三七总皂昔对全脑缺血后抑郁大鼠抑郁行为及海马神经再生的影响

Effects of total saponins of panax notoginseng on depressive behavior and hippocampal nerve regeneration in rats with following global cerebral ischemia depression

目的探讨三七总皂苷(total saponins of panax notoginseng,TSPN)对全脑缺血后大鼠抑郁样行为的作用及其机制。方法采用四血管阻断法制作全脑缺血模型,7 d后采用社会隔离+慢性不可预见性温和应激(CUMS)法制备大鼠脑缺血抑郁模型。70只大鼠被随机分为假手术组(Sham组,n=10)、全脑缺血模型组(Model组,n=20)、全脑缺血后抑郁组(PSD组,n=20)、PSD+三七总皂苷组(TSPN组,n=20)。Sham组只分离两侧颈总动脉,不夹闭,不给予干预;Model组和PSD组在脑缺血后30 min再灌注,腹腔注射等体积生理盐水,1次/d;TSPN组给予抑郁大鼠腹腔注射TSPN,1次/d(剂量为75 mg/kg,浓度为10 g/L)。再灌注30 d后对各组大鼠抑郁样行为进行检测,免疫组织化学观察海马齿状回颗粒细胞下层(SGZ区)BrdU(外源性细胞增殖标记物)和doublecortin(DCX,微管相关蛋白)的表达。结果PSD组糖水偏好百分比显著低于Model组[(46.2±9.2)%,(61.2±7.6)%;t=3.18,P<0.05],与PSD组相比,TSPN组大鼠的糖水消耗显著增加[(62.4±3.4)%,(46.2±9.2)%;t=3.43,P<0.05]。强迫游泳实验中PSD组不动时间与Model组相比差异显著增加[(119.4±9.7)s,(88.0±15.6)s;t=4.30,P<0.01];与PSD组比较,TSPN组大鼠的不动时间显著缩短[(97.4±6.7)s,(119.4±9.7)s;t=3.01,P<0.05]。与Model组相比[BrdU+:(12.6±2.2)个/mm2,DCX+:(38.6±4.2)个/mm2],PSD组大鼠海马SGZ区BrdU+和DCX+细胞显著减少[BrdU+:(8.8±1.5)个/mm2,DCX+:(27.2±2.8)个/mm2;t=3.25,P<0.05;t=4.29,P<0.01];与PSD组相比,TSPN组大鼠海马SGZ区BrdU+和DCX+细胞显著增加[BrdU+:(14.8±2.8)个/mm2,DCX+:(37.0±3.3)个/mm2;t=4.68,P<0.01;t=3.69,P<0.05]。结论三七总皂苷可改善全脑缺血后大鼠抑郁样行为,其机制可能是与促进海马神经再生有关。

Objective To explore the effect of the total saponins of panax notoginseng (TSPN) on depression-like behavior following global cerebral ischemia depression in rats and its mechanism. Methods Using four-vessel occlusion method to build the global cerebral ischemia model, then the cerebral ischemia rats were given solitary breeding with chronic unpredictable mild stress(CUMS) to prepare depression model.Seventy rats were divided into sham group (n=10), model group (n=20), PSD group (n=20) and TSPN group (n=20). The rats in the TSPN group were administered TSPN intraperitoneally 30 min post-brain ischemia.The dose of TSPN (75mg/kg) was suspended in 0.9% saline 10g/L, once per day for 30 days after reperfusion.While rats in the vehicle group and PSD group was treated with equal volume of 0.9% saline, one injection per day until the rats were sacrificed at 30 days after brain ischemia.The BrdU, doublecortin (DCX) expression in the hippocampus was assessed by immunohistochemistry. Results In comparison with the model group, the sucrose preference percentage in the PSD group was significantly lower ((46.2±9.2)%,(61.2±7.6)%;t=3.18, P<0.05), then the PSD rats were administered TSPN intraperitoneally, the sucrose preference percentage increased significantly ((62.4±3.4)%,(46.2±9.2)%;t=3.43, P<0.05). During the forced swimming test, the immobility time of PSD group was significantly increased compared with the model group ((119.4±9.7)s,(88.0±15.6)s;t=4.30, P<0.01), while after PSD rats administering TSPN intraperitoneally, the immobility time was shorten remarkably ((97.4±6.7)s,(119.4±9.7)s;t=3.01, P<0.05). Compared with the Model group(BrdU+:(12.6±2.2)/mm2, DCX+:(38.6±4.2)/mm2), the number of BrdU+ and DCX+ cells in the SGZ of hippocampus in PSD group decreased (BrdU+:(8.8±1.5)/mm2, DCX+:(27.2±2.8)/mm2;t=3.25, 4.29, both P<0.01). And compared with PSD group, the number of BrdU+ and DCX+ cells in the SGZ of hippocampus in TSPN group increased significantly (BrdU+:(14.8±2.8)/mm2, DCX+:(37.0±3.3)/mm2;t=4.68, 3.69, both P<0.05). Conclusion TSPN can improve the depression-like behavior of rats following global cerebral ischemia, which may be related with promoting hippocampal nerve regeneration.