| Objective: To explore the effect of aerobic exercise on the kidney of type 2 diabetic mice based on TGF-? / Smad signal transduction;to explore the effect of glucose and lipid metabolism on the kidney;to further explore the effect of aerobic exercise on the prevention and treatment of diabetic nephropathy and related mechanisms;to provide reference for the application of exercise therapy in the prevention and treatment of related diseases in the future To provide theoretical and experimental data support for clinical promotion.Methods: 20 healthy ob/ob male mice and 20 C57 male mice of 4 weeks of age were selected;they were randomly divided into OB aerobic exercise group(OS group,n=10)and C57 aerobic exercise group(CS group,n=10),OB blank control group(OD group,n=10),C57 blank control group(CD group,n=10).The OD group and CD group did not interfere.The OS group and CS group performed swimming training: rest 1 day a week,and swimming for the remaining 6 days;each training lasted 45 minutes.The body weight of each group of mice was measured on the rest day of each week,and one mouse was randomly selected from each cage for the abdominal glucose tolerance test(each group consists of 2 cages).After 18 weeks of aerobic exercise intervention,the mouse was anesthetized by intraperitoneal injection of anesthetic,and the eyeballs were removed for blood,and then the mouse kidneys and other tissues were sacrificed.Use HE staining and MASSON staining techniques to observe the changes in kidney tissue structure.Western-bolting was used to detect the expression of TGF-?1,Smad3,Smad7 and protein in the kidney tissues of the four groups of mice.ELISA technique was used to detect the serum fat content of mice in each group.Result:1.Results of body weight,renal weight index and blood glucose related indicators:After 18 weeks of aerobic exercise intervention,there was no significant difference in the weight gain of mice between the OS group and the OD group(P>0.05),and the weight change between the CS group and the CD group There was no significant difference(P>0.05).The kidney weight index of the mice in the OS group and the OD group was significantly higher than that of the CS group and the CD group(P<0.01),and the kidney weight index of the mice in the OS group was significantly lower than that of the OD group(P<0.05).The fasting blood glucose level of OS group mice was3.742.17mmol/L lower than that of OD group mice(P<0.01),and fasting blood glucose was significantly improved;the fasting blood glucose level of CS group mice was lower than that of CD group mice-1.33±4.38 mmol/L(P>0.05)The fasting blood glucose value did not change significantly.Compared with the OD group,the IPGTT-AUC of the mice in the OS group decreased by 543±334.2(P<0.05).After aerobic exercise intervention in C57 mice,there was no statistically significant difference between the IPGTT-AUC value of the CS group at the 18 th week and the CD group's IPGTT-AUC at the 18 th week(P=0.54,P>0.05).2.Biochemical indicators: After 18 weeks of aerobic exercise intervention,the measured LDL,T-CHO,TG,NEFA in the OD group were significantly higher than those in the OS group(P<0.01),and HDL was significantly lower than in the OS group(P<0.01).Between CS group and CD group: The LDL,T-CHO,TG,NEFA Ameasured in the CD group were significantly higher than those in the CS group(P<0.01),and HDL was significantly lower than the CS group(P<0.01).3.Western Blotting detected the expression of target protein in kidney tissue: After 18 weeks of aerobic exercise intervention,between the OS group and the OD group: the TGF-?1 protein expression in the OS group was significantly lower than that in the OD group,and the difference was statistically significant(P<0.05);the expression of Smad3 protein in the OS group was significantly lower than that of the OD group,and the difference was statistically significant(P<0.01);the expression of Smad7 protein in the OS group was significantly higher than that of the OD group(P<0.01).Between CS group and CD group;TGF-?1 protein expression in CS group was significantly lower than that in CD group(P<0.05);Smad3 protein expression in CS group was significantly lower than CD group(P<0.01);Smad7 protein expression in CS group All were significantly higher than the CD group(P<0.01).4.The histological changes in the kidneys of each group of mice: HE staining results:ob/ob mouse kidneys all showed interstitial inflammatory cell infiltration,mainly lymphocytes,and fibrous tissue proliferation;after 18 weeks of aerobic exercise intervention,OS Compared with the kidney tissue of the OD group,the kidney tissue of the mice in the OD group had significantly fewer inflammatory cells and less fibrous tissue proliferation.There was no glomerular swelling and renal tubular epithelial cell swelling.MASSON staining results;ob/ob mouse kidney tissues have different degrees of fibrosis and degeneration.After 18 weeks of aerobic exercise intervention,it can be seen between the OS group and the OD group: the degree of renal fibrosis in the OS group was significantly lighter than that in the OD group.Conclusion:1.After four weeks of age,the fasting blood glucose of ob/ob mice was higher than11.1mmol/L,and the abdominal glucose tolerance AUC and body weight gain were significantly higher than C57 mice,which proved that ob/ob mice type 2 diabetes model modeling success.2.18 weeks of aerobic exercise training can significantly improve the blood glucose metabolism of ob/ob mice,and the longer the training period,the more significant the effect;but there is no significant effect on the blood glucose of normal mice.3.18 weeks of aerobic exercise can significantly improve the fat metabolism of ob/ob mice and C57 mice.Among the five indicators of blood lipids,TG and NEFA normal mice improved more significantly;this may indicate that exercise may improve the blood lipid indicators related to insulin resistance,and the preventive effect may be better than the therapeutic effect.4.The 18-week aerobic swimming exercise had no significant effect on the weight gain of ob/ob mice and c57 mice aged 4-22 weeks.?5.18-week aerobic exercise intervention can down-regulate the expression of TGF-?1and Smad3 protein and up-regulate the expression of Smad7 protein to improve the inflammatory response of kidney tissue cells by inhibiting the TGF-?/Smad signaling pathway in the kidney tissue of C57 and ob/ob mice.The degree of fibrosis,thereby protecting the kidneys.In summary,prolonged aerobic exercise can significantly improve blood lipid metabolism in ob/ob mice and significantly improve fat metabolism in C57 mice.In addition,aerobic exercise can significantly protect the kidneys by inhibiting the TGF-?/Smad signaling pathway in the kidney tissues of C57 and ob/ob mice,and can significantly delay the process of diabetic nephropathy. |
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