Comparative Study On The Preventive And Therapeutic Effects Of Canagliflozin And Soy Isoflavone On Diabetes Nephropathy

Objective: To explore and compare the effects of sodium glucose cotransporter 2inhibitor(SGLT2i),Canagliflozin(CGLZ)and Soy isoflavone(SIF)on the prevention and treatment of nephropathy and anti osteoporosis in diabetes rats.Methods: Forty male SD rats were randomly divided into control group(NG),model group(MG),SIF medication group(SIG),low-dose CGLZ medication group(LCG),high-dose CGLZ medication group(HCG),with 8 rats in each group.MG and each medication group were intraperitoneally injected with streptozotocin for modeling.The rats in drug groups were treated by intragastric administration once a day for 12 weeks respectively.Body mass,food intake,and water consumption were detected one day before and immediately after drug intervention.Blood glucose was measured one day before drug intervention and at the end of the 4th,8th,and 12 th weeks after drug intervention.At the end of the 12 th week,a fully automated blood biochemical analyzer was used to detect Serum albumin(ALB),serum calcium(Sca),serum phosphorus(SP),serum K(SK),serum Na(Sna),serum Cl(Scl),serum creatinine(Scr),urea nitrogen(Urea),serum uric acidserum(Sua),Cystatin C(Cys C),β2Microglobulin(β2-M),urine protein(Pro),urine creatinine(Ucr),urine protein/urine creatinine ratio(UPCR)and 25 hydroxyvitamin D(25-OH-D3).At the end of the 12 th week,HE staining method was used for renal histopathology analysis,and dual energy X-ray bone densitometer was used to detect bone metabolism related indicators including total bone mineral density(TBMD),regional bone mineral density(RBMD)(detection of local areas including head,upper limb,thigh,trunk,rib,pelvis and spine),total body salt content(TBSC),total body fat mass(TBFM)and total body muscle mass(TBMM)in vivo.Results:(1)After 12 weeks of successful modeling,the MG,SIG,LCG,and HCG groups significantly increased their water consumption and food intake compared to the NG group,while their body masses decreased(P<0.01).The body masses of LCG and HCG groups significantly increased compared to MG group and HCG group significantly increased compared to SIG group(P<0.05 or 0.01).(2)After the 4th week of drug intervention,the FPG of the LCG and HCG groups decreased compared to the MG group,and after the 8th and 12 th weeks of drug intervention,the FPG of the SIG,LCG,and HCG groups decreased compared to the MG group(P<0.01).At the 4th,8th,and 12 th weeks of drug intervention,the medication groups were compared between groups.The LCG and HCG groups showed a more significant decrease in FPG compared to the SIG group,and the HCG group showed a more significant decrease in FPG compared to the LCG group(P<0.01).the therapeutic effect was HCG>LCG>SIG in turn.(3)After the 4th,8th,and 12 th weeks of drug intervention,Pro,Ucr,and UPCR of rats in each medication group significantly decreased compared to the MG group(P<0.01).There was no statistically significant difference in urine indicators between the medication groups(P>0.05).(4)After 12 weeks of drug intervention,compared with the MG group,the ALB levels in the SIG,LCG,and HCG groups increased(P<0.05 or0.01);Scr、Urea、SUA、CYS-C、β2-M and SK levels in the SIG,LCG,and HCG groups decreased significantly(P<0.05 or 0.01);The Scl level in the SIG group decreased(P<0.05);The level of 25-OH-D3 in the HCG group increased(P<0.01).Comparison between medication groups showed that the levels of 25-OH-D3 in the HCG group were higher than those in the SIG and LCG groups(P<0.05 or 0.01).(5)After 12 weeks of drug intervention,the MG group showed an increase in glomerular volume,dilation of Bowman’s capsule,thickening of capsule walls,and a large number of eosinophilic masses visible in the capsule cavity.The mesangial matrix in the glomerulus proliferated extensively,and lymphocytes infiltrated;A large number of renal tubules have decreased in volume,with irregular arrangement of epithelial cells in the renal tubules,visible watery degeneration of cells,loose and light staining of cytoplasm,and even necrosis,nuclear pyknosis,and brush like edge detachment;Renal interstitial edema with inflammatory exudation.The above pathological damage in SIG,LCG,and HCG groups has been improved to varying degrees.(6)After 12 weeks of drug intervention,compared with the MG group,only the HCG group showed a statistically significant increase in TBSC(P<0.05),while the differences in TBMD,TBSC,TBFM,and TBMM of SIF and the LCG groups were not statistically significant(P>0.05);The thigh of the HCG group,the trunk,rib,and spine of the LCG and HCG groups,and the pelvis of the SIG and HCG groups all showed an increase in bone density(P<0.05).Compared between medication groups,the TBMD of the HCG group increased compared to the SIG and LCG groups(P<0.05),while the TBSC of the HCG group increased compared to the SIG group and the thigh bone density increased compared to the LCG group(P<0.05 or 0.01).Conclusion:(1)Both low and high doses of CGLZ can reduce the FPG,SUA,Scr,Urea,CYS-C and β2-M levels of DM,increase serum ALB levels,and decrease urine Pro and UPCR levels.High dose CGLZ can also increase the serum 25-OH-D3 level of DM.The results of this study indicate that both low and high doses of CGLZ can improve hyperglycemia and renal damage in DM.(2)SIF can reduce FPG,SUA,Scr,Urea,CYS-C and β2-M level of DM,increase serum ALB level,reduce urine Pro and UPCR levels,and have the effect of preventing and treating DM and its renal damage(3)Compared with low-dose and high-dose CGLZ and SIF,the blood glucose regulation effect is HCG>LCG>SIG in turn,but there is no significant difference in the effectiveness of the three in improving diabetic kidney damage(4)Both low-dose and high-dose CGLZ and SIF can reduce the risk of fractures,and the therapeutic effect of high-dose CGLZ is superior to that of low-dose CGLZ and SIF.But the three have inconsistent effects on bone density in different regions.