参芎化瘀胶囊预处理对脑缺血再灌注大鼠海马CAl区细胞凋亡及原癌基因c-fos、c-jun表达的影响

Effect of Shenxiong-Huayu capsule preconditioning on cell apoptosis and the expression of C-los and C-jun in the hippocampal CA1 area of rats with cerebral ischemia reperfusion injury

目的观察参芎化瘀胶囊预处理对脑缺血再灌注大鼠海马CAl区细胞凋亡及c-fos、c-jun表达的影响。方法将SD大鼠采用完全随机的方法分为假手术组（24只）、脑缺血再灌注组（模型组24只）和参芎化瘀胶囊预处理组（预处理组24只）。假手术组、模型组给予生理盐水1ml灌胃，预处理组给予参芎化瘀胶囊生理盐水混悬液1ml（480mg）灌胃。均给药7d，1次／d。第7天给药2h后，用线栓法制作大脑中动脉阻断再灌注模型（MCAO）。采用TUNEL法检测细胞凋亡，免疫组织化学法检测c-fos、c-jun的表达。结果①模型组6、24、48、72h海马CAl区细胞凋亡数分别为（11．17±3．71、39．83±5．67、48．33±5．32、22．17±3．71）个／高倍视野，预处理组分别为（7．83±2．04、15．00±3．58、29．50±6．89和10．17±2．32）个／高倍视野。与模型组比较，预处理组不同时间点凋亡细胞减少（P〈0．05或P〈0．01）。②模型组6、24、48、72h海马CAl区c-fos表达分别为（14．50±3．45、33．67±1．63、42．33±3．32、32．00±2．90）个／高倍视野，预处理组分别为（10．17±2．93、21．50±2．43、30．83±3．76、25．17±5．27）个／高倍视野。模型组6、24、48、72h海马CAl区c-jun表达结果分别为（15．50±4．19、22．83±5．64、33．10±4．19、14．67±3．08）个／高倍视野，预处理组分别为（9．67±3．63、15．67±2．73、21．26±3．63和9．33±3．61个／高倍视野。与模型组比较，预处理组不同时间点c-fos、c-jun表达减少（P〈0．05或P〈0．01）。结论预处理组可通过抑制c-fos、c-jun表达，减少细胞凋亡，对大鼠脑缺血再灌注损伤具有保护作用。

[Abs Objective To observe the effect of Shenxiong-Huayu Capsule preconditioning on cell apoptosis and the expression of c-fos, c-jun in the hippocampal CA1 area of rats with acute cerebral ischemia reperfusion injury. Methods SD rats were divided into 3 groups by completely randomized method： sham operation group（n = 6）, ischemia reperfusion group （model group）, and Shenxiong-Huayu Capsule preconditioning group （preconditioning group）. The last two groups were divided randomly into 6 h, 24 h, 48 h and 72 h reperfusion subgroups （each n=6）. Intragastric administration for 7 days, once a day. Middle cerebral artery occlusion and reperfushion model was made by an intralurninal filament method. Cell apoptosis was detected by TUNEL method, the expression of c-fos, c-jun was observed by immunohistochemistry. Results ①The number of apoptosic cells at 6, 24, 48, 72 h in the hippocampal CA1 area of rats was respectively （11.17± 3.71, 39.83±5.67, 48.33 ±5.32 and 22.17±3.71） single/High power field in the model group, and was respectively （7.83±2.04, 15.00±3.58, 29.50±6.89 and 10.17 ±2.32） single/High power field in Shenxiong-Huayu Capsule preconditioning group. Compared with the model group, the number of apoptosic cells at each time point in thehippocampal CA1 area of rats was decreased in Shenxiong-Huayu Capsule preconditioning group （P〈 0.05 or P〈0.01 ） .②The number of c-los at 6、24、48、72 h in the hippocampal CA1 area of rats was respectively （14.50 ± 3.45,33.67 ± 1.63,42.33 ± 3.32 and 32.00 ± 2.90） single/High power field in the model group, and was respectively （10.17 ± 2.93, 21.50 ± 2.43, 30.83 ± 3.76 and 25.17 ± 5.27） single/High power field in Shenxiong-Huayu Capsule preconditioning group.The number of c-jun at 6, 24, 48, 72 h in the hippocampal CA1 area of rats was respectively （15.50±4.19, 22.83±5.64, 33.10±4.19 and 14.67±3.08） single/High power field in the model group, and was respectively （9.67 ± 3.63, 15.67 ± 2.73, 21.26 ± 3.63 and 9.33 ± 3.61） single/High power field in Shenxiong-Huayu Capsule preconditioning group.Compared with the model group, the expression of c-los, c-jun at each time point in the hippocampal CAI area of rats was decreased in Shenxiong-Huayu Capsule preconditioning group （P〈0.05 or P〈0.01 ） . Conclusion Shenxiong-Huayu capsule can inhibit apoptosis by restraining the expression of c-fos, c-jun and relive cerebral ischemia reperfusion injury in rats.