The activation of the sirtuin1(SIRT1)/nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase 1(HO-1)pathway has been shown to mitigate oxidative stress-induced apoptosis and mitochondrial damage by reducing ...The activation of the sirtuin1(SIRT1)/nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase 1(HO-1)pathway has been shown to mitigate oxidative stress-induced apoptosis and mitochondrial damage by reducing reactive oxygen species(ROS)levels.Clinical trials have demonstrated that Zhongfeng Xingnao Liquid(ZFXN)ameliorates post-stroke cognitive impairment(PSCI).However,the underlying mechanism,particularly whether it involves protecting mitochondria and inhibiting apoptosis through the SIRT1/Nrf2/HO-1 pathway,remains unclear.This study employed an oxygen-glucose deprivation(OGD)cell model using SHSY5Y cells and induced PSCI in rats through modified bilateral carotid artery ligation(2VO).The effects of ZFXN on learning and memory,neuroprotective activity,mitochondrial function,oxidative stress,and the SIRT1/Nrf2/HO-1 pathway were evaluated both in vivo and in vitro.Results indicated that ZFXN significantly increased the B-cell lymphoma 2(Bcl2)/Bcl2-associated X(Bax)ratio,reduced terminal deoxynucleotidyl transferase-mediated d UTP nickend-labeling(TUNEL)+cells,and markedly improved cognition,synaptic plasticity,and neuronal function in the hippocampus and cortex.Furthermore,ZFXN exhibited potent antioxidant activity,evidenced by decreased ROS and malondialdehyde(MDA)content and increased superoxide dismutase(SOD),catalase(CAT),and glutathione(GSH)levels.ZFXN also demonstrated considerable enhancement of mitochondrial membrane potential(MMP),Tom 20 fluorescence intensity,adenosine triphosphate(ATP)and energy charge(EC)levels,and mitochondrial complexⅠandⅢactivity,thereby inhibiting mitochondrial damage.Additionally,ZFXN significantly increased SIRT1 activity and elevated SIRT1,nuclear Nrf2,and HO-1 levels.Notably,these effects were substantially counteracted when SIRT1 was suppressed by the inhibitor EX-527 in vitro.In conclusion,ZFXN alleviates PSCI by activating the SIRT1/Nrf2/HO-1 pathway and preventing mitochondrial damage.展开更多
目的观察西格列汀治疗肥胖2型糖尿病(T2DM)的临床疗效及安全性。方法选择2022年1月至2024年2月南阳市第一人民医院接诊的肥胖T2DM患者106例为研究对象。按治疗方法将患者分为对照组(n=53)和观察组(n=53)。2组患者均给予饮食控制及运动...目的观察西格列汀治疗肥胖2型糖尿病(T2DM)的临床疗效及安全性。方法选择2022年1月至2024年2月南阳市第一人民医院接诊的肥胖T2DM患者106例为研究对象。按治疗方法将患者分为对照组(n=53)和观察组(n=53)。2组患者均给予饮食控制及运动干预、调脂治疗、营养辅导等基础治疗,在此基础上,对照组患者给予盐酸二甲双胍片,观察组患者给予盐酸二甲双胍片和磷酸西格列汀片,连续治疗4个月。比较2组患者的治疗效果。分别于治疗前后,记录2组患者的体质量指数(BMI);采用糖化血红蛋白仪检测糖化血红蛋白(HbA1c)水平;全自动生化分析仪检测空腹血糖(FBG)、餐后2 h血糖(2 h PG)、空腹胰岛素(Fins)和三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)水平,计算稳态模型评估的胰岛素抵抗指数(HOMA-IR);采用双抗体夹心酶联免疫吸附试验检测血清核因子E2相关因子2(Nrf2)、缺氧诱导因子-α(HIF-α)、C反应蛋白(CRP)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平。记录2组患者用药期间恶心呕吐、腹泻、外阴瘙痒、低血糖等不良反应发生情况。采用国家胆固醇教育计划-成人治疗小组第三组推荐的评分工具Framingham 10年冠心病危险评分(FRS)来评估心血管疾病发生风险。结果对照组和观察组患者的治疗总有效率分别为77.36%(41/53)、92.45%(49/53),观察组患者的治疗总有效率显著高于对照组(χ^(2)=4.711,P<0.05)。治疗前,2组患者的BMI及HbA1c、FBG、2 h PG、Fins、TG、TC、LDL-C、HOMA-IR等糖脂代谢指标比较差异无统计学意义(P>0.05)。2组患者治疗后BMI、FBG、2 h PG、HbA1c、HOMA-IR、TG、TC、LDL-C水平均显著低于治疗前,Fins、HDL-C水平显著高于治疗前(P<0.05)。治疗后,观察组患者的BMI、FBG、2 h PG、HbA1c、HOMA-IR、TG、TC、LDL-C水平均显著低于对照组,Fins、HDL-C水平显著高于对照组(P<0.05)。治疗前,2组患者血清Nrf2、HIF-α水平比较差异无统计学意义(P>0.05)。2组患者治疗后血清Nrf2、HIF-α水平显著低于治疗前(P<0.05)。治疗后,观察组患者血清Nrf2、HIF-α水平显著低于对照组(P<0.05)。治疗前,2组患者的血清CRP、IL-6、TNF-α水平比较差异无统计学意义(P>0.05)。2组患者治疗后血清CRP、IL-6、TNF-α水平显著低于治疗前(P<0.05)。治疗后,观察组患者血清CRP、IL-6、TNF-α水平显著低于对照组(P<0.05)。对照组和观察组患者不良反应发生率分别为5.66%(3/53)、9.43%(5/53),2组患者不良反应发生率比较差异无统计学意义(χ^(2)=0.135,P>0.05)。观察组患者治疗结束后3个月的FRS评分显著低于对照组(t=7.572,P<0.05)。观察组4例(7.55%)患者发生心血管疾病的风险为中高危,49例为低危;对照组12例(22.64%)患者发生心血管疾病的风险为中高危,41例为低危。观察组发生心血管疾病风险中高危患者占比显著低于对照组(χ^(2)=4.711,P<0.05)。结论西格列汀治疗肥胖T2DM疗效较好,可显著改善患者的糖脂代谢,下调血清Nrf2、HIF-α表达水平及炎症因子水平,减少心血管疾病风险,且安全性好。展开更多
基金supported by the Science&Technology Department of Sichuan Province(No.2019YFS0040)the Improvement Plan of“Xinglin Scholar”Scientific Research Talent,Chengdu University of Traditional Chinese Medicine(No.XKTD2022002)。
文摘The activation of the sirtuin1(SIRT1)/nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase 1(HO-1)pathway has been shown to mitigate oxidative stress-induced apoptosis and mitochondrial damage by reducing reactive oxygen species(ROS)levels.Clinical trials have demonstrated that Zhongfeng Xingnao Liquid(ZFXN)ameliorates post-stroke cognitive impairment(PSCI).However,the underlying mechanism,particularly whether it involves protecting mitochondria and inhibiting apoptosis through the SIRT1/Nrf2/HO-1 pathway,remains unclear.This study employed an oxygen-glucose deprivation(OGD)cell model using SHSY5Y cells and induced PSCI in rats through modified bilateral carotid artery ligation(2VO).The effects of ZFXN on learning and memory,neuroprotective activity,mitochondrial function,oxidative stress,and the SIRT1/Nrf2/HO-1 pathway were evaluated both in vivo and in vitro.Results indicated that ZFXN significantly increased the B-cell lymphoma 2(Bcl2)/Bcl2-associated X(Bax)ratio,reduced terminal deoxynucleotidyl transferase-mediated d UTP nickend-labeling(TUNEL)+cells,and markedly improved cognition,synaptic plasticity,and neuronal function in the hippocampus and cortex.Furthermore,ZFXN exhibited potent antioxidant activity,evidenced by decreased ROS and malondialdehyde(MDA)content and increased superoxide dismutase(SOD),catalase(CAT),and glutathione(GSH)levels.ZFXN also demonstrated considerable enhancement of mitochondrial membrane potential(MMP),Tom 20 fluorescence intensity,adenosine triphosphate(ATP)and energy charge(EC)levels,and mitochondrial complexⅠandⅢactivity,thereby inhibiting mitochondrial damage.Additionally,ZFXN significantly increased SIRT1 activity and elevated SIRT1,nuclear Nrf2,and HO-1 levels.Notably,these effects were substantially counteracted when SIRT1 was suppressed by the inhibitor EX-527 in vitro.In conclusion,ZFXN alleviates PSCI by activating the SIRT1/Nrf2/HO-1 pathway and preventing mitochondrial damage.
文摘目的观察西格列汀治疗肥胖2型糖尿病(T2DM)的临床疗效及安全性。方法选择2022年1月至2024年2月南阳市第一人民医院接诊的肥胖T2DM患者106例为研究对象。按治疗方法将患者分为对照组(n=53)和观察组(n=53)。2组患者均给予饮食控制及运动干预、调脂治疗、营养辅导等基础治疗,在此基础上,对照组患者给予盐酸二甲双胍片,观察组患者给予盐酸二甲双胍片和磷酸西格列汀片,连续治疗4个月。比较2组患者的治疗效果。分别于治疗前后,记录2组患者的体质量指数(BMI);采用糖化血红蛋白仪检测糖化血红蛋白(HbA1c)水平;全自动生化分析仪检测空腹血糖(FBG)、餐后2 h血糖(2 h PG)、空腹胰岛素(Fins)和三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)水平,计算稳态模型评估的胰岛素抵抗指数(HOMA-IR);采用双抗体夹心酶联免疫吸附试验检测血清核因子E2相关因子2(Nrf2)、缺氧诱导因子-α(HIF-α)、C反应蛋白(CRP)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平。记录2组患者用药期间恶心呕吐、腹泻、外阴瘙痒、低血糖等不良反应发生情况。采用国家胆固醇教育计划-成人治疗小组第三组推荐的评分工具Framingham 10年冠心病危险评分(FRS)来评估心血管疾病发生风险。结果对照组和观察组患者的治疗总有效率分别为77.36%(41/53)、92.45%(49/53),观察组患者的治疗总有效率显著高于对照组(χ^(2)=4.711,P<0.05)。治疗前,2组患者的BMI及HbA1c、FBG、2 h PG、Fins、TG、TC、LDL-C、HOMA-IR等糖脂代谢指标比较差异无统计学意义(P>0.05)。2组患者治疗后BMI、FBG、2 h PG、HbA1c、HOMA-IR、TG、TC、LDL-C水平均显著低于治疗前,Fins、HDL-C水平显著高于治疗前(P<0.05)。治疗后,观察组患者的BMI、FBG、2 h PG、HbA1c、HOMA-IR、TG、TC、LDL-C水平均显著低于对照组,Fins、HDL-C水平显著高于对照组(P<0.05)。治疗前,2组患者血清Nrf2、HIF-α水平比较差异无统计学意义(P>0.05)。2组患者治疗后血清Nrf2、HIF-α水平显著低于治疗前(P<0.05)。治疗后,观察组患者血清Nrf2、HIF-α水平显著低于对照组(P<0.05)。治疗前,2组患者的血清CRP、IL-6、TNF-α水平比较差异无统计学意义(P>0.05)。2组患者治疗后血清CRP、IL-6、TNF-α水平显著低于治疗前(P<0.05)。治疗后,观察组患者血清CRP、IL-6、TNF-α水平显著低于对照组(P<0.05)。对照组和观察组患者不良反应发生率分别为5.66%(3/53)、9.43%(5/53),2组患者不良反应发生率比较差异无统计学意义(χ^(2)=0.135,P>0.05)。观察组患者治疗结束后3个月的FRS评分显著低于对照组(t=7.572,P<0.05)。观察组4例(7.55%)患者发生心血管疾病的风险为中高危,49例为低危;对照组12例(22.64%)患者发生心血管疾病的风险为中高危,41例为低危。观察组发生心血管疾病风险中高危患者占比显著低于对照组(χ^(2)=4.711,P<0.05)。结论西格列汀治疗肥胖T2DM疗效较好,可显著改善患者的糖脂代谢,下调血清Nrf2、HIF-α表达水平及炎症因子水平,减少心血管疾病风险,且安全性好。
