Research Of The Mechanism Of Cognitive Dysfunction By Penequinine Hydrochloride In Aged Rats

Objective: At different time, after intraperitoneal injection ofdifferent dose of penequinine hydrochloride(PHC) in aged rats, toobserve their cognitive function and relevant acetylcholine(Ach) level,acetylcholine esterase(AChE) activity, positive cells level of glialfibrillary acidic protein (GFAP),which is the symbol of astrocyte, andS-100β protein content in hippocampus. To explore the possiblemechanism of postoperation cognitive dysfunction caused by PHC.Toprovide basic theory and clinical evidence of preoperative administrationof optimum dose of PHC. Methods: One-hundred sixty aged rats wererandomly divided into control group (k), low penequinine hydrochloridegroup(LP), medium group (MP) and high group(HP), NS,0.32mg/kg,0.64mg/kg and1.28mg/kg PHC (the standard of liquid volume is0.1ml/10g) injected respectively. At6h,12h,24h,48h and72h afteradministration of PHC,8rats at each time point in each group, theirlearning ability was detected by the Morris water maze. Level of Ach andactivity change of TChE in hippocampus were detected by colorimetry.Protein level was detected by Ma Siliang blue. S-100β protein content inhippocampal was detected by ELISA. Immunity positive cells quantity ofGFAP in hippocampal were detected by immunohistochemistry. Results: 1. Morris water maze results: The escape latency was gradually shortenedduring5days before PHC injection, the escape latency and anchorseeking frequency were no significant difference in all groups (P>0.05).At6and12h after administration, compared with group K, the escapelatency lengthened significantly and anchor seeking frequency decreasedsignificantly in PHC injection groups (P<0.05), and compared with groupLP，the escape latency lengthened significantly and anchor seekingfrequency decreased significantly in group MP and HP (P<0.05). At24,48and72h after administration, there were no significant difference ofthe escape latency and anchor seeking frequency between group K andLP, and between group MP and HP (P>0.05). Compared with group Kand LP, the escape latency lengthened significantly and anchor seekingfrequency decreased significantly in group MP and HP (P<0.05).Compared with6and12h, escaped latency shortened significantly andanchor seeking frequency increased significantly at24,48and72h ingroup LP(P<0.05), but both were no significant difference within groupMP and HP(P>0.05).2. Activity of TChE and level of Ach: At6and12h,compared with group K, TChE activity increased and Ach level decreasedin injection PHC group (P<0.05). At24,48and72h, there was nosignificant difference between group K and LP(P>0.05), and comparedwith group K and LP, TChE activity increased and Ach level decreased ingroup MP and HP(P<0.05). There was significantly difference between group MP and HP at24,48and72h (P<0.05). Compared with6and12h,TChE activity decreased significantly and Ach level increasedsignificantly at24,48and72h in group LP(P<0.05). Compared with6and12h, TChE activity increased significantly and Ach level decreasedsignificantly at24,48and72h in group MP and HP (P<0.05).3. Positivecells of GFAP: At6and12hs after administration, there was nosignificant difference in all groups (P>0.05). At24,48and72h, there wasno significant difference between group K and LP(P>0.05). Comparedwith group K and LP, GFAP positive cells increased in group MP and HPat24,48and72h (P<0.05). Compared with group MP, GFAP positivecells significantly increased in group HP at24,48and72h (P<0.05).There was no significant difference of GFAP positive cells between groupK and LP(P>0.05)at all time points. Compared with6and12h, GFAPpositive cells were significantly higher at48and72h in group MP and HP(P<0.05). Compared with24h, GFAP positive cells were significantlyhigher at48and72h in group MP(P<0.05).4. S-100β proteinconcentration: At6and12h, there was no significant difference in allgroups (P>0.05). At24,48and72h, there was no significant differencebetween group K and LP (P>0.05). Compared with group K and LP,S-100β protein concentration increased significantly in group MP and HPat the three time points(P<0.05). The protein concentration in group HPincreased significantly than group MP at the three time points (P<0.05). There was no significant difference of S-100β protein concentrationbetween group K and LP(P>0.05)at all time points. Compared with6and12h, protein concentration was significantly higher at48and72h in groupMP and HP(P<0.05). Compared with24h, protein concentration wassignificantly higher at48and72h in group MP(P<0.05). Conclusions:1.Penequinine hydrochloride could result in memory dysfunction in agedrats,with dose dependent manner.2. High dose PHC at the level of0.64mg/kg,1.28mg/kg, result in AchE activity increased,Ach leveldecreased,GFAP positive cells increased and S-100β proteinconcentration which will be the possible mechanisim of cognitivedysfunction caused by penequinine hydrochloride in aged rats.