| PurposeMilk-derived β-casomorphin-7 is the bioactive peptide derived from casein proteolysis,and has a variety of biological effects.The purpose of this study was to investigate whetherβ-CM-7 has a regulatory effect on dyslipidemia caused by aging and its possible mechanism.This study will provide scientific basis for the biological function of P-CM-7.It also provides new basic information for utilization of β-CM-7 to improve the health of the elderly.MethodsTwelve two-month-old and forty-eight eleven-month-old male Kunming mice were selected.After one week feeding under natural conditions,40 old mice were selected and randomly divided into the aged nonintervention group,the low-dose group,the medium-dose group and the high-dose group,according to the body weight,with ten mice in each group.Ten young mice were randomly selected as the young control group.Mice in the aged nonintervention group and the young control group were administered 0.5mL of normal saline,and mice in each dose group were administered equal volume of P-CM-7 solution with different concentration(0.2×10-6 mol/L、1×10-6 mol/L、5×10-6 mol/L)once a day for 4 weeks.All mice were weighed once a week.At the end of the operation,the eyeballs were removed to take blood,the mice were sacrificed by cervical dislocation,and the liver and pancreas were collected for testing.Changes of blood lipid levels,pancreatic hormone secretion,liver histopathological status,liver lipid content,lipid metabolism-related enzyme activity,relative expression of lipid metabolism genes,anti-oxidative stress and inflammatory factor levels were observed.Results(1)Effect of β-CM-7 on serum lipids of aged mice:P-CM-7 has no significant effect on the overall growth function of mice.Compared with the young mice,the serum TG level decreased(P<0.01),HDL-c level increased(P<0.05)significantly,and the INS level decreased,GLN level increased of the pancreas tissue(P>0.05)in the aged nonintervention group.Compared with the aged nonintervention group,the low-dose group mice had lower levels of GLU(P<0.05),HDL-c(P<0.05),and GLN(P<0.01),and higher levels of TG and INS(P<0.05).In the middle-dose group,HDL-c decreased(P<0.01)and INS increased(P<0.01).HDL-c levels were also significantly reduced in the high-dose group CP<0.01)(2)Effect of β-CM-7 on liver lipid metabolism in aged mice:H&E staining showed hepatic cord disorder,fuzzy nuclei,increased hepatocyte volume,particle degeneration,etc caused by aging.Different concentrations of(3-CM-7 can improve liver tissue damage to varying degrees.Compared with the young mice,the levels of ACC(P<0.05)and HSL(P<0.01)decreased,the LPL activity increased(P<0.05),the SREBP-1(P<0.05)and SCD1(P=0.05)gene was down-regulated in the aged nonintervention group.The CPT1 gene was also down-regulated(P>0.05)Compared with the aged nonintervention group,the ACC levels(P>0.05),HL activity(P<0.01)in mice were all increased,and LPL activity were decreased(P>0.05)after intervention with different concentrations of β-CM-7.Low-dose β-CM-7 decreased FAS and HSL levels,up-regulated CPT1 gene,and down-regulated ATGL gene significantly(P<0.05)of mice.The levels of FAS(P<0.05)and HSL(P=0.09)of liver tissues in medium-dose group mice decreased.The levels of liver TG(P<0.05),relative expression of SREBP-1c(P<0.01)and SCDI(P<0.05)increased in high-dose group.In addition,it was observed that both HSL level and SCD1 gene expression had a certain degree of dose-dependent effect with β-CM-7,while CPT1 gene expression was negatively correlated with it(3)Effect of β-CM-7 on liver oxidative stress and cytokines in aged mice:Compared with the young mice,the levels of SOD,MAO and MDA in the aged nonintervention group increased,and the levels of GSH-Px and IL-2 decreased,but all the differences were not significant(P>0.05)Compared with the aged nonintervention group,the SOD and GSH-Px activities of the mice in the low-dose group and the high-dose group were significantly increased(P<0.05),but the MAO and MDA levels were also increased.The lower SOD and higher GSH-Px activities of the medium-dose mice were not significant(P>0.05),while the MAO and MDA levels also decreased(P>0.05).At the same time,the liver IL-2 levels were extremely sensitive to low-concentration β-CM-7 stimulation(P<0.01),and there was no significant change in SIgA levels of mice in each dose group(P>0.05)ConclusionThe aging of the body may affect the shape and function of liver,cause oxidative stress,lipid metabolism disorders,and abnormal lipid metabolism in aged mice.There is a certain relationship between inflammatory factors and lipid metabolism disorder,but immune proteins are not reflected.β-CM-7 can alleviate oxidative stress,improve liver histopathological injury,and have a certain regulating effect on blood lipid metabolism disorders in aged mice.Its mechanism of action may be to regulate the secretion of hormones in the pancreatic tissue,increase the activity of fat synthesis-related enzymes and gene expression,increase the activity of antioxidant enzymes,reduce lipid oxidation and decomposition,increase the net export of liver TG,and thus regulate blood lipid metabolism.It is worth noting that the effects of different doses of β-CM-7 are large,and the effects are not uniform in different systems.The specific regulatory mechanism is still unclear.Whether it has side effects on liver inflammation needs further verification. |
