芪黄固肾通络方调控PPARγ/CD36/NLRP3通路对糖尿病肾病小鼠足细胞炎症和脂质积累的影响OA

Objective To explore the potential mechanism of Qihuang Gushen Tongluo Prescription in improving podocyte inflammation and lipid accumulation in diabetic nephropathy mice by regulating the PPARγ/CD36/NLRP3 pathway.Methods Male C57BL/6J mice were selected as the experimental subjects.A diabetic nephropathy mouse model was induced by a high-fat and high-sugar diet combined with intraperitoneal injection of streptozotocin.After successful modeling,the mice were divided into normal group,model group,GW9662 group,and Qihuang Gushen Tongluo Prescription low-,medium-,and high-dosage groups,with 7 mice in each group.After continuous intragastric administration for 12 weeks,fasting blood glucose,24-hour urine protein,serum creatinine(SCr),and blood urea nitrogen(BUN)contents were detected,HE,PAS and Masson staining were used to observe renal pathological damage,glycogen deposition and renal fibrosis;Oil Red O staining was used to observe lipid accumulation,immunohistochemical staining was used to detect the expression of Podocin and Nephrin,immunohistochemical staining and Western blot were used to detect the expressions of Podocin,Nephrin,PPARγ,CD36,NLRP3,IL-1β and IL-18 proteins.Results Compared with the normal group,the fasting blood glucose,24-hour urine protein,SCr and BUN contents of the mice in model group significantly increased(P<0.01);the glomerular capillary tufts were atrophied,glycogen deposition increased,and the degree of fibrosis was aggravated,lipid accumulation was severe,the positive expressions of podocyte injury markers Podocin and Nephrin in renal tissue significantly decreased(P<0.01),and the expressions of PPARγ,CD36,NLRP3,IL-1β and IL-18 proteins significantly increased(P<0.01).Compared with the model group,the fasting blood glucose,24-hour urine protein,SCr and BUN contents of the Qihuang Gushen Tongluo Prescription groups and the GW9662 group all significantly decreased(P<0.01);glycogen deposition was reduced,fibrosis and lipid accumulation were alleviated,positive expressions of Podocin and Nephrin significantly increased,and protein expressions of PPARγ,CD36,NLRP3,IL-1β and IL-18 significantly decreased(P<0.05,P<0.01).Conclusion Qihuang Gushen Tongluo Prescription can effectively improve renal injury in diabetic nephropathy mice,and its mechanism may be related to regulating the PPARγ/CD36 signaling pathway,inhibiting NLRP3 inflammasome activity,and reducing podocyte inflammation and lipid accumulation in the kidneys.