Effect and Mechanism of Buyang Huanwutang(补阳还五汤)on Nrf2/HO-1 Pathway in Diabetic Kidney Disease Mice
Objective:To explore whether Buyang Huanwutang(补阳还五汤)inhibits oxidative stress in diabetic kidney disease(DKD)mice by regulating nuclear transcription factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)pathway,to alleviate kidney tissue damage and delay kidney fibrosis.Methods:A total of 73 C57BL/6 mice were randomly divided into model group(n=63)and normal control group(n=10).Mice in model group were fed with high-sugar and high-fat diet for 6 weeks,and after intraperitoneal injection of 50 mg/kg streptozoto-cin(STZ)for 5 days,and then,they were continuously given high-sugar and high-fat diet for 8 weeks.When the mice showed positive urine protein,DKD model was successfully prepared.The DKD mice were randomly divided into model control group,rosiglitazone 7.05×10-4 g/kg group,and Buyang Huanwutang 3.21,6.41 and 12.82 g/kg groups.Mice in all groups were given corresponding drugs or normal saline,once per day for 8 consecutive weeks.During the drug intervention period,the body mass,blood glucose,urine volume and 24-hour urinary total protein quantity(24 h-UTP)of the mice were monitored.After administration,Masson staining and Periodic Acid-Schiff(PAS)staining were used to observe the pathological changes in mouse kidney tissue.The activities of superoxide dismutase(SOD)and catalase(CAT)were measured.The expression of reactive oxygen species(ROS)in mouse kidney tissue was detected by fluorescence probe labeling,and the protein expressions of transforming growth factor β1(TGF-β1),α-smooth muscle actin(α-SMA),fibronectin(FN),collagen Ⅰ(Col Ⅰ),Nrf2 and HO-1 were detected by Western blot.Results:Compared with the normal control group,the model group had decreased body mass,increased blood sugar,elevated urine volume and 24 h-UTP,thickened glomerular capsule wall,significant collagen fibrous dysplasia,mesang-ial hyperplasia in the glomerulus,deposition of glycogen particles around the glomerulus,reduced activities of SOD and CAT,enhanced expres-sion of ROS,down-regulated expressions of Nrf2 and HO-1,and up-regulated expressions of TGF-β1,α-SMA,FN and Collagen Ⅰ(P＜0.05 or P＜0.01).Compared with the model control group,mice in Buyang Huanwutang groups and rosiglitazone group gained weight,and their blood sugar,urine volume and 24 h-UTP were decreased.The pathological damage of kidney tissue was improved to varying degrees,and the activities of SOD and CAT were increased.Additionally,the expressions of Nrf2 and HO-1 was up-regulated,while the expressions of ROS as well as TGF-β1,α-SMA,FN,and Collagen Ⅰ were down-regulated(P＜0.05 or P＜0.01).Conclusion:Buyang Huanwutang can inhibit oxi-dative stress by activating Nrf2/HO-1 pathway,thus alleviating kidney fibrosis in DKD mice and relieving the pathological damage.
万方数据
维普
