| Objective:Resveratrol is in many plants of a natural anti-toxin,a large number of studies have found the antioxidant resveratrol can activate SIRT1 genes and prevent or delay the occurrence and development of many diseases related to old age. Caloric restriction also can stimulate the expression of SIRT1 like aging.Both the effect and mechanism of aging are described so much,but both the role of a comparative study rarely reported herein delaying action mechanisms of aging between resveratrol and caloric restriction, to explore whether there is the same or a similar mechanism of action between them, Comparison of resveratrol and caloric restriction anti-aging effect, to explore whether resveratrol can as the best fit agonists of calorie restriction,then can help the clinical treatment of diseases related to old age, and help health care and anti-aging scientific,it can as one of effective reference and methodological guidance.Methods: SPF level 50 male Wistar rats, weighing 200 ± 10 g,randomly divided into five groups: normal group, model group,calorie restriction group, resveratrol low dose group, high dose of resveratrol. Model group, low dose of resveratrol, resveratrol high-dose group,calorie restriction group,to establish aging model by intraperitoneal injection D-galactose 250mg/kg/d, at the same time,low of resveratrol dose group, high dose group were respectivily given resveratrol 100mg/kg/d,200mg/kg/d,the normal group, model group, low-dose resveratrol group,high dose group food intake 100 g /kg/d,calorie restriction group is 60%×100g/kg/d,the experimental lasts 6 weeks.During the experiment on the general state of mental rat,fur, activities were observed;every four days each group weighed weight, comparing the rate of change in body weight,Morris water maze test, the rats learn to change test behavior;detecting liver and brain tissue antioxidant related indicators:SOD,MDA,T-AOC;enzyme-linked immunosorbent otation of telomerase activity was measured rats;immunohistochemical methods detecte SIRT1 transcription level important regulatory factor p53 and FOXO3a; the use of the expression by RT-PCR to detect rat SIRT1 m RNA of longevity genes;Western blot method detect protein expression levels of p53,FOXO3 a,Hu R(ELAVL1), RPS19BP1, DBC1.Results:(1)General state observation:it is observed that normal group is in good diet and good spirits;model group is lack of energy,they get together,dark coat color rough,gradual depilation and unresponsive with less activity;mental state rats resveratrol low dose and high dose group of good, normal appetite, responsive,activities more, shiny coat supple skin elasticity; calorie restriction group spirit more excitement, diet, reaction, active are no significant difference with resveratrol groups.(2)Changes in body weight ratio:For each group,the rate of change in mass Rat ANOVA at each time point display:caloric restriction group than in the other the body weight increased slowly,there was a significant difference(P<0.05).(3)Behavioral experiments:Resveratrol low and high dose groups,calorie restriction rats escape latency,swimming speed, increase the number of crossing the target quadrant, resveratrol high dose group was significantly better than calorie restriction group(P<0.05),resveratrol low dose group and the caloric restriction group had no significant difference(P>0.05).(4)Liver and brain tissue antioxidant indexes:Compared with normal group,D-galactose induced aging model rat in liver tissue, the activity of SOD, T-AOC viability was significantly lower(P<0.05),MDA content increased significantly(P<0.05); high dose resveratrol significantly increased calorie restriction group compared to the activity of SOD, T-AOC vigor was also significantly increased, MDA content significantly reduced(P<0.05), resveratrol high dose group better than the relative effect of calorie restriction group.Compared with normal group, D-galactose-induced rat brain aging model group, SOD activity decreased significantly, T-AOC viability was significantly lower(P<0.01), a significant increase in MDA content(P <0.01);a significant increase in the high dose group than resveratrol calorie restriction group SOD activity, T-AOC vigor was also significantly increased,MDA content significantly reduced(P<0.05),there was no significant differences between low doses of resveratrol and caloric restriction group,resveratrol high dose group opposite effect than caloric restriction group.(5)Determination of telomerase activity in brain tissue: Compared with model group, the normal group telomerase activity was significantly higher(P<0.01); calorie restriction group was significantly higher telomerase activity than resveratrol high dose group(P<0.05), caloric restriction group for improving brain tissue telomerase activity of resveratrol than the high dose group.(6)The relative expression of SIRT1 m RNA, p53 m RNA and FOXO3 am RNA by RT-PCR:in liver tissue, the calorie restriction group SIRT1 m RNA relative expression levels were significantly higher than resveratrol low dose group, there was significant difference(P<0.05), caloric restriction group SIRT1 m RNA relative expression compared with high-dose resveratrol group was no significant difference(P>0.05), caloric restriction group p53 m RNA resveratrol relative expression amount was less than the low-dose group, there was a significant difference(P<0.05), caloric restriction group FOXO3 am RNA relative expression compared with resveratrol significantly increase the low-dose group, there was a significant difference(P<0.05); D-galactose on rat brain, resveratrol low and high dose group SIRT1 m RNA relative expression levels higher than calorie restriction group, there was a significant difference(P<0.05), high dose group p53 m RNA resveratrol relative expression was significantly reduced compared with the amount of calorie restriction group, a significant differences(P<0.05),resveratrol low and high dose group FOXO3 am RNA relative expression of calorie restriction group was no significant difference(P>0.05).(7)Western Blot detection of brain tissue after SIRT1 transcription levels of p53,FOXO3 a, Hu R(ELAVL1), RPS19BP1 and DBC1 proteins: p53 protein levels:resveratrol low dose group p53 protein expression was increased than the calories restriction,high dose resveratrol group p53 protein expression and caloric restriction group had no significant difference; FOXO3 a protein levels: calorie restriction group higher than the low dose group FOXO3 a resveratrol increased protein expression,calorie restriction group and high dose resveratrol group FOXO3 a protein expression had no significant difference;RPS19BP1 protein level:low dose resveratrol group RPS19BP1 expression reduced compared with calorie restriction group, the high dose group RPS19BP1 resveratrol and caloric restriction group expression were no significant difference; Hu R protein level: high dose resveratrol group Hu R protein expression increased than calorie restriction group,there was no significant difference in reducing resveratrol low dose group Hu R protein expression and the calorie restriction group; DBC1 protein level:high dose resveratrol group DBC1 protein expression significantly reduced than caloric restriction. There was no significant difference between low dose resveratrol group DBC1 protein expression and caloric restriction group.Conclusions: Resveratrol had a better improvement on learning and memory capacity,enhance the role of the body's antioxidant capacity than calorie restriction, it can also increase telomerase activity in aging rats to a certain extent. By comparison the molecular level mechanism, resveratrol and caloric restriction could promote SIRT1,FOXO3 a gene expression, reducing the expression of p53 gene,can promote post-transcriptional level factor and the translation factor FOXO3 a,Hu R, RPS19BP1 expression protein level,reduce the expression of p53 protein, the expression of DBC1 protein,indicating that resveratrol for SIRT1 and its associated transcription factor regulating capacity stronger than calorie restriction.Overall, resveratrol relative to calorie restriction has a better anti-aging effect,you can avoid the need for willpower to control caloric restriction based on a strict diet limited to a certain extent. |
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