固肾泄浊和络方对糖尿病肾病大鼠肾脏的保护作用及对NF-κB/Wnt/β-catenin信号通路的影响OA

Objective It is to investigate the protective effect of Gushen Xiezhuo Heluo prescription on the kidney of rats with diabetic kidney disease and its effect on nuclear factor kappa-B(NF-κB)/Wnt/β-catenin pathways.Methods Seventy-two male SD rats were taken,12 of which were randomly selected as normal group,and the remaining 60 rats were given 1%streptozotocin(STZ)solution by a single intraperitoneal injection into the left side to establish models of diabetic kidney disease.50 successfully model rats were randomly divided into model group,irbesartan group,low-dose,medium-dose and high-dose groups of Gushen Xiezhuo Heluo prescription,with 10 rats in each group.The irbesartan group was ad-ministered irbesartan via gastric gavage at a dose of 0.0781 g/kg,while the low-dose,medium-dose and high-dose groups of Gushen Xiezhuo Heluo prescription were administered the formula solution via gastric gavage at concentrations of 0.53 g/mL,1.06 g/mL,and 2.11 g/mL,respectively,the control group and normal group were administered normal saline via gavage,all once daily,continuously treated for 6 weeks.The general condition of the rats was observed,their body weight,random blood glucose,and 24-hour urine protein(24hUP)were measured before the first gavage and after the final gavage,the se-rum levels of creatinine(SCr)and blood urea nitrogen(BUN)were measured after the final gavage;the renal tissue pa-thology was observed by HE staining and PAS staining;the mRNA and protein expressions of NF-κB,type Ⅳ collagen,Wnt4,β-catenin,matrix metalloproteinase(MMP)-7,and MMP-3 in renal tissue were detected by qPCR and Western blot assays,respectively.Results Compared with the normal group,the body weight of rats in the model group was decreased(P<0.05),their random blood glucose,SCr,BUN and 24hUP were significantly increased(all P<0.05);the patholog-ical changes such as thickened basement membrane,increased mesangial matrix,infiltration of interstitial cells and renal fi-brosis were found;the mRNA and protein expressions of NF-κB,type Ⅳ collagen,Wnt4,β-catenin,MMP-7 and MMP-3 in renal tissue were increased(all P<0.05).Compared with the model group,the body weights of rats in the medium-dose and high-dose groups of Gushen Xiezhuo Heluo prescription and irbesartan group were decreased(all P<0.05),their random blood glucose,SCr,BUN and 24hUP were significantly decreased(all P<0.05);the mesangial matrix was de-creased,the infiltration of interstitial cells and renal fibrosis were alleviated;the mRNA and protein expressions of NF-κB,type Ⅳ collagen,Wnt4,β-catenin,MMP-7 and MMP-3 in renal tissue were decreased(all P<0.05),and the improve-ments of these indicators except for the body weight,random glucose,SCr and BUN in the high-dose group of Gushen Xiezhuo Heluo prescription were more significant than those in the other medicated groups(all P<0.05).Conclusion Gushen Xiezhuo Heluo prescription can significantly alleviate renal dysfunction and renal fibrosis,and inhibit inflammatory responses in rats with diabetic nephropathy.It may exert its nephroprotective effects via regulating the NF-κB/Wnt/β-cate-nin signaling pathway,down-regulating the expressions of MMP-7 and MMP-3,and reducing the excessive deposition of type Ⅳ collagen.