ABSTRACT
BACKGROUND: Diabetic kidney disease (DKD) is a secondary complication of diabetes mellitus and a leading cause of chronic kidney disease. AIM: To investigate the impact of long-term canagliflozin treatment on DKD and elucidate its underlying mechanism. METHODS: DKD model was established using high-fat diet and streptozotocin in male C57BL/6J mice (n = 30). Mice were divided into five groups and treated for 12 weeks. 1) normal control mice, 2) DKD model, 3) mice treated low-dose of canagliflozin, 4) high-dose of canagliflozin and 5) ß-hydroxybutyrate. Mice kidney morphology and function were evaluated, and a metabolomics analysis was performed. RESULTS: Canagliflozin treatment reduced blood creatinine and urine nitrogen levels and improved systemic insulin sensitivity and glucose tolerance in diabetic mice. Additionally, a decrease in histological lesions including collagen and lipid deposition in the kidneys was observed. ß-hydroxybutyrate treatment did not yield a comparable outcome. The metabolomics analysis revealed that canagliflozin induced alterations in amino acid metabolism profiles in the renal tissue of diabetic mice. CONCLUSION: Canagliflozin protects the kidneys of diabetic mice by increasing the levels of essential amino acids, promoting mitochondrial homeostasis, mitigating oxidative stress, and stimulating the amino acid-dependent tricarboxylic acid cycle.
Subject(s)
Diabetes Mellitus, Experimental , Diabetic Nephropathies , Sodium-Glucose Transporter 2 Inhibitors , Animals , Male , Mice , 3-Hydroxybutyric Acid/therapeutic use , Amino Acids , Canagliflozin/pharmacology , Canagliflozin/therapeutic use , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/metabolism , Diabetic Nephropathies/drug therapy , Diabetic Nephropathies/prevention & control , Diabetic Nephropathies/etiology , Kidney/pathology , Mice, Inbred C57BL , Sodium-Glucose Transporter 2 Inhibitors/pharmacology , Sodium-Glucose Transporter 2 Inhibitors/therapeutic useABSTRACT
OBJECTIVE: To evaluate the efficacy of adductor canal block (ACB) combined with transcutaneous electrical acupoint stimulation (TEAS)for postoperative analgesia and early functional exercise after total knee arthroplasty (TKA). METHODS: A total of 84 patients underwent primary unilateral TKA from January 2019 to August 2020 were selected, including 45 males and 39 females, aged 66-77 (72.8±8.9) years;body mass index (BMI) was for 19-25 (23.6±3.5) kg /m2. They were divided into adductor canal block combined with transcutaneous electrical acupoint stimulation group (TEAS+ACB group)and simple adductor canal block group (ACB group) according to random number table method, 42 cases in each group. ACB was performed in ACB group during the operation. And TEAS was performed in TEAS+ACB group on bilateral lower limbs in 1-7 days postoperative on the basis of ACB. VAS scores at 6, 12, 24, 48, 72 h after surgery, knee function at 1, 2, 3, 7 days after surgery, knee motion at 7 days after surgery and length of hospitalization days were recorded and compared between the two groups. RESULTS: There were no significant differences in VAS of rest pain and activity pain in postoperative 6, 12 h between two groups (P>0.05), but the VAS of TEAS+ACB group was lower at 24, 48, 72 h after surgery(P<0.05). There was no significant difference in at 1 day postoperatively between two groups(P>0.05) , but the knee function of TEAS+ACB group was better than that of the ACB group in 2, 3, 7 days postoperatively (P<0.05). The length of hospitalization days in were less than in ACB group. On the 7th day after operation, the knee motion of TEAS+ACB group was greater than that of the ACB group (P<0.05). CONCLUSION: TEAS combined with ACB has a better postoperative analgesic efficacy than simple ACB, and can promote early functional exercise of patients. It is safe and effective for postoperative analgesia after TKA.