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:To investigate the effect and possible mechanism of Qiliqiangxin capsule on myocardial fibrosis in rats with myocardial infarction(MI).Methods:The rat model of myocardial infarction was established by ligati...Objective:To investigate the effect and possible mechanism of Qiliqiangxin capsule on myocardial fibrosis in rats with myocardial infarction(MI).Methods:The rat model of myocardial infarction was established by ligation of anterior descending branch of left coronary artery.The rats were randomly divided into model group,Qiliqiangxin capsule group,captopril group after operation.Rats that without ligation were set as parallel control group,namely,the sham group.Cardiac pathology was observed by hematoxylin eosin(HE)staining after 4 weeks of treatment.Masson staining was used to observe myocardial fibrosis and calculate collagen volume fraction(CVF).The miR-133a and expression levels of transforming growth factor β1(TGF-β1),Smad 2,Smad 3,type Ⅰ collagen(col-Ⅰ),type Ⅲ collagen(col-Ⅲ)mRNA were examined by Real-time PCR.Results:Compared with the sham group,myocardial cells in model group were disordered,CVF was significantly increased(P<0.01),the expression levels of col-Ⅰ,col-ⅢmRNA were increased(P<0.01);besides,the expression level of miR-133a was significantly decreased(P<0.01),the expression levels of TGF-β1,Smad 2 and Smad 3 mRNA were increased(P<0.05,P<0.01).Compared with the model group,the arrangement of myocardial cells in Qiliqiangxin capsule group and captopril group were orderly and CVF was significantly decreased(P<0.05);the expression level of miR-133a was increased(P<0.05,P<0.01);the expression levels of TGF-β1,Smad 2 and Smad 3 mRNA were significantly decreased(P<0.01).Conclusion:Qiliqiangxin capsule can improve myocardial infarction rat myocardial tissue fibrosis,its mechanism may be in related with the regulation on miR-133a/TGF-β1/Smads signal pathway at the genetic level.展开更多
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National Natural Science Foundation of China(No.81973787)。
文摘Objective:To investigate the effect and possible mechanism of Qiliqiangxin capsule on myocardial fibrosis in rats with myocardial infarction(MI).Methods:The rat model of myocardial infarction was established by ligation of anterior descending branch of left coronary artery.The rats were randomly divided into model group,Qiliqiangxin capsule group,captopril group after operation.Rats that without ligation were set as parallel control group,namely,the sham group.Cardiac pathology was observed by hematoxylin eosin(HE)staining after 4 weeks of treatment.Masson staining was used to observe myocardial fibrosis and calculate collagen volume fraction(CVF).The miR-133a and expression levels of transforming growth factor β1(TGF-β1),Smad 2,Smad 3,type Ⅰ collagen(col-Ⅰ),type Ⅲ collagen(col-Ⅲ)mRNA were examined by Real-time PCR.Results:Compared with the sham group,myocardial cells in model group were disordered,CVF was significantly increased(P<0.01),the expression levels of col-Ⅰ,col-ⅢmRNA were increased(P<0.01);besides,the expression level of miR-133a was significantly decreased(P<0.01),the expression levels of TGF-β1,Smad 2 and Smad 3 mRNA were increased(P<0.05,P<0.01).Compared with the model group,the arrangement of myocardial cells in Qiliqiangxin capsule group and captopril group were orderly and CVF was significantly decreased(P<0.05);the expression level of miR-133a was increased(P<0.05,P<0.01);the expression levels of TGF-β1,Smad 2 and Smad 3 mRNA were significantly decreased(P<0.01).Conclusion:Qiliqiangxin capsule can improve myocardial infarction rat myocardial tissue fibrosis,its mechanism may be in related with the regulation on miR-133a/TGF-β1/Smads signal pathway at the genetic level.
