Study on the Protective Effect of Modified Buyang Huanwu Decoction and Shenqi Dihuang Decoction on Mice with Diabetic Kidney Disease by Regulating VEGF-C/VEGFR3 Pathway and Inhibiting Lymphangiogenesis
Objective To explore the protective effect and mechanism of modified Buyang Huanwu Decoction and Shenqi Dihuang Decoction on diabetic kidney disease(DKD)mice based on the regulation of VEGF-C/VEGFR3 pathway inhibiting lymphangiogenesis.Methods Twenty-four male db/db mice were randomly divided into model group,Chinese medicine group(modified Buyang Huanwu Decoction combined with Shenqi Dihuang Decoction,crude drug 24.44 g·kg-1)and western medicine group(Irbesartan,13.5 mg·kg-1),with eight mice in each group.Eight db/m mice were selected as control group.Intragastric administration was given once a day for 12 consecutive weeks.Fasting blood glucose(FBG),total cholesterol(TC),triglyceride(TG),urinary albumin/creatinine ratio(ACR)and kidney index were measured.The pathological changes of renal tissue were observed by HE and Masson staining.The expressions of fibronectin(FN),type I collagen(Col I),Vimentin,α-smooth muscle actin(α-SMA),transforming growth factor-β1(TGF-β1),vascular endothelial growth factor receptor 3(VEGFR3),vascular endothelial growth factor-C(VEGF-C),lymphatic endothelial hyaluronic acid receptor 1(LYVE-1),podoplanin(PDPN),tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)in renal tissue were detected by immunohistochemistry.The protein expressions of Col I,Vimentin,α-SMA,TGF-β1,VEGFR3,VEGF-C,LYVE-1,TNF-α and IL-1β in renal tissue were detected by Western Blot.The mRNA expressions of FN,Col I,TGF-β1,VEGF-C,VEGFR3,TNF-α and IL-1β in renal tissue were detected by Real-time PCR.Results Compared with the control group,the levels of serum FBG,TG,TC,ACR and kidney index in the model group were significantly increased(P＜0.05).Glomerular hypertrophy,mesangial matrix increased,basement membrane thickening,cystic cavity narrowing,renal tubular epithelial cell degeneration and necrosis,interstitial infiltration of a large number of inflammatory cells,renal tubular atrophy;the level of renal fibrosis was significantly increased(P＜0.05).The protein expressions of FN,Col I,Vimentin,α-SMA,TGF-β1,VEGFR3,LYVE-1,TNF-α,IL-1β in renal interstitium,the expression of VEGF-C protein in cytoplasm and the expression of VEGFR3 and PDPN protein around renal tubular capillaries were significantly up-regulated(P＜0.05).The protein expressions of Col I,Vimentin,α-SMA,TGF-β1,VEGFR3,VEGF-C,LYVE-1,TNF-α and IL-1β in renal tissue were significantly up-regulated(P＜0.05).The mRNA expression levels of FN,Col I,TGF-β1,VEGF-C,VEGFR3,TNF-α and IL-1β in renal tissue were significantly increased(P＜0.05).Compared with the model group,the levels of serum TG,TC and ACR in the Chinese medicine group were significantly decreased(P＜0.05).Renal tissue injury was improved to varying degrees,renal inflammatory cell infiltration was reduced to a certain extent,and renal tissue fibrosis was significantly reduced(P＜0.05).The protein expressions of FN,Col I,Vimentin,α-SMA,TGF-β1,VEGFR3,LYVE-1,TNF-α,IL-1β in renal interstitium,the protein expression of VEGF-C in cytoplasm and the protein expressions of VEGFR3 and PDPN around renal tubular capillaries were significantly down-regulated(P＜0.05).The protein expressions of Col I,Vimentin,α-SMA,TGF-β1,VEGFR3,VEGF-C,LYVE-1,TNF-α and IL-1β in renal tissue were significantly down-regulated(P＜0.05).The mRNA expression levels of FN,Col I,TGF-β1,VEGF-C,VEGFR3,TNF-α and IL-1β in renal tissue were significantly decreased(P＜0.05).Conclusion Modified Buyang Huanwu Decoction combined with Shenqi Dihuang Decoction can reduce the level of inflammation and fibrosis in renal tissue of DKD mice,and its mechanism may be related to the regulation of VEGF-C/VEGFR3 pathway to inhibit lymphangiogenesis.
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