盐酸戊乙奎醚对老龄大鼠认知功能的影响

Effects of penehyclidine hydrochloride and scopolamine on cognitive function in aged rats

目的比较盐酸戊乙奎醚与东莨菪碱对老龄大鼠认知功能及大鼠海马乙酰胆碱酯酶(AChE)阳性纤维和基底前脑胆碱乙酰转移酶(ChAT)阳性细胞数量的影响。方法24只老龄SD大鼠,随机均分为盐酸戊乙奎醚组(P组)、东莨菪碱组(S组)及对照组(C组)。P、S组连续3d腹腔给药,剂量分别为0·64、0·29mg·kg-1·d-1,C组给予同等容积的生理盐水2ml。于停药后1d行水迷宫测试,记录潜伏期及游泳距离,连续测试3d。末次水迷宫测试后1h处死大鼠,用组织化学方法测定大鼠海马AChE以及免疫组化方法测定大鼠基底前脑ChAT的表达。结果三组3d潜伏期较1d缩短(P<0·05);S、C组3d游泳距离较1d缩短(P<0·05);S组水迷宫2d及3d潜伏期及游泳距离较C组显著延长(P<0·05)。S组大鼠海马AChE阳性纤维数量较C组显著增加(P<0·05),S组基底前脑ChAT阳性细胞数量较C组显著减少(P<0·05)。结论盐酸戊乙奎醚对老龄大鼠的认知功能无显著影响,东莨菪碱则对认知功能产生一定程度的抑制作用。

Objective To compare the effects of penehyclidine hydrochloride and scopolamine on spatial cognitive function and acetylcholinesterase （ACHE） in the hippocampus, choline acetyltransterase （CHAT） in the basal forebrain of aged rats. Methods Twenty-four Sprague Dawley rats aged 18 months were randomly divided into three groups with eight rats each. The animals received intraperitoneal （IP） penehyclidine hydrochloride 0.64 mg/kg （group P）, scopolamine 0. 29 mg/kg （group S） or normal saline 2 ml as the control（group C） per day for three days. One day after the last drug administration,the animals underwent Morris water maze test four times a day for three consecutive days, and the latency period and swimming distance were recorded. The animals were killed at 1 h after last test and the brains were immediately removed for determination of the expression of AChE in the hippocampus using histochemical stain,and the expression of ChAT in the basal forebrain was detected using immunohistochemistry. Results The latency periods of three groups were significantly shorter on the 3rd day of water maze test than those on the 1st day. The swimming distance was shorter on the 3rd clay of water maze test than that on the 1st clay in group C and S. The latency period and swimming distance on the 2nd and 3rd day of water maze test were longer in group S than those in group C （P〈0.05）. The AChE expression was higher, but ChAT expression was lower significantly in group S than those in group C （P〈 0.05 ）. Conclusion Penehyclidine hydrochloride （0.64 mg ·kg^-1·d^-1） may not have any significant effect on spatial cognitive function,whereas scopolamine （0.29 mg ·kg^-1·d^-1 ） has an inhibitory effect on it in aged rats.