| Aging is a complex biological process,which is mainly manifested the changes in the structure and function of the body system.The high level of oxidative stress caused by the excessive oxygen radical and the decrease of antioxidant capacity is one of the common mechanisms of aging.Studies have shown that the disorder of DAnergic system was found in the brain of aging rats,the activation of antioxidant system could improve the function of DAnergic system in the brain of the natural aging rats.Prior to this,we found that pentoxifylline can improve the levels of DA,DOPAC and HVA in CPu and HVA of D-galactose induced aging rats.In the present study,D-galactose induced aging rats model was adopted in the present studys,through oral administration of experimental animal with different doses of pentoxifylline.The qPCR was used to detect the TH mRNA and DAT mRNA in substantia nigra(SN);Western blot was used to detect the TH and DAT protein in SN and caudate putamen(CPu);detect the oxidative stress parameters(MDA,LPO,GSH,SOD)in SN and CPu by the spectrophotometry;to explore the possible mechanism of the amelioratory effect of pentoxifylline treatment on DAnergic neuron 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 effect of pentoxifylline treatment on the oxidative stress in SN and CPu and explore the possible mechanism of the amelioratory effect of pentoxifylline treatment on DAnergic neuron of D-galactose induced aging rat model,and hope to provide experimental basis for the treatment of neurodegenerative diseases such as aging.60 male Wistar rats were randomly divided into five groups: Control group(CON,n=12),D-galactose induced aging rats(D-galactose,n=12),D-galactose + pentoxifylline 10mg/kg(PTX10mg,n=12),D-galactose + pentoxifylline 30mg/kg(PTX30mg,n=12)and D-galactose + pentoxifylline 50mg/kg(PTX50mg,n=12).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.All animals were sacrificed on the day 58.The qPCR was used to detect the TH mRNA and DAT mRNA in SN;Western blot was used to detect the TH and DAT protein in SN and CPu;detect the oxidative stress parameters(MDA,LPO,GSH,SOD)in SN and CPu by the spectrophotometry.Results:1 qPCR: Compared with CON group,the level of TH mRNA and DAT mRNA in SN were significantly reduced in D-galactose group.Treatment of pentoxifylline could dose-dependently increased the levels of TH mRNA and DAT mRNA in SN of aging rats induced by D-galactose.2 Western blot: Compared with CON group,the expression of TH and DAT in SN and CPu were significantly reduced in D-galactose group.Treatment of pentoxifylline could dose-dependently increased the expression of TH and DAT in SN and CPu of aging rats induced by D-galactose.3 Spectrophotometry: Compared with CON group,the levels of oxidative damage parameter MDA and LPO in SN and CPu were significantly increased in D-galactose group.Treatment of pentoxifylline could dose-dependently decreased the levels of MDA and LPO in SN and CPu of aging rats induced by D-galactose.Compared with CON group,the levels of antioxidant index GSH and SOD in SN and CPu were significantly decreased in D-galactose group.Methods: Treatment of pentoxifylline could dose-dependently increased the levels of GSH and SOD in SN and CPu of aging rats induced by D-galactose.Conclusion:1 Declined function of DAnergic neuron was found in D-galactose induced aging rat model.2 Pentoxifylline ameliorate the defect of DAnergic activity in CPu and Acb of aging rat induced by D-galactose.3 Pentoxifylline decreased the oxidative damage in CPu and Acb of aging rat induced by D-galactose. |
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