| Background:Ageing of the population is an important problem which is the present society pays close attention to.Postoperative cognitive dysfunction is a subtle disorder of thought processes that may influence isolated domains of cognition such as verbal memory,visual memory,language comprehension,visuospatial abstraction,attention,or concentration.POCD seriously affects quality of life of the aging.It can lead to delay of rehabilitation and increase medical cost.So looking for an available pathway to prevent and cure the POCD of the old is an important problem of the medicine world now.POCD is a result of many factors interacting,the potential reasons and risk factors including, cardiopulmonary bypass,general anesthetics,hypoxemia,hyperlipemia,hypotension and so on.The age is an independent factor in the processes of POCD.With the increasing of age,central nerve can degenerate and its function can descend.Because of the transmutation of physiological functions,for instance,the degeneration of cholinergic neuron in the brain,the reduction of acetylcholine and number of its receptors,all of which can raise the sensibilities of anesthetic drugs in the old. Penehyclidine hydrochloride is a new selective cholinolytic drug made in China,which can selectively affect M1 and M3 receptor,but hardly affect M2 receptor.Also it can easily permeate blood brain barrier,but whether it can inhibit cognitive function in the aged patients or not,there is no records in and abroad.Objective:Experiments were carried out on 18-month-old female and male Sprague-Dawley rats with no dyskinesia,and the animals received intraperitoneal penehyclidine hydrochloride,scopolamine, (1)observing effects of these two different cholinolytic drugs on cognitive function in aged rats(2)observing changes on AChE in the hippocampus and ChAT in the basal forebrain of aged ratsMethods:Twenty-four Sprague Dawley rats aged 18 months were randomly divided into 3 groups(group P,group S and group C)with 8 rats each.They were trained 1 times in the water maze test,so that the rats with dyskinesia could be derived out.Then 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 3 days.One day after the last drug administration, the animals underwent Morris water maze test 4 times a day for 3 consecutive days(the 1st day,the 2nd day and the 3rd day),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 using immunohistochemistry.The data are expressed as mean±SEM. Statistical analysis of the data was performed using ANOVA, Significance was accepted at P＜0.05.Results:(1)Morris water maze:The latency periods of 3 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 day of water maze test than that on the 1st day in group N 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).(2)ACHE:The AChE expression was higher significantly in group S than those in group C in the district of CA1 and DG of the old age (P＜0.05).(3)CHAT:The ChAT expression was lower significantly in group S than those in group C in the district of basal forebrain(VDB and HDB)of the old age(P＜0.05).Conclusion:With the dose of this experiment,Penehyclidine hydrochloride(0.64 mg·kg-1·d-1)may not have any significant effect on spacial cognitive function,whereas scopolamine(0.29 mg·kg-1·d1has an inhibitory effect on it in aged rats,which may be because of the elective effects of M2 receptor in scopolamine.And the absence of M2 receptor in Penehyclidine hydrochloride may be the reason of its no effect on spacial cognitive function of the old rats. |
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