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目的:探讨外源性给予脑源性神经营养因子前体(brain-derived neurotrophic factor precursor，proBDNF)后脑卒中后抑郁(post-stroke depression，PSD)大鼠额前皮质凋亡信号通路蛋白的表达变化。方法:在55只健康成年雌性SD大鼠中，随机选取25只作为PSD组，其余30只随机分为正常组、抑郁组、卒中组，每组10只。卒中组采用线栓法建立大脑中动脉栓塞模型；抑郁组采用慢性不可预见性温和应激(chronic unpredictable mild stress，CUMS)结合孤养法制备大鼠慢性应激抑郁模型；PSD组采用线栓法建立MCAO模型，术后1周加以CUMS及孤养法制备PSD模型；PSD组大鼠造模后2周，随机选取15只进行侧脑室埋管，并随机分为proBDNF组、组织型纤溶酶原激活剂组(tPA组)和NS组，埋管后1周进行侧脑室注射tPA、ProBDNF，连续给药1周。于造模后第4周及第8周末采用Western blot检测各组大鼠额前皮质c-Jun氨基末端激酶(c-Jun N-terminal kinase，JNK)、p-JNK、p53、p-p53、Bax蛋白表达。采用SPSS 17.0进行数据分析，组间比较采用单因素方差分析，采用SNK-n q进行两两比较。n 结果:大鼠MCAO造模第4周末和第8周末，正常组、抑郁组、卒中组和PSD组大鼠额前皮质p-p53、p53、p-JNK、JNK和Bax表达均差异有统计学意义(n F＝3.426~90.355，均n P<0.05)。事后两两比较结果显示，相比正常组，在第4周末，PSD大鼠额前皮质p-JNK(0.378±0.042)、Bax(0.478±0.054)蛋白的表达均升高(均n P<0.05)；在第8周末，PSD组大鼠额前皮质中p-JNK(0.411±0.056)、p-p53(0.286±0.083)、Bax(0.471±0.008)蛋白表达均升高(均n P<0.05)。予侧脑室注射proBDNF后，proBDNF组、tPA组和NS组p-p53、p53、p-JNK、JNK和Bax表达差异有统计学意义(n F＝16.915~287.039，均n P<0.01)。事后两两比较结果显示，相比NS组，proBDNF组大鼠额前皮质p-JNK(0.35±0.01)、p-p53(0.31±0.01)的表达显著增加(均n P<0.05)。予侧脑室注射proBDNF后，proBDNF组、tPA组和NS组大鼠体质量、蔗糖偏好率、水平运动距离和垂直运动距离均差异有统计学意义(n F＝18.741~76.305，均n P<0.01)，与NS组和tPA组相比，proBDNF组行为学指标[体质量(224.36±3.23)g、蔗糖偏好率(69.83±1.72)%、水平运动距离(57.93±2.09)格、垂直运动距离(19.79±1.81)次]均显著下降(均n P<0.05)。n 结论:proBDNF促进了PSD大鼠凋亡信号通路的激活。“,”Objective:To observe the changes of protein expression of apoptosis signal pathway in prefrontal cortex of rats with post-stroke depression(PSD) after lateral ventricle injected of brain-derived neurotrophic factor precursor(proBDNF).Methods:Among 55 healthy adult female SD rats, 25 rats were randomly selected as PSD group, and the other 30 rats were randomly divided into normal group (n n=10), depression group (n n=10) and stroke group (n n=10). The middle cerebral artery occlusion(MCAO) model was established by thread occlusion in the stroke group, the chronic stress depression model in the depression group was established by the combination of chronic unpredictable mild stress(CUMS) and the solitary feeding method.And the rats in the PSD group were established MCAO model first, then they were received CUMS stress and solitary rearing one week later so as to establish PSD model.Two weeks after the establishment of the model, 15 rats in PSD group were randomly divided into proBDNF group, rats in tPA group and NS control group.One week after buried tube of lateral ventricle, rats in tPA and proBDNF were injected into the lateral ventricle for one week.The protein expressions of c-Jun N-terminal kinase(JNK), p-JNK, p53, p-p53 and Bax in prefrontal cortex of rats in each group were detected by Western blot at the 4th and 8th week after modeling.SPSS 17.0 software was used for data analysis, one-way ANOVA was used for comparison between groups, and SNK-n q was used for pairwise comparison.n Results:The expressions of p-p53, p53, p-JNK, JNK and Bax in prefrontal cortex of normal group, depression group, stroke group and PSD group were significantly different at the end of 4th and 8th week after MCAO modeling (n F=3.426-90.355, all n P<0.05). Post-hoc analysis showed that, compared with the normal group, the expressions of p-JNK (0.378±0.042) and Bax (0.478±0.054) in the prefrontal cortex of PSD rats increased significantly at the end of the 4th week(bothn P<0.05), and the expressions of p-JNK(0.411±0.056), p-p53 (0.286±0.083) and Bax (0.471±0.008) in the prefrontal cortex of PSD group increased significantly at the end of the 8th week(alln P<0.05). After lateral ventricle injection of proBDNF, there were significant differences in the expression of p-p53, p53, p-JNK, JNK and Bax among proBDNF group, tPA group and NS group (n F=16.915-287.039, all n P<0.01). Post-hoc analysis showed that, compared with NS group, the expressions of p-JNK (0.35±0.01)and p-p53 (0.31±0.01)in prefrontal cortex of proBDNF group increased significantly(bothn P<0.05). After lateral ventricle injection of proBDNF, there were significant differences in body weight, sucrose preference rate, horizontal movement distance among proBDNF group, tPA group and NS group (n F=18.741-76.305, all n P<0.01), and compared with tPA group and NS group, behavioral indexes of proBDNF group (body weight (224.36±3.23) g, sucrose preference rate (69.83±1.72)%, horizontal movement distance (57.93±2.09) blocks, vertical movement distance (19.79±1.81)) decreased significantly(alln P<0.05).n Conclusion:The proBDNF promotes the activation of apoptosis signal pathway in the rats with PSD.