Study On The Effect Of Milk-derived ?-casomorphin-7 On Renal Function And Mechanism In Aging Mice

ObjectiveMilk-derived ?-casomorphin-7(BCM-7)is released by casein and is present in most dairy products.Early studies have shown that BCM-7 can prevent and protect diabetes by reducing oxidative stress and protect kidney function induced by high glucose.This study aimed to investigate the effects of BCM-7 at different doses on the changes of renal function induced by natural aging and the relationship between them to provides more theoretical reference for revealing the effect of BCM-7 on health and renal function.MethodTwo-month-old(12 young mice)and 11-month-old(48 aged mice)male Kunming mice were selected.After one week of adaptive feeding,the mice were fed with a normal diet,normal body temperature,normal stool,and normal activities.Senescent mice were randomly divided into three groups according to their body weight,which was divided into the low-dose group(BCM-7 0.2×10-6 mol/L),medium-dose group(BCM-7 1×10-6 mol/L),and high-dose group(BCM-75×10-6 mol/L),and was given 0.5 mL of BCM-7 solution once a day.The aging control group(0.5 mL/d of normal saline)and the young blank control group(0.5 mL/d of normal saline)were used.Observe and record the physiological activities,diet,physical changes,and so on.Weigh the mice once a week.During ether anesthesia,blood was extracted from the eyeball rapidly,and the supernatant was stored at-20?.Kidney and spleen samples were collected and stored in a-70? refrigerator.The renal tissue supernatant and serum were taken to detect the changes in renal function,inflammatory and oxidation stress.Finally,Canonical correlation analysis(CCA)and principal component analysis(PCA)were used to find out the main influencing factors and their relationship between renal function and inflammatory and oxidative stress.Results(1).Effects of ?-casomorphin-7 on basic physiological characteristics of aging mice:The weight of the low,middle,and high BCM-7 intervention group was lower than that of the aging control group,and the rate of weight gain decreased with the increase of the BCM-7 intervention dose.The bodyweight of mice in the aging control group and young mice increased by 1.22%and 6.63%respectively before and after one month.The kidney index and spleen index of the aging control group had no significant changes compared with the young mice.(2)Effects of ?-casomorphin-7 on renal function and hormones in aging mice:The content of BUN was significantly decreased in the aging control group(p<0.05)compared with young mice,while the content of CRE and Cys-C was significantly increased in the aging control group(p<0.01).The Cys-C content of mice in the medium-dose group was significantly lower than that in the aging control group(p<0.01).However,there was no significant difference between CK and ACTH aging control group and the BCM-7 intervention group.(3).Effects of ?-casomorphin-7 on the levels of cytokines and related proteins in the kidney of aging mice:The sIgA content of the aging control group was significantly increased(p<0.01)compared with the young mice.The sIgA content of the BCM-7 group was in direct proportion to the BCM-7 intervention dose,and the low dose of BCM-7 could significantly reduce the sIgA content of the aging mice(p<0.001).The levels of IL-6 and TGF-?1 in the aging control group decreased significantly(p<0.05)compared with the young mice.In the BCM-7 intervention group.High dose BCM-7 could significantly increase IL-1? and CRP levels in aging mice compared with the aging control group(p<0.05)(4).Effects of ?-casomorphin-7 on oxidative stress in the kidney of aging mice:The content of GSH-PX in the high-dose BCM-7 intervention group was much higher than that in the aging control group(p<0.05).No significant difference was found among the groups with T-AOC,SOD,and MDA.(5).Correlation analysis of ?-casomorphin-7 on renal function between inflammatory stress and oxidative stress in aging mice:CRE and sIgA were negatively correlated with TGF-?1(r=-0.47;r=-0.37),while IL-6 was correlated with CRE and CK(r=-0.47;r=+0.38).There was a negative correlation between SOD and Cys-C(r=-0.32).IL-6 and TNF-? were the main markers of inflammatory stress.In the canonical variable set(U2,V2),CRE and CK have similar and larger canonical correlation coefficients(r=-0.71;r=-0.769),T-AOC is the largest variable in the V2 variable,then MDA.The characteristic analysis of principal component-related matrix loads between renal function and inflammatory stress showed that TGF-?1(0.50),IL-6(-0.48),and CRE(0.48)contributed significantly to renal function.The analysis of the correlation matrix load between renal function and oxidative stress shows that T-AOC has the greatest influence on the set of variables,followed by CK,SOD,GSH-PX.ConclusionNatural aging led to weight loss and renal function changes in mice,and medium doses of BCM-7 improved glomerular filtration function.High-dose BCM-7 can reduce the oxidative stress in the kidney of aging mice to some extent.Both PCA and CCA can effectively,intuitively,and consistently analyze the relationship between renal function and inflammatory and oxidative stress in aging mice,it is speculated that low and moderate doses of BCM-7 can improve renal function in aging mice,thereby increasing the secretion of anti-inflammatory factors and raising the level of Superoxide dismutase,thus may regulate the body to reduce the production of inflammation and alleviate the harm of oxidative stress.s.