Objective:Renal microvascular injury,as the result of diabetic toxicity,plays a vital role in the pathogenesis of diabetic kidney disease(DKD)during diabetes progression.Here,we investigated whether electroacupuncture...Objective:Renal microvascular injury,as the result of diabetic toxicity,plays a vital role in the pathogenesis of diabetic kidney disease(DKD)during diabetes progression.Here,we investigated whether electroacupuncture(EA)could ameliorate renal microvascular impairment to prevent DKD and its underlying mechanism.Methods:The male db/db mice with Leprdb mutation were used as the model of type 2 diabetes mellitusinduced DKD and treated with EA at"Zusanli(ST36)"and"Weiwanxiashu(EX-B3)"acupoints for 4 weeks.Age-matched wild-type mice were used as control group.Renal protection of EA was evaluated by mouse urine production,water consumption,renal index and tubules dilation.Two-photon microscope imaging was applied to visualize renal microvascular blood flow in vivo.Immunostaining and western blot analysis were used to detect the glomerular alternations and inflammatory signaling.Results:EA significantly attenuated renal dysfunction in db/db mice.The protective effect of EA on renal microvascular recovery was observed both in function and structure analysis.Firstly,EA restored the renal microvascular blood flow in db/db mice.Then,glomerular hypertrophy and glomerular barrier destruction were suppressed after EA,as respectively demonstrated by the reduction of glomerular dilation,Collagen IV and Claudin-1 deposits.In mechanism,EA suppressed the diabetes-induced inflammatory response in renal microvessels,presenting as the downregulation of inflammatory cytokines interleukin-1β(IL-1β)and tumor necrosis factor(TNF-α),intercellular cell adhesion molecule-1(ICAM-1)activation,and macrophage infiltration after EA treatment.Conclusion:These findings indicated the benefits of EA against renal microvascular impairment and DKD progression,which was associated with the action of anti-inflammation,and supported EA as a promising modality for DKDmanagement.展开更多
基金Supported by National Natural Science Foundation of China:82274628Natural Science Foundation of Guangdong Province:2023A1515030167Discipline Collaborative Innovation Team Program of Double First-class and High-level Universities for Guangzhou University of Chinese Medicine:2021XK01。
文摘Objective:Renal microvascular injury,as the result of diabetic toxicity,plays a vital role in the pathogenesis of diabetic kidney disease(DKD)during diabetes progression.Here,we investigated whether electroacupuncture(EA)could ameliorate renal microvascular impairment to prevent DKD and its underlying mechanism.Methods:The male db/db mice with Leprdb mutation were used as the model of type 2 diabetes mellitusinduced DKD and treated with EA at"Zusanli(ST36)"and"Weiwanxiashu(EX-B3)"acupoints for 4 weeks.Age-matched wild-type mice were used as control group.Renal protection of EA was evaluated by mouse urine production,water consumption,renal index and tubules dilation.Two-photon microscope imaging was applied to visualize renal microvascular blood flow in vivo.Immunostaining and western blot analysis were used to detect the glomerular alternations and inflammatory signaling.Results:EA significantly attenuated renal dysfunction in db/db mice.The protective effect of EA on renal microvascular recovery was observed both in function and structure analysis.Firstly,EA restored the renal microvascular blood flow in db/db mice.Then,glomerular hypertrophy and glomerular barrier destruction were suppressed after EA,as respectively demonstrated by the reduction of glomerular dilation,Collagen IV and Claudin-1 deposits.In mechanism,EA suppressed the diabetes-induced inflammatory response in renal microvessels,presenting as the downregulation of inflammatory cytokines interleukin-1β(IL-1β)and tumor necrosis factor(TNF-α),intercellular cell adhesion molecule-1(ICAM-1)activation,and macrophage infiltration after EA treatment.Conclusion:These findings indicated the benefits of EA against renal microvascular impairment and DKD progression,which was associated with the action of anti-inflammation,and supported EA as a promising modality for DKDmanagement.