益元饮通过下调TGF-β1/PI3K/Akt信号通路治疗糖尿病肾病的作用机制OA

Objective To investigate the mechanism of action by which Yiyuan Drink treats diabetic kidney disease(DKD)by regulating the transforming growth factor-β1(TGF-β1)/phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)signaling pathway.Methods Seventy-five SPF male Wistar rats were randomly divided into five groups:control group,model group,Yiyuan Drink group(23.52 g·kg-1·d-1),pancreatic kininogenase tablets group(36 U·kg-1·d-1),and Zhenwu Decoction group(4.2 g·kg-1·d-1),with 15 rats in each group.Except for the control group,the remaining rats were fed with a high-sugar and high-fat diet for 4 weeks,followed by intraperitoneal injection of streptozotocin(STZ,30 mg·kg-1·d-1)to establish the DKD model.Treatments were administered for 8 successive weeks.The general conditions of rats in each group were observed.Renal histopathological changes were examined by HE and Masson staining.Random blood glucose(GLU),24-hour urinary protein(24 hUTP),and urinary albumin-to-creatinine ratio(UACR)in each group were measured.Western blot analysis was performed to test the expression levels of TGF-β1,PI3K,Akt,phosphorylated PI3K(p-PI3K),phosphorylated Akt(p-Akt),and fibronectin(FN)in renal tissues.Results Rats in the control group exhibited good overall conditions,including normal mental state,appetite,activity levels,water intake,and excretion.Rats in the model group exhibited lethargy,lusterless hair,and polydipsia,polyphagia,and polyuria.Rats in the Yiyuan Drink group showed significant improvement in mental state,activity levels,and responses to external stimuli;their water intake and urine output were reduced compared to the model group,and their body weight increased steadily.Rats in the kininogenase tablet group showed relatively good recovery in mental state and activity levels.Rats in the Zhenwu Decoction group were relatively active but still exhibited a tendency to lie down and appeared lethargic,with sluggish responses to external stimuli.Histopathological examination revealed that rats in the control group had regular glomerular morphology and minimal collagen deposition in the renal interstitium.In contrast,rats in the model group showed marked mesangial matrix proliferation,tubular epithelial cell edema,and massive collagen deposition in the renal interstitium by week 8.The Zhenwu Decoction group showed moderate recovery,while the Yiyuan Drink and the pancreatic kininogenase tablets groups showed improved renal morphology and reduced renal interstitial fibrosis.Compared with the control group,rats in the model group exhibited reduced body weight(P＜0.05),elevated GLU levels(P＜0.05),increased 24-hUTP levels(P＜0.05),and elevated UACR(P＜0.05),along with significantly upregulated expressions of TGF-β1,p-PI3K,p-Akt,and FN(P＜0.01)in renal tissues.Compared with the model group,all treatment groups exhibited increased body weight(P＜0.05),decreased renal hypertrophy index(P＜0.05),reduced 24-h UTP and UACR levels(P＜0.05).Furthermore,all treatment groups significantly suppressed TGF-β1 expression(P＜0.01)and reduced the phosphorylation levels of PI3K and Akt(P＜0.05,P＜0.01),while simultaneously downregulating the expression levels of the FN protein(P＜0.05,P＜0.01).Compared with the Zhenwu Decoction group,the pancreatic kininogenase tablets group showed decreased levels of 24-h UTP and UACR(P＜0.05).In the Yiyuan Drink group,body weight increased(P＜0.05),while the levels of 24-h UTP and UACR were reduced(P＜0.05).The degree of improvement in the afore-mentioned indicators in the Yiyuan Drink group was comparable to that in the Pancreatin kininogenase tablets group(P＞0.05).Conclusion Yiyuan Drink can reduce GLU levels,improve renal function,and alleviate pathological damage in DKD rats,thereby delaying the progression of DKD.Its underlying mechanism of action may be related to inhibiting the activation of the TGF-β1/PI3K/Akt signaling pathway.