人参皂甙Rd对氯胺酮诱导幼年大鼠海马神经元凋亡的影响

Effect of ginsenoside-Rd injection on ketamine-induced neuroapoptosis in infant rat hippocampus

目的探讨人参皂甙Rd（GSRd）对于氯胺酮诱导幼年Sprague-Dawley（SD）大鼠海马神经元凋亡的影响。方法 35只幼年（出生后第7天）SD雄性大鼠随机分入对照组（10只）、氯胺酮组（10只）、氯胺酮＋GSRd预处理高剂量组（5只）、氯胺酮＋GSRd预处理低剂量组（5只）、GSRd组（5只）。氯胺酮组、氯胺酮＋GSRd预处理高剂量组、氯胺酮＋GSRd预处理低剂量组大鼠均予单次腹腔注射氯胺酮80mg/kg行麻醉处理,对照组、GSRd组则给予腹腔注射相同体积的0.9%氯化钠溶液。在氯胺酮注射前48、24和0.2h时,氯胺酮＋GSRd预处理高剂量组、氯胺酮＋GSRd预处理低剂量组和GSRd组大鼠均连续3次腹腔注射GSRd,3组的剂量分别为100、5~40和100mg/kg。麻醉10min后,检测大鼠动脉血pH值、动脉血氧分压（paO2）、动脉二氧化碳分压（paCO2）。大鼠苏醒后即刻,采用Western印迹法检测大鼠海马神经元活化型半胱氨酸天冬氨酸蛋白酶3（Caspase 3）和抗凋亡因子（Bax）的相对分子质量,记录不同剂量的GSRd对氯胺酮诱导后大鼠海马神经元凋亡的影响。结果麻醉10min后,氯胺酮组与对照组间动脉血pH值、paO2、paCO2的差异均无统计学意义（P值均〉0.05）。氯胺酮组的活化型Caspase 3、Bax相对分子质量均显著高于对照组和GSRd组（P值均〈0.05）,氯胺酮＋GSRd预处理高剂量组显著高于氯胺酮组和氯胺酮＋GSRd预处理低剂量组（P值均〈0.05）,氯胺酮组与氯胺酮＋GSRd预处理低剂量组间、对照组与GSRd组间的差异均无统计学意义（P值均〉0.05）。结论低剂量GSRd对氯胺酮诱导的幼年大鼠的海马神经元凋亡无影响,而高剂量GSRd增加了海马神经元的凋亡。GSRd对于氯胺酮诱导的幼年大鼠的海马神经元凋亡无保护作用。

Objective To explore the effect of ginsenoside-Rd （GSRd） injection on ketamine-induced neuroapoptosis in infant rat hippocampus. Methods Thirty-five Sprague-Dawley rat aged 7 days old were randomly divided into five groups, control group （n = 10）, ketamine group （n = 10）, ketamine plus pretreatment with high dose of GSRd group （K＋ HG group, n=5）, ketamine plus pretreatment with low dose of GSRd group （K＋LG group, n = 5）, and GSRd group （n = 5）. Ketamine （80 mg/kg） were injected intraperitoneally in ketamine group, K＋ HG group and K＋ LG group; the same volume of normal saline was injected in control group and GSRd group. Additionally, GSRd （100, 5- 40, 100 mg/kg） was injected intraperitoneally in K ＋ HG group, K＋LG group and GSRd group, respectively, at 48 h, 24 h and 0.2 h before ketamine exposure. Arterial pH, partial pressure of oxygen （ PaO2 ）, and partial pressure of carbon dioxide （ paCO2 ） were monitored 10 minutes after anesthesia. The relative molecular weight of activated Caspase 3 and Bax in the hippocampus was measured by Western blot when the rats revived. Results There were no significant differences in the levels of arterial pH, paO2 or paCO2 between ketamine group and control group （all P〉 0. 05）. The relative molecular weights of activated Caspase 3 and Bax in ketamine group were significantly higher than those in control group and GSRd group （both P〈0. 05）. The expression of activated Caspase 3 and Bax in K＋HG group were significantly higher than those in ketamine group and K ＋ LG group （both P〈O. 05）. There were no significant differences in the relative molecular weight of activated Caspase 3 and Bax between ketamine group and K ＋ LG group （both P〉 0.05） or between control group and GSRd group （both P〉O. 05）. Conclusion Low dose of GSRd does not increase ketamine-induced apoptosis in hippocampus, while high dose of GSRd promotes neurodegeneration. GSRd cannot protect against ketamine-induced apoptosis in infant rat hippocampus. （Shanghai Meal J, 2014, 37： 314-317）