Background:Diabetic nephropathy(DN)is a microvascular complication of diabetes mellitus(DM).DN results from many factors,including changes in glomerular hemodynamics,oxidative stress and inflammation,and in-terstitial...Background:Diabetic nephropathy(DN)is a microvascular complication of diabetes mellitus(DM).DN results from many factors,including changes in glomerular hemodynamics,oxidative stress and inflammation,and in-terstitial fibrosis and tubular atrophy.Panax notoginseng,a commonly used Chinese medicine,has been used in the treatment of kidney disease.Notoginsenoside R1(NGR1),the main compound isolated from P.notoginseng,has been reported to have a renoprotective role in DN.However,the therapeutic effect and mechanism of NGR1 in DN remain unclear.Objective:The present study aimed to investigate the therapeutic effect and mechanism of NGR1 in DN.Methods:In this study,mouse podocytes(MPC-5 cells)and db/db mice were used to investigate the effect of NGR1 on DN in vitro and in vivo,respectively.Blood glucose,renal function,inflammatory factors,and PI3K/AKT-Nrf2-NLRP3 signaling pathway proteins were assessed.Results:The study results indicated that NGR1 reversed cell viability induced by high glucose(HG,30 mM).The related mechanism results showed that NGR1 decreased oxidative stress by inhibiting reactive oxygen species(ROS)level and upregulating the expression of Nrf2,NQO1,and HO-1 via TXNIP targeting.In addition,NLRP3 inflammasome and PI3K/AKT were engaged in NGR1-based protection against HG-stimulated podocytes.In db/db mice,NGR1 significantly decreased blood glucose,urine protein,urine output,blood urea nitrogen,and other parameters as well as reversed kidney injury by inhibiting oxidative stress and proinflammatory response.Conclusion:Taken together,this study revealed that NGR1 exerted a significant therapeutic effect on DN both in vitro and in vivo via a mechanism related to the TXNIP-Nrf2 pathway and NLRP3 inflammasome,suggesting that NGR1 is a potential therapeutic option for DN.展开更多
目的研究NgR1在CPR后大鼠脑组织中的表达。方法采用经皮电刺激致心脏骤停方法，60只SD大鼠分组，按照Uestein模式进行CPR，分别于ROSC（ restoration of spontaneous circulation）后1d、3d和7d处死动物，利用免疫荧光及Q-PCR方法分别...目的研究NgR1在CPR后大鼠脑组织中的表达。方法采用经皮电刺激致心脏骤停方法，60只SD大鼠分组，按照Uestein模式进行CPR，分别于ROSC（ restoration of spontaneous circulation）后1d、3d和7d处死动物，利用免疫荧光及Q-PCR方法分别检测脑组织中NgR1蛋白、NgR1mRNA的分布和变化。结果CPR后1d大鼠海马部位NgR1表达明显升高，CPR后7d降至正常。Q-PCR结果同免疫荧光细胞计数结果相似，但各时点NgR1 mRNA表达差异并无统计学意义（P〈0．05）。结论CPR后大鼠脑组织海马NgR1表达呈现一过性升高，为进一步探讨拮抗NgR1对大鼠CPR后脑功能障碍的作用，寻找改善脑复苏预后的新途径奠定基础。展开更多
基金supported by Guangxi Natural Science Foundation[2020GXNSFAA159070]China-ASEAN International Innovative Center for Health Industry of Traditional Chinese Medicine[AD20297142]Guangxi Collabrative Innovation Center for Scientific Achievements Transformation and Application on Traditional Chinese Medicine[05020058].
文摘Background:Diabetic nephropathy(DN)is a microvascular complication of diabetes mellitus(DM).DN results from many factors,including changes in glomerular hemodynamics,oxidative stress and inflammation,and in-terstitial fibrosis and tubular atrophy.Panax notoginseng,a commonly used Chinese medicine,has been used in the treatment of kidney disease.Notoginsenoside R1(NGR1),the main compound isolated from P.notoginseng,has been reported to have a renoprotective role in DN.However,the therapeutic effect and mechanism of NGR1 in DN remain unclear.Objective:The present study aimed to investigate the therapeutic effect and mechanism of NGR1 in DN.Methods:In this study,mouse podocytes(MPC-5 cells)and db/db mice were used to investigate the effect of NGR1 on DN in vitro and in vivo,respectively.Blood glucose,renal function,inflammatory factors,and PI3K/AKT-Nrf2-NLRP3 signaling pathway proteins were assessed.Results:The study results indicated that NGR1 reversed cell viability induced by high glucose(HG,30 mM).The related mechanism results showed that NGR1 decreased oxidative stress by inhibiting reactive oxygen species(ROS)level and upregulating the expression of Nrf2,NQO1,and HO-1 via TXNIP targeting.In addition,NLRP3 inflammasome and PI3K/AKT were engaged in NGR1-based protection against HG-stimulated podocytes.In db/db mice,NGR1 significantly decreased blood glucose,urine protein,urine output,blood urea nitrogen,and other parameters as well as reversed kidney injury by inhibiting oxidative stress and proinflammatory response.Conclusion:Taken together,this study revealed that NGR1 exerted a significant therapeutic effect on DN both in vitro and in vivo via a mechanism related to the TXNIP-Nrf2 pathway and NLRP3 inflammasome,suggesting that NGR1 is a potential therapeutic option for DN.
