OBJECTIVE Regulating P2x7R-NLRP3 inflammasome activation might be a potential therapeutic strategy to treat alcoholic hepatosteatosis.We investigated whether this process would be modulated by gentiopicroside(GPS),whi...OBJECTIVE Regulating P2x7R-NLRP3 inflammasome activation might be a potential therapeutic strategy to treat alcoholic hepatosteatosis.We investigated whether this process would be modulated by gentiopicroside(GPS),which is attributed to the bitterness of gentian root extract.METHODS An in vivo model was established by intragastrically treating mice with ethanol,and an in vitro model was created by treating HepG2 cells with ethanol or treating RAW 264.7 macrophages and murine bone marrow-derived macrophages(BMDMs) with lipopolysaccharides(LPS) plus adenosine triphos.phate(ATP).RESULTS In alcoholic hepatosteatotic mice model,GPS decreased serum aminotrans.ferase and triglyceride accumulation.GPS regulated sterol regulatory element-binding protein-1(Srebp1),peroxisome proliferators-actived receptors α(PPARα) and acetyl CoA carboxylase(ACC) expression via elevating liver kinase B1(LKB1)/AMP-activated Kinase(AMPK).Suppression of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),caspase-1 and expression by GPS resulted in the inhibition of interleukin-1β(IL-1β) production.In ethanol-exposed HepG2 cells,GPS reduced lipo.genesis and promoted lipid oxidation via P2x7R-NLRP3 inflammasome activation.P2x7R silencing enhanced AMPK activity,and reduced Srebp1 expression in ethanol-treated hepatocytes.GPS down.regulated P2x7R-mediated inflammatory response to extracellular ATP in LPS-primed RAW 264.7 macro.phages and BMDMs.Additionally,P2x7R deficiency attenuated IL-1β cleavage in RAW 264.7 macro.phages,and GPS further suppressed IL-1β cleavage.CONCLUSION Activation of LKB1/AMPK signaling by GPS might be mediated by P2x7R-NLRP3 inflammasome,suggesting a therapeutic utility of P2x7R blockade in alcoholic hepatosteatosis treatment.展开更多
OBJECTIVE Dihydroquercetin(TAX) is the most abundant dihydroflavone found in on.ions,milk thistle and Douglas fir bark.We investigated whether TAX could inhibit the lipid accumulation in alcoholic liver steatosis in v...OBJECTIVE Dihydroquercetin(TAX) is the most abundant dihydroflavone found in on.ions,milk thistle and Douglas fir bark.We investigated whether TAX could inhibit the lipid accumulation in alcoholic liver steatosis in vivo and in vitro.METHODS An in vivo model was established by intragas.trically treating mice with ethanol,and an in vitro model was created by treating HepG2 cells with etha.nol.RESULTS TAX regulated Sterol Regulatory Element-binding Protein-1(SREBP1) and Acetyl CoA Carboxylase(ACC) expression via elevating Liver Kinase B1(LKB1)/AMP-activated Kinase(AMPK)phosphorylation.Also,TAX upregulated SIRT1 expression,which suppressed by ethanal intake.Suppression of Purinergic 2X7 receptor(P2x7R),nucleotide-binding oligomerization domain-like re.ceptor protein 3(NLRP3) and Cysteine protease-1(caspase-1) cleavage by TAX resulted in the inhibi.tion of Interleukin-1β(IL-1β) production and release.Additionally,TAX reduced lipogenesis and pro.moted lipid oxidation via the regulation of AMPK and ACC in ethanol-treated steatotic HepG2 cell.TAX downregulated IL-1β cleavage response to Lipopolysaccharides(LPS) plus adenosine triphosphate(ATP) stimulation in HepG2 cells.P2x7R deficiency attenuated lipid accumulation with increasing AMPK activity and decreasing SREBP1 expression in ethanol-treated HepG2 cells.CONCLUSION Our data showed that TAX exhibited the inhibitory properties on lipogenesis and hepatoprotective ca.pacity,indicating that TAX has therapeutic potential for preventing alcoholic liver steatosis.展开更多
目的:探讨萆苓祛痛方对2型糖尿病(T2DM)合并痛风性关节炎(GA)患者血清NLRP3、P2X7R、FN及肝脂肪变性的影响。方法:选取2019年1月至2022年12月在安徽中医药大学第一附属医院就诊的T2DM合并GA患者64例,随机分为萆苓祛痛方组(中药组,32例)...目的:探讨萆苓祛痛方对2型糖尿病(T2DM)合并痛风性关节炎(GA)患者血清NLRP3、P2X7R、FN及肝脂肪变性的影响。方法:选取2019年1月至2022年12月在安徽中医药大学第一附属医院就诊的T2DM合并GA患者64例,随机分为萆苓祛痛方组(中药组,32例)和布洛芬组(西药组,32例),同期健康体检30例作为对照组。两组维持基础治疗,西药组加布洛芬,中药组加萆苓祛痛方治疗。连续治疗8周后评估患者治疗前后中医证候评分,比较治疗前后空腹血糖(FPG)、餐后2 h血糖(2 h PG)、糖化血红蛋白A1c(HbA1c)、空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)、血尿酸(SUA)、血肌酐(SCr)、总胆固醇(TC)、甘油三酯(TG)、高密低脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆度醇(LDL-C)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、受控衰减参数(CAP)、肝脏硬度(LSM)、NOD样受体热蛋白结构域相关蛋白3(NLRP3)、嘌呤能离子通道型受体7(P2X7R)、血清纤维连接蛋白(FN)的差异,记录用药期间出现的药物不良反应。结果:与本组治疗前比较,中药组西药组患者关节红肿疼痛、关节灼热、尿色黄、舌红苔黄腻及中医证候总积分均明显降低(P<0.05,P<0.01),中药组患者口干口渴、多饮多尿、脉滑数积分显著降低(P<0.01);与西药组治疗后比较,中药组各证候积分及总积分下降更显著(P<0.05,P<0.01)。与本组治疗前比较,中药组西药组治疗后FPG、2 h PG、HbA1c、SCr、SUA、TG、TC、LDL-C水平下降(P<0.05,P<0.01),中药组患者HOMA-IR、ALT、AST、HDL-C水平下降(P<0.05,P<0.01);与西药组治疗后比较,中药组患者除HDL-C外各实验室检查指标均明显降低(P<0.05,P<0.01)。治疗前,中药组西药组NLRP3、P2X7R、FN水平均高于对照组(P<0.01);与本组治疗前比较,两组患者治疗后NLRP3、P2X7R水平均显著降低(P<0.01);中药组FN水平明显下降(P<0.01);与西药组治疗后比较,中药组NLRP3、P2X7R、FN水平明显降低(P<0.01)。治疗前,中药组西药组CAP、LSM水平均高于对照组(P<0.01);与本组治疗前比较,中药组西药组治疗后CAP、LSM水平降低(P<0.05,P<0.01);与西药组治疗后比较,中药组下降更为显著(P<0.01)。不良反应发生率比较,中药组为3.13%(1/32),西药组为15.63%(5/32),差异无统计学意义。结论:萆苓祛痛方对2型糖尿病合并痛风性关节炎患者的疗效更佳,能显著减轻患者关节红肿热痛、活动受限、口干多饮等症状,降低血糖、血尿酸、血脂,抑制NLRP3、P2X7R、FN的高表达,改善肝脂肪变性。展开更多
基金supported by National Natural Science Foundation of China(8156059781260664+1 种基金8136065881660689)
文摘OBJECTIVE Regulating P2x7R-NLRP3 inflammasome activation might be a potential therapeutic strategy to treat alcoholic hepatosteatosis.We investigated whether this process would be modulated by gentiopicroside(GPS),which is attributed to the bitterness of gentian root extract.METHODS An in vivo model was established by intragastrically treating mice with ethanol,and an in vitro model was created by treating HepG2 cells with ethanol or treating RAW 264.7 macrophages and murine bone marrow-derived macrophages(BMDMs) with lipopolysaccharides(LPS) plus adenosine triphos.phate(ATP).RESULTS In alcoholic hepatosteatotic mice model,GPS decreased serum aminotrans.ferase and triglyceride accumulation.GPS regulated sterol regulatory element-binding protein-1(Srebp1),peroxisome proliferators-actived receptors α(PPARα) and acetyl CoA carboxylase(ACC) expression via elevating liver kinase B1(LKB1)/AMP-activated Kinase(AMPK).Suppression of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),caspase-1 and expression by GPS resulted in the inhibition of interleukin-1β(IL-1β) production.In ethanol-exposed HepG2 cells,GPS reduced lipo.genesis and promoted lipid oxidation via P2x7R-NLRP3 inflammasome activation.P2x7R silencing enhanced AMPK activity,and reduced Srebp1 expression in ethanol-treated hepatocytes.GPS down.regulated P2x7R-mediated inflammatory response to extracellular ATP in LPS-primed RAW 264.7 macro.phages and BMDMs.Additionally,P2x7R deficiency attenuated IL-1β cleavage in RAW 264.7 macro.phages,and GPS further suppressed IL-1β cleavage.CONCLUSION Activation of LKB1/AMPK signaling by GPS might be mediated by P2x7R-NLRP3 inflammasome,suggesting a therapeutic utility of P2x7R blockade in alcoholic hepatosteatosis treatment.
基金supported by National Natural Science Foundation of China(8156059781260664+1 种基金81360658and 81660689)
文摘OBJECTIVE Dihydroquercetin(TAX) is the most abundant dihydroflavone found in on.ions,milk thistle and Douglas fir bark.We investigated whether TAX could inhibit the lipid accumulation in alcoholic liver steatosis in vivo and in vitro.METHODS An in vivo model was established by intragas.trically treating mice with ethanol,and an in vitro model was created by treating HepG2 cells with etha.nol.RESULTS TAX regulated Sterol Regulatory Element-binding Protein-1(SREBP1) and Acetyl CoA Carboxylase(ACC) expression via elevating Liver Kinase B1(LKB1)/AMP-activated Kinase(AMPK)phosphorylation.Also,TAX upregulated SIRT1 expression,which suppressed by ethanal intake.Suppression of Purinergic 2X7 receptor(P2x7R),nucleotide-binding oligomerization domain-like re.ceptor protein 3(NLRP3) and Cysteine protease-1(caspase-1) cleavage by TAX resulted in the inhibi.tion of Interleukin-1β(IL-1β) production and release.Additionally,TAX reduced lipogenesis and pro.moted lipid oxidation via the regulation of AMPK and ACC in ethanol-treated steatotic HepG2 cell.TAX downregulated IL-1β cleavage response to Lipopolysaccharides(LPS) plus adenosine triphosphate(ATP) stimulation in HepG2 cells.P2x7R deficiency attenuated lipid accumulation with increasing AMPK activity and decreasing SREBP1 expression in ethanol-treated HepG2 cells.CONCLUSION Our data showed that TAX exhibited the inhibitory properties on lipogenesis and hepatoprotective ca.pacity,indicating that TAX has therapeutic potential for preventing alcoholic liver steatosis.
文摘目的:探讨萆苓祛痛方对2型糖尿病(T2DM)合并痛风性关节炎(GA)患者血清NLRP3、P2X7R、FN及肝脂肪变性的影响。方法:选取2019年1月至2022年12月在安徽中医药大学第一附属医院就诊的T2DM合并GA患者64例,随机分为萆苓祛痛方组(中药组,32例)和布洛芬组(西药组,32例),同期健康体检30例作为对照组。两组维持基础治疗,西药组加布洛芬,中药组加萆苓祛痛方治疗。连续治疗8周后评估患者治疗前后中医证候评分,比较治疗前后空腹血糖(FPG)、餐后2 h血糖(2 h PG)、糖化血红蛋白A1c(HbA1c)、空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)、血尿酸(SUA)、血肌酐(SCr)、总胆固醇(TC)、甘油三酯(TG)、高密低脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆度醇(LDL-C)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、受控衰减参数(CAP)、肝脏硬度(LSM)、NOD样受体热蛋白结构域相关蛋白3(NLRP3)、嘌呤能离子通道型受体7(P2X7R)、血清纤维连接蛋白(FN)的差异,记录用药期间出现的药物不良反应。结果:与本组治疗前比较,中药组西药组患者关节红肿疼痛、关节灼热、尿色黄、舌红苔黄腻及中医证候总积分均明显降低(P<0.05,P<0.01),中药组患者口干口渴、多饮多尿、脉滑数积分显著降低(P<0.01);与西药组治疗后比较,中药组各证候积分及总积分下降更显著(P<0.05,P<0.01)。与本组治疗前比较,中药组西药组治疗后FPG、2 h PG、HbA1c、SCr、SUA、TG、TC、LDL-C水平下降(P<0.05,P<0.01),中药组患者HOMA-IR、ALT、AST、HDL-C水平下降(P<0.05,P<0.01);与西药组治疗后比较,中药组患者除HDL-C外各实验室检查指标均明显降低(P<0.05,P<0.01)。治疗前,中药组西药组NLRP3、P2X7R、FN水平均高于对照组(P<0.01);与本组治疗前比较,两组患者治疗后NLRP3、P2X7R水平均显著降低(P<0.01);中药组FN水平明显下降(P<0.01);与西药组治疗后比较,中药组NLRP3、P2X7R、FN水平明显降低(P<0.01)。治疗前,中药组西药组CAP、LSM水平均高于对照组(P<0.01);与本组治疗前比较,中药组西药组治疗后CAP、LSM水平降低(P<0.05,P<0.01);与西药组治疗后比较,中药组下降更为显著(P<0.01)。不良反应发生率比较,中药组为3.13%(1/32),西药组为15.63%(5/32),差异无统计学意义。结论:萆苓祛痛方对2型糖尿病合并痛风性关节炎患者的疗效更佳,能显著减轻患者关节红肿热痛、活动受限、口干多饮等症状,降低血糖、血尿酸、血脂,抑制NLRP3、P2X7R、FN的高表达,改善肝脂肪变性。
