Spurred by the world information tide, China has organized a series of information projects, called the "Three Gold" projects. Recently I had an interview with Mr. Hu Qili, Minister of Electronics Industry, ...Spurred by the world information tide, China has organized a series of information projects, called the "Three Gold" projects. Recently I had an interview with Mr. Hu Qili, Minister of Electronics Industry, about the establishment of China’s modern Electronic Information Industry. Mr. Hu told me that information is the mark of development of a modern society and electronics is the major means of carrying information. Establishing展开更多
Objective:To investigate the pharmacological mechanism of Qili Qiangxin Capsule(QLQX)improvement of heart failure(HF)based on miR133a-endoplasmic reticulum stress(ERS)pathway.Methods:A left coronary artery ligation-in...Objective:To investigate the pharmacological mechanism of Qili Qiangxin Capsule(QLQX)improvement of heart failure(HF)based on miR133a-endoplasmic reticulum stress(ERS)pathway.Methods:A left coronary artery ligation-induced HF after myocardial infarction model was used in this study.Rats were randomly assigned to the sham group,the model group,the QLQX group[0.32 g/(kg·d)],and the captopril group[2.25 mg/(kg·d)],15 rats per group,followed by 4 weeks of medication.Cardiac function such as left ventricular ejection fraction(EF),fractional shortening(FS),left ventricular systolic pressure(LVSP),left ventricular end diastolic pressure(LVEDP),the maximal rate of increase of left ventricular pressure(+dp/dt max),and the maximal rate of decrease of left ventricular pressure(–dp/dt max)were monitored by echocardiography and hemodynamics.Hematoxylin and eosin(HE)and Masson stainings were used to visualize pathological changes in myocardial tissue.The m RNA expression of mi R133a,glucose-regulated protein78(GRP78),inositol-requiring enzyme 1(IRE1),activating transcription factor 6(ATF6),X-box binding protein1(XBP1),C/EBP homologous protein(CHOP)and Caspase 12 were detected by RT-PCR.The protein expression of GRP78,p-IRE1/IRE1ratio,cleaved-ATF6,XBP1-s(the spliced form of XBP1),CHOP and Caspase 12 were detected by Western blot.Td T-mediated d UTP nick-end labeling(TUNEL)staining was used to detect the rate of apoptosis.Results:QLQX significantly improved cardiac function as evidenced by increased EF,FS,LVSP,+dp/dt max,-dp/dt max,and decreased LVEDP(P<0.05,P<0.01).HE staining showed that QLQX ameliorated cardiac pathologic damage to some extent.Masson staining indicated that QLQX significantly reduced collagen volume fraction in myocardial tissue(P<0.01).Results from RT-PCR and Western blot showed that QLQX significantly increased the expression of mi R133a and inhibited the m RNA expressions of GRP78,IRE1,ATF6 and XBP1,as well as decreased the protein expressions of GRP78,cleaved-ATF6 and XBP1-s and decreased p-IRE1/IRE1 ratio(P<0.05,P<0.01).Further studies showed that QLQX significantly reduced the expression of CHOP and Caspase12,resulting in a significant reduction in apoptosis rate(P<0.05,P<0.01).Conclusion:The pharmacological mechanism of QLQX in improving HF is partly attributed to its regulatory effect on the mi R133a-IRE1/XBP1 pathway.展开更多
Objective: Qili Qiangxin(QLQX), a compound herbal medicine formula, is used effectively to treat congestive heart failure in China. However, the molecular mechanisms of the cardioprotective effect are still unclear. T...Objective: Qili Qiangxin(QLQX), a compound herbal medicine formula, is used effectively to treat congestive heart failure in China. However, the molecular mechanisms of the cardioprotective effect are still unclear. This study explores the cardioprotective effect and mechanism of QLQX using the hypoxiareoxygenation(H/R)-induced myocardial injury model.Methods: The main chemical constituents of QLQX were analyzed using high-performance liquid chromatography-evaporative light-scattering detection. The model of H/R-induced myocardial injury in H9c2 cells was developed to simulate myocardial ischemia–reperfusion injury. Apoptosis, autophagy,and generation of reactive oxygen species(ROS) were measured to assess the protective effect of QLQX. Proteins related to autophagy, apoptosis and signalling pathways were detected using Western blotting.Results: Apoptosis, autophagy and the excessive production of ROS induced by H/R were significantly reduced after treating the H9c2 cells with QLQX. QLQX treatment at concentrations of 50 and 250 μg/mL caused significant reduction in the levels of LC3Ⅱ and p62 degradation(P < 0.05), and also suppressed the AMPK/mTOR signalling pathway. Furthermore, the AMPK inhibitor Compound C(at 0.5 μmol/L),and QLQX(250 μg/mL) significantly inhibited H/R-induced autophagy and apoptosis(P < 0.01), while AICAR(an AMPK activator, at 0.5 mmol/L) increased cardiomyocyte apoptosis and autophagy and abolished the anti-apoptotic effect of QLQX. Similar phenomena were also observed on the expressions of apoptotic and autophagic proteins, demonstrating that QLQX reduced the apoptosis and autophagy in the H/R-induced injury model via inhibiting the AMPK/mTOR pathway. Moreover, ROS scavenger,N-Acetyl-L-cysteine(NAC, at 2.5 mmol/L), significantly reduced H/R-triggered cell apoptosis and autophagy(P < 0.01). Meanwhile, NAC treatment down-regulated the ratio of phosphorylation of AMPK/AMPK(P < 0.01), which showed a similar effect to QLQX.Conclusion: QLQX plays a cardioprotective role by alleviating apoptotic and autophagic cell death through inhibition of the ROS/AMPK/mTOR signalling pathway.展开更多
文摘Spurred by the world information tide, China has organized a series of information projects, called the "Three Gold" projects. Recently I had an interview with Mr. Hu Qili, Minister of Electronics Industry, about the establishment of China’s modern Electronic Information Industry. Mr. Hu told me that information is the mark of development of a modern society and electronics is the major means of carrying information. Establishing
基金Supported by 2022 Science and Technology Innovation Project of Dongzhimen Hospital,Beijing University of Chinese Medicine (No.DZMKJCX-2022-008)。
文摘Objective:To investigate the pharmacological mechanism of Qili Qiangxin Capsule(QLQX)improvement of heart failure(HF)based on miR133a-endoplasmic reticulum stress(ERS)pathway.Methods:A left coronary artery ligation-induced HF after myocardial infarction model was used in this study.Rats were randomly assigned to the sham group,the model group,the QLQX group[0.32 g/(kg·d)],and the captopril group[2.25 mg/(kg·d)],15 rats per group,followed by 4 weeks of medication.Cardiac function such as left ventricular ejection fraction(EF),fractional shortening(FS),left ventricular systolic pressure(LVSP),left ventricular end diastolic pressure(LVEDP),the maximal rate of increase of left ventricular pressure(+dp/dt max),and the maximal rate of decrease of left ventricular pressure(–dp/dt max)were monitored by echocardiography and hemodynamics.Hematoxylin and eosin(HE)and Masson stainings were used to visualize pathological changes in myocardial tissue.The m RNA expression of mi R133a,glucose-regulated protein78(GRP78),inositol-requiring enzyme 1(IRE1),activating transcription factor 6(ATF6),X-box binding protein1(XBP1),C/EBP homologous protein(CHOP)and Caspase 12 were detected by RT-PCR.The protein expression of GRP78,p-IRE1/IRE1ratio,cleaved-ATF6,XBP1-s(the spliced form of XBP1),CHOP and Caspase 12 were detected by Western blot.Td T-mediated d UTP nick-end labeling(TUNEL)staining was used to detect the rate of apoptosis.Results:QLQX significantly improved cardiac function as evidenced by increased EF,FS,LVSP,+dp/dt max,-dp/dt max,and decreased LVEDP(P<0.05,P<0.01).HE staining showed that QLQX ameliorated cardiac pathologic damage to some extent.Masson staining indicated that QLQX significantly reduced collagen volume fraction in myocardial tissue(P<0.01).Results from RT-PCR and Western blot showed that QLQX significantly increased the expression of mi R133a and inhibited the m RNA expressions of GRP78,IRE1,ATF6 and XBP1,as well as decreased the protein expressions of GRP78,cleaved-ATF6 and XBP1-s and decreased p-IRE1/IRE1 ratio(P<0.05,P<0.01).Further studies showed that QLQX significantly reduced the expression of CHOP and Caspase12,resulting in a significant reduction in apoptosis rate(P<0.05,P<0.01).Conclusion:The pharmacological mechanism of QLQX in improving HF is partly attributed to its regulatory effect on the mi R133a-IRE1/XBP1 pathway.
基金supported by Guangdong Basic and Applied Basic Research Foundation (No. 2021A1515110055)。
文摘Objective: Qili Qiangxin(QLQX), a compound herbal medicine formula, is used effectively to treat congestive heart failure in China. However, the molecular mechanisms of the cardioprotective effect are still unclear. This study explores the cardioprotective effect and mechanism of QLQX using the hypoxiareoxygenation(H/R)-induced myocardial injury model.Methods: The main chemical constituents of QLQX were analyzed using high-performance liquid chromatography-evaporative light-scattering detection. The model of H/R-induced myocardial injury in H9c2 cells was developed to simulate myocardial ischemia–reperfusion injury. Apoptosis, autophagy,and generation of reactive oxygen species(ROS) were measured to assess the protective effect of QLQX. Proteins related to autophagy, apoptosis and signalling pathways were detected using Western blotting.Results: Apoptosis, autophagy and the excessive production of ROS induced by H/R were significantly reduced after treating the H9c2 cells with QLQX. QLQX treatment at concentrations of 50 and 250 μg/mL caused significant reduction in the levels of LC3Ⅱ and p62 degradation(P < 0.05), and also suppressed the AMPK/mTOR signalling pathway. Furthermore, the AMPK inhibitor Compound C(at 0.5 μmol/L),and QLQX(250 μg/mL) significantly inhibited H/R-induced autophagy and apoptosis(P < 0.01), while AICAR(an AMPK activator, at 0.5 mmol/L) increased cardiomyocyte apoptosis and autophagy and abolished the anti-apoptotic effect of QLQX. Similar phenomena were also observed on the expressions of apoptotic and autophagic proteins, demonstrating that QLQX reduced the apoptosis and autophagy in the H/R-induced injury model via inhibiting the AMPK/mTOR pathway. Moreover, ROS scavenger,N-Acetyl-L-cysteine(NAC, at 2.5 mmol/L), significantly reduced H/R-triggered cell apoptosis and autophagy(P < 0.01). Meanwhile, NAC treatment down-regulated the ratio of phosphorylation of AMPK/AMPK(P < 0.01), which showed a similar effect to QLQX.Conclusion: QLQX plays a cardioprotective role by alleviating apoptotic and autophagic cell death through inhibition of the ROS/AMPK/mTOR signalling pathway.
