短（P＜0.01），強(qiáng)迫游泳不動(dòng)時(shí)間顯著增加（P<0.01），提示模型制備成功；海馬神經(jīng)元明顯損傷；海馬CA1區(qū)Iba-1熒光強(qiáng)度增強(qiáng)；小鼠血清TNF-α、IL-6、CORT含量顯著升高（P＜0.05、0.01），海馬TNF-α、IL-6、CORT含量顯著升高（P＜0.05），5-HT、BDNF含量顯著降低（P＜0.05、0.01）；p-JAK2、p-STAT3蛋白表達(dá)顯著升高（P＜0.05），p-ERK1/2、p-CREB蛋白表達(dá)顯著降低（P＜0.05）；與模型組相比，酸棗仁湯和鹽酸帕羅西汀治療后能夠明顯改善上述行為學(xué)指標(biāo)（P＜0.05、0.01）；改善海馬神經(jīng)元細(xì)胞損傷；海馬CA1區(qū)Iba-1熒光強(qiáng)度增強(qiáng)；降低小鼠血清TNF-α、IL-6、CORT含量（P＜0.05、0.01），升高海馬組織中5-HT、BDNF含量（P＜0.05、0.01）；顯著降低p-JAK2、p-STAT3蛋白表達(dá)（P＜0.05、0.01），顯著升高p-ERK1/2、p-CREB蛋白表達(dá)（P＜0.05、0.01）。結(jié)論 酸棗仁湯能夠明顯改善PTSD小鼠的恐懼、焦慮、抑郁樣行為，其機(jī)制可能與調(diào)控JAK2/STAT3、ERK1/2/CREB通路、改善神經(jīng)炎癥、調(diào)節(jié)下丘腦-垂體-腎上腺軸（HPA）軸紊亂、增加5-HT、BDNF含量有關(guān)。

Objective To explore effects and mechanisms of Suanzaoren Decoction on behavior of mice with post-traumatic stress disorder (PTSD) model. Methods Except for the control group, the rest of the mice were subjected to a single prolonged stress and foot shock (SPS&S) to establish the PTSD model. After the model was established, the mice were randomly divided into five groups: model group and Suanzaoren Decoction low, medium, and high dose (3, 6, and 12 g·kg^-1) groups and paroxetine hydrochloride (0.01 g·kg^-1), with eight mice in each group. The control group and the model group were given an equal volume of distilled water, and the mice in each group were administered with the respective treatments by ig for 14 consecutive days. After the last delivery, behavioral tests, hematoxylin-eosin (HE) staining were used to observe the mice hippocampal tissue pathological changes; Immunofluorescence staining was used to detect the fluorescence intensity of hippocampal microglia marker Iba-1; ELISA method was used to detect the mice serum TNF-α, IL-6, CORT and TNF-α, IL-6, CORT, 5-HT, BDNF levels in the hippocampus; The protein expressions of JAK2, p-JAK2, STAT3, p-STAT3, ERK1/2, p-ERK1/2, CREB and p-CREB in hippocampus were detected by Western blotting. Results Compared with the blank group, the mice in the model group showed significantly prolonged stagnation time in the fear extinction test (P <0.01), significantly reduced distance and retention time in the central area of the open field test (P <0.01), significantly shortened number of entry into the open arm and residence time in the elevated plus maze test (P <0.01), and significantly increased forced swimming immobility time (P <0.01). Tip model preparation of success. The hippocampal neurons were obviously damaged, the fluorescence intensity of Iba-1 in CA1 region of hippocampus was increased. The contents of serum TNF-α, IL-6 and CORT in the mice were significantly increased (P <0.05, 0.01), and the contents of hippocampal TNF-α, IL- 6 and CORT were significantly increased (P <0.05), while the contents of 5-HT and BDNF were significantly decreased (P <0.05, 0.01). p-JAK2, p-STAT3 protein expression was significantly increased (P <0.05), p-ERK1/2, p-CREB protein expression decreased significantly (P <0.05); Compared with model group, Suanzaoren Decoction and paroxetine hydrochloride after treatment could obviously improve the behavior (P <0.05, 0.01), improve hippocampal neurons in mice, decrease the fluorescence intensity of Iba-1 in CA1 region of hippocampus, decrease the levels of TNF-α, IL-6 and CORT in serum (P <0.05, 0.01), and increase the levels of 5- HT and BDNF in hippocampus (P <0.05, 0.01), reduce p-JAK2, p-STAT3 protein expression significantly (P <0.05, 0.01), increase p-ERK1/2, p-CREB protein expression significantly (P <0.05, 0.01). Conclusion Suanzaoren Decoction can significantly improve the fear, anxiety, and depression-like behaviors of PTSD mice, and its mechanism may be related to regulating the JAK2/STAT3, ERK1/2/CREB pathways, improve nerve inflammation, adjusting HPA axis disorders, increase content of 5-HT, BDNF.

國家自然科學(xué)基金項(xiàng)目（82304504）;陜西省高水平中醫(yī)藥重點(diǎn)學(xué)科-中藥藥理學(xué)