| Objective: To compare the effects of swimming and treadmill exercise on improving diabetic kidney inflammation,and to explore the role of miR-146 a in improving diabetic kidney inflammation,so as to provide experimental evidence for aerobic exercise to improve diabetic kidney inflammation.Methods: 56 SD rats randomly selected only 12 as normal control group(NC group),with high fat,high sugar to feed the rest 14 weeks of rats,according to the weight by intraperitoneal injection of only chain urea with cephalosporins(STZ Streptozotocin,).Diabetic rats were randomly divided into three groups: diabetic model group(DM,12 rats),diabetic treadmill exercise group(MR,12 rats)and diabetic swimming exercise group(MS,12 rats).The rats in MR Group were given adaptive treadmill running for 3 days in advance,which was gradually increased to 15m/min(60min,0°).The rats were given continuous exercise for 8 weeks,once a day,and rested for 2 days on Saturdays and Sundays.In MS group,the rats were given adaptive swimming exercise for 3 days in advance,which was gradually increased to 60 min.The rats were given continuous exercise for 8 weeks,once a day,and rested for 2 days on Saturdays and Sundays.During this period,neither the NC group nor the DM group received any exercise intervention.The body weight and fasting blood glucose of each group were monitored at a fixed time and place every Sunday.After 8 weeks of aerobic exercise intervention,urine,blood and kidneys were collected in the morning,and the kidneys were washed and unwrapped,then weighed and divided.The expression levels of serum IL-1β,IL-6 and TNF-α inflammatory factors were measured by ELISA.The morphological changes of rat kidneys were observed by HE,PAS,Masson staining and transmission electron microscopy.Biochemical kit was used to analyze the protein/creatinine ratio(P/CR)in blood and urine of rats.The expression levels of inflammatory protein(AGE,TLR4,NF-κB)and caustic protein(NLRP3,Caspase-1,GSDMD-N)in kidney were detected by WB.The expression of miR-146 a in kidney was detected by q RT-PCR.Research results:1.General indicatorsBody weight: The body weight of NC group and DM group was significantly increased at 8 weeks compared with 0 weeks(P < 0.01).The body weight of DM group was significantly lower than that of NC group at 6 weeks and 8 weeks(P < 0.05 or P < 0.01).After 8 weeks of aerobic exercise intervention,the average body weight of rats in the MR And MS groups was higher than that in the DM group,but there was no significant difference.Blood glucose: Intra-group comparison: Fasting blood glucose in DM group increased significantly after week 4 compared with week 0(P < 0.05 or P < 0.01);At the 4th week of exercise intervention,blood glucose level in MR Group was significantly decreased compared with the 0 week(P < 0.05).Comparison between groups: From week 0 to week 8,fasting blood glucose in model group and exercise group was significantly higher than that in NC group(P < 0.01).Double kidney weight: The level of double kidney weight in DM and exercise groups was significantly higher than that in NC group(P < 0.01 or P < 0.05).After 8 weeks of aerobic exercise intervention,the double kidney weight in MR Group and MS group was significantly lower than that in DM group(P < 0.01 or P < 0.05).Renal coefficient: The level of renal coefficient in DM group and exercise group was significantly higher than that in NC group(P < 0.01).After 8 weeks of aerobic exercise intervention,the renal coefficient of MR Group and MS group was significantly lower than that of DM group(P < 0.01).2.Morphological indexesHE staining results: The morphology and structure of the glomeruli and tubules in NC group were complete and clear.In the DM group,glomeruli were enlarged,interstitial inflammatory cells infiltrated,glomeruli capsular cavity tightened significantly,renal tubules were dilated and swollen,vacuolar degeneration occurred in part,and wall space was enlarged.After 8 weeks of exercise intervention,the lesion degree of MR Group and MS group was significantly reduced compared with DM group.PAS staining results: There was no obvious purplish red glycogen deposition in NC group.Compared with NC group,PAS positive reaction was observed in some mesangial and basal membrane of renal tubules in DM group,and red glycogen granules were observed.After 8 weeks of aerobic exercise intervention,PAS positive reaction in the MR And MS groups had different degrees of recovery compared with the DM group.Masson staining results: The kidney tissue in NC group was basically normal,and the collagen fiber staining was normal.Compared with NC group,the glomerular basement membrane and renal interstitial collagen fibers in DM group were more blue-stained,and there was fiber hyperplasia(P < 0.01).After 8 weeks of aerobic exercise intervention,compared with the DM group,the glomerular and interstitial collagen fibers in the MR And MS groups became bluer(P < 0.01).Electron microscopy results: The structure of glomerular basement membrane in NC group was clear,uniform and smooth,and there was no obvious thickening.The foot process is evenly distributed and neatly arranged;Compared with the NC group,the basement membrane of the glomeruli in the DM group showed diffuse thickening,the structure was not clear,the foot process of the podiocytes was widely fused,and the foot process disappeared and increased.After the intervention of aerobic exercise for 8 weeks,the glomerular basement membrane of MR And MS groups showed segmental thickened,the thickness was significantly reduced,and the minority of podocytes were fused.3.Indicators of kidney injurySerum creatinine level of DM group was significantly higher than that of NC group(P <0.01).After 8 weeks of aerobic exercise intervention,the serum creatinine level in MR Group and MS group was significantly lower than that in DM group(P < 0.05).Urinary protein creatinine ratio: The urinary P/CR level ratio in DM group was significantly higher than that in NC group(P < 0.01).After 8 weeks of aerobic exercise intervention,urinary P/CR levels in the MR And MS groups were significantly lower than those in the DM group(P < 0.01).4.PCR indexResults of renal miR-146a: After 8 weeks of aerobic exercise intervention,the expression level of miR-146 a in the MR And MS groups was significantly higher than that in the DM group(P < 0.05).5.Circulating inflammatory factor ELISA indexThe expression levels of IL-1β,IL-6 and TNF-α in DM group were significantly higher than those in NC group(P < 0.01).After 8 weeks of aerobic exercise intervention,the expression levels of IL-1β,IL-6 and TNF-α in MR And MS groups were significantly lower than those in DM group(P < 0.05 or P < 0.01).6.WB index of kidneyThe protein expression levels of AGE,TLR4,NF-κB,NLRP3,Caspase-1 and GSDMDN in DM group were significantly higher than those in NC group(P < 0.01).After 8 weeks of aerobic exercise intervention,the protein expression levels of AGE,TLR4,NF-κB,NLRP3,Caspase-1 and GSDMD-N in MR And MS groups were significantly lower than those in DM group(P < 0.05 or P < 0.01).There was no significant difference in GSDMD protein among all groups.Research conclusion:1.Swimming and treadmill running can improve renal tissue inflammation in diabetic rats by reducing scorch death,and there is no significant difference between them.2.The protective effect of swimming and treadmill exercise on the kidney of diabetic rats may be related to the increased expression of miR-146 a and decreased expression of TLR4/NF-κB in the kidney,which inhibit the inflammatory response. |
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