| Aging is a natural process of human body with the passage of time,the main manifestation is the degeneration of the body structure and the organ function,often accompanied by reduced movement,memory capacity,serious impact on people’s quality of life,how to prevent or alleviate the aging related changes is one of the hot issues in current research.At present,the effects of anti aging drugs are not ideal,some studies have found that pentoxifylline can improve the learning and memory impairment of natural aging rat model and scopolamine induced aging mice model.No study has been focus on whether pentoxifylline can improve the open field behavior of D-galactose induced aging rat model.Therefore,D-galactose induced aging rats model was adopted in the present studys,through oral administration of experimental animal with different doses of pentoxifylline,observe the effects of pentoxifylline treatment on D-galactose induced aging rat model of weight gain;the effects of pentoxifylline on the behavior of D-galactose induced aging rats were observed by open field test;the changes of DA,DOPAC and HVA in the brain of rats were determined by LC-MS/MS,the effect of pentoxifylline on the function of DA neurons in the rat model of D-galactose induced aging,to explore the possible mechanism of pentoxifylline treatment on the open field behavior of D-galactose induced aging rat model,and hope to provide experimental basis for the treatment of neurodegenerative diseases such as aging.Objective: To observe the effects of pentoxifylline on the open field test and DA or its metabolites in the caudate putamen and nucleus accumbens of in the rat model of D-galactose induced aging.Exploring the possible mechanism of pentoxifylline treatment on the open field behavior of D-galactose induced aging rat model,and hope to provide experimental basis for the treatment ofneurodegenerative diseases such as aging.Methods:40 male Wistar rats were randomly divided into five groups:Control group(CON,n=8),D-galactose induced aging rats(D-galactose,n=8),D-galactose+pentoxifylline 10mg/kg(PTX10mg,n=8),D-galactose +pentoxifylline 30mg/kg(PTX30mg,n=8)and D-galactose + pentoxifylline50mg/kg(PTX50mg,n=8).Starting from the age of 3 months(day 0),Wistar rats received 57 daily intraperitoneal(i.p.)injections of saline or D-galactose(150 mg/kg/day).Respective groups of D-galactose-treated or PTX rats received pentoxifylline treatment(10,30 or 50 mg/kg daily,p.o.)starting from the age of 3 months during 57 days.Rats were weighed weekly during the experiment to correct drug dosages.To assess the effects of experimental factors on body weight gain,the values of body weight measured before the sacrifice of animals were analyzed.In the last week of treatment,all animals were subjected to the open field test on the day 56–57.The rats were sacrificed on the day 58.The contents of DA,DOPAC and HVA in the caudate putamen and nucleus accumbens were detected by LC-MS/MS.Results:1 Open filed test1.1 Immobile-sniffingCompared with CON group,the number of immobile-sniffing was significantly reduced in D-galactose group(P<0.01);compared with Dgalactose group,the number of immobile-sniffing was significant increased in PTX50 group(P < 0.01).1.2 Exploratory behaviorsCompared with CON group,the number of walking was significantly reduced in D-galactose group(P < 0.01);compared with D-galactose group,the number of walking was significant increased in PTX30 group and PTX50group(P < 0.01);compared with PTX10 group,the number of walking was significant increased in PTX50 group(P < 0.01).Compared with CON group,the number of climbing was significantlyreduced in D-galactose group(P < 0.01);compared with D-galactose group,the number of climbing was significant increased in PTX10 group(P < 0.01);compared with PTX10 group,the number of climbing was significant increased in PTX50 group(P < 0.01),but still lower than normal level.Compared with CON group,the number of rearing was significantly reduced in D-galactose group(P < 0.01);compared with D-galactose group,the number of rearing was significant increased in PTX10 group(P < 0.05);compared with PTX10 group or PTX30 group,the number of rearing was significant increased in PTX50 group(P < 0.05).Compared with CON group,the number of sniffing was significantly reduced in D-galactose group(P < 0.01);compared with D-galactose group,the number of sniffing was significant increased in PTX30 group and PTX50group(P < 0.01);compared with PTX10 group,the number of sniffing was significant increased in PTX50 group(P < 0.01).1.3 Motor behaviorsCompared with CON group,the vertical exercise value was significantly reduced in D-galactose group(P < 0.01);compared with D-galactose group,the vertical exercise value was significant increased in PTX10 group(P <0.01);compared with PTX10 group or PTX30 group,the vertical exercise value was significant increased in PTX50 group(P < 0.05).Compared with CON group,the horizontal exercise value was significantly reduced in D-galactose group(P<0.01);compared with D-galactose group or PTX10 group,the horizontal exercise value was significant increased in PTX30 group(P<0.05);compared with PTX30 group,the horizontal exercise value was significant increased in PTX50 group(P <0.01).Compared with CON group,the total length was significantly reduced in D-galactose group(P < 0.01);compared with D-galactose group or PTX10 group,the total length was significant increased in PTX30 group(P<0.05);compared with PTX30 group,the total length was significant increased in PTX50 group(P < 0.01).1.4 Grooming behaviorsCompared with CON group,the number of grooming was significantly reduced in D-galactose group(P < 0.01);compared with D-galactose group or PTX10 group,the number of grooming was significant increased in PTX30 group and PTX50(P < 0.01);compared with PTX30 group,the total length was significant increased in PTX50 group(P > 0.05).2 LC-MS/MS2.1 The effect of pentoxifylline on DA and its metabolite in CPuCompared with CON group,the level of DA was significantly reduced in D-galactose group(P < 0.01);compared with D-galactose group,the level of DA was significant increased in PTX10 group(P < 0.05);compared with PTX10 group,the level of DA was significant increased in PTX30 group(P <0.05);compared with PTX30 group,the level of DA was significant increased in PTX50 group(P < 0.01).Compared with CON group,the level of DOPAC was significantly reduced in D-galactose group(P < 0.01);compared with D-galactose group,the level of DOPAC was significant increased in PTX30 group(P < 0.01);compared with PTX30 group,the level of DOPAC was significant increased in PTX50 group(P < 0.05).Compared with CON group,the level of HVA was significantly reduced in D-galactose group(P<0.01);compared with D-galactose group or PTX10 mg group,the level of HVA was significant increased in PTX50 group(P < 0.01).2.2 The effect of pentoxifylline on DA and its metabolite in AcbCompared with CON group,the level of DA was significantly reduced in D-galactose group(P < 0.01);compared with D-galactose group or PTX10 mg group,the level of DA was significant increased in PTX30 group(P < 0.01);compared with PTX30 group,the level of DA was significant increased in PTX50 group(P < 0.01).Compared with CON group,the level of DOPAC was significantly reduced in D-galactose group(P < 0.01);compared with D-galactose group,the level of DOPAC was significant increased in PTX10 group(P < 0.05);compared with PTX10 group,the level of DOPAC was significant increased in PTX30 group(P < 0.05);compared with PTX30 group,the level of DOPAC was significant increased in PTX50 group(P < 0.01),but still lower than the level of control.Compared with CON group,the level of HVA was significantly reduced in D-galactose group(P < 0.01);compared with D-galactose group,PTX10 mg group or PTX50 mg group,the level of HVA was significant increased in PTX50 group(P < 0.05).The results indicated that pentoxifylline dose-dependently increased the levels of DA,DOPAC and HVA in CPu and Acb of aging rats induced by D-galactose.Conclusions:1 Deficit of open field behavior was found in D-galactose induced aging rat model.2 Pentoxifylline partly prevent the deficit of open field behavior in D-galactose induced aging rat model.3 Pentoxifylline partly prevent the effect of D-galactose on DA and its metabolites in CPu and Acb of rat. |
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