This study aimed to investigate the effects of Zhiwei Fuwei Pills on mitochondrial apoptosis in the rat model of precancerous lesions of gastric cancer(PLGC) based on the microRNA-21(miRNA-21)/B-cell lymphoma-2(Bcl-2) signaling pathway. Eighty-five 5-week-old male SPF-grade SD rats were selected, of which 75 were fed with N-methyl-N'-nitro-N-nitrosoguanidine(MNNG) for multifactorial modeling, and the PLGC model was established after 26 weeks. The rats were randomly grouped as follows: model, folic acid(0.002 g·kg~(-1)), low-dose(0.42 g·kg~(-1)) Zhiwei Fuwei Pills, medium-dose(0.84 g·kg~(-1)) Zhiwei Fuwei Pills, and high-dose(1.67 g·kg~(-1)) Zhiwei Fuwei Pills, with 15 rats in each group. Additionally, 10 rats were assigned to a blank group and administrated with an equivalent volume of normal saline by gavage. After four weeks of continuous drug administration, the gastric mucosal tissue was collected. Hematoxylin-eosin(HE) staining was performed to reveal the pathological changes in the gastric mucosa. Terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL) was employed to detect apoptosis in gastric mucosal epithelial cells. RT-PCR was adopted to determine the mRNA levels of miRNA-21, phosphatase and tensin homolog(PTEN), Bcl-2, Bcl-2-associated X protein(Bax), and cysteinyl aspartate-specific protease 3(caspase-3). Western blot was employed to determine the protein levels of PTEN, Bcl-2, Bax, and caspase-3. Immunohistochemistry(IHC) was used to detect the positive expression of PTEN, Bcl-2, and Bax in the gastric mucosal tissue. Transmission electron microscopy(TEM) was employed to observe the morphological and structural changes in mitochondria. The results showed that compared with model group, the drug administration groups showed alleviated pathological changes, with increased apoptotic cells, down-regulated mRNA levels of miRNA-21 and Bcl-2, up-regulated mRNA and protein levels of PTEN, Bax, and caspase-3, and down-regulated protein level of Bcl-2. In addition, the drug administration groups exhibited mitochondrial swelling and rupture and reduction of cristae, which indicated mitochondrial apoptosis. These findings suggest that Zhiwei Fuwei Pills can effectively improve mitochondrial apoptosis in PLGC cells by regulating the miRNA-21/Bcl-2 signaling pathway.
Animals ; MicroRNAs/metabolism* ; Male ; Apoptosis/drug effects* ; Stomach Neoplasms/physiopathology* ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Rats ; Rats, Sprague-Dawley ; Drugs, Chinese Herbal/administration & dosage* ; Mitochondria/genetics* ; Signal Transduction/drug effects* ; Precancerous Conditions/drug therapy* ; Humans ; PTEN Phosphohydrolase/genetics*

OBJECTIVE: To investigate the effects of thymoquinone on the proliferation of acute myeloid leukemia (AML) cells and its molecular mechanism, so as to provide theoretical basis for the basic research on the anti-leukemia of traditional Chinese medicine. METHODS: The HL-60 and THP-1 cells were treated with thymoquinone at different concentration gradients, cell proliferation was detected by CCK-8 method, morphological changes were detected by Wright-Giemsa method, apoptosis was detected by Annexin V/PI double staining flow cytometry, and apoptosis and signal pathway protein expression were detected by Western blot. Real-time quantitative fluorescence PCR and Western blot were used to detect the expression changes of high mobility family members of SRY-related proteins (SOX). RESULTS: Thymoquinone inhibited the malignant proliferation of HL-60 and THP-1 cells, up-regulated the expression of pro-apoptotic protein Bax, down-regulated the expression of anti-apoptotic protein Bcl-2 and Survivin, and hydrolyzed Caspase-3 to induce the apoptosis of HL-60 and THP-1 cells. Thymoquinone could also significantly down-regulate the phosphorylation of PI3K, Akt and mTOR, and inhibit the malignant biological characteristics of HL-60 and THP-1 cells by inhibiting the activation of PI3K/Akt/mTOR pathway. After thymoquinone intervention in HL-60 and THP-1 cells, the expression of SOX2 and SOX4 could be down-regulated significantly. At low concentration ( < 10 μmol/L), the expression of SOX12 was weakly affected by thymoquinone. With increasing concentration, the expression of SOX12 could be down-regulated, however, thymoquinone had no effect on SOX11 expression. CONCLUSION Thymoquinone can inhibit the proliferation of AML cells, and its mechanism may be related to inhibiting the activation of PI3K/Akt/mTOR signaling pathway, regulating the expression of apoptotic proteins and core members of SOX family.
Humans ; Benzoquinones/pharmacology* ; Cell Proliferation/drug effects* ; Leukemia, Myeloid, Acute/metabolism* ; Apoptosis/drug effects* ; HL-60 Cells ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; bcl-2-Associated X Protein/metabolism* ; Cell Line, Tumor ; Phosphatidylinositol 3-Kinases/metabolism* ; THP-1 Cells

OBJECTIVE: To observe the effect of Guilu Taohong Formula on semen quality in varicocele (VC) models of rats, and to explore its possible mechanism. METHODS: Forty-eight male SD rats were randomly divided into four groups (sham group, model group, Guilu Taohong Formula group and L-carnitine group). After the establishment of models, the rats were treated with intragastric administration for eight consecutive weeks. The general condition of the rats was observed. After the gavage, the testicular and epididymal indices were calculated. Semen quality was assessed using an automatic semen analyzer. Apoptosis of testicular cells was assessed by TUNEL staining. And the expression levels of B-cell lymphocytoma-2 (Bcl-2), Bcl-2-associated X protein (Bax) and cysteine aspartate protease-3 (caspase-3) in testicular tissue were detected by Western blot. RESULTS: Compared with the sham group, testicular index, epididymal index, sperm concentration, the percentage of progressive motility of sperm (PR%) and the expression level of Bcl-2 decreased in model group(P<0.01). An increased apoptosis rate of spermatogenic cells and the expression levels of Bax and caspase-3 proteins were observed in model group as well(P<0.01). Compared with the model group, the testicular index, epididymal index, sperm concentration, PR% and the expression level of Bcl-2 in Guilu Taohong Formula group increased significantly (P<0.05, P<0.01). A decreased apoptosis rate of spermatogenic cells and the expression levels of Bax and caspase-3 proteins were detected in Guilu Taohong Formula group as well(P<0.01). Similarly, the L-carnitine group showed increased testicular index, epididymal index, sperm concentration, PR% and the expression level of Bcl-2 protein (P<0.05, P<0.01), where showed decreased apoptosis rate of spermatogenic cells and the expression levels of Bax and caspase-3 proteins compared with model group (P<0.01, P<0.05). CONCLUSION Guilu Taohong Formula improves semen quality in VC model rats and reduces the apoptosis rate of spermatogenic cells in testicular tissue, which may be related to the promotion of Bcl-2 protein expression and the inhibition of Bax and caspase-3 protein expression levels.
Male ; Animals ; Varicocele/drug therapy* ; Rats ; Apoptosis/drug effects* ; Rats, Sprague-Dawley ; Drugs, Chinese Herbal/therapeutic use* ; Semen Analysis ; bcl-2-Associated X Protein/metabolism* ; Caspase 3/metabolism* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Disease Models, Animal ; Spermatozoa/drug effects* ; Testis/drug effects*

OBJECTIVE: To explore the molecular mechanism of Shenmai Injection (SMI) against doxorubicin (DOX) induced cardiomyocyte apoptosis. METHODS: A total of 40 specific pathogen-free (SPF) male Sprague Dawley (SD) male rats were divided into 5 groups based on the random number table, including the control group, the model group, miR-30a agomir group, SMI low-dose (SMI-L) group, and SMI high-dose (SMI-H) group, with 8 rats in each group. Except for the control group, the rats were injected weekly with DOX (2 mg/kg) in the tail vein for 4 weeks to induce myocardial injury, and were given different regimens of continuous intervention for 2 weeks. Cardiac function was detected by echocardiography and myocardial pathological changes were observed by Van Gieson (VG) staining. Myocardial injury serum markers, including creatine kinase (CK), lactate dehydrogenase (LDH), troponin T (cTnT), N-terminal pro-brain natriuretic peptide (NT-proBNP), soluble ST2 (sST2), and growth differentiation factor-15 (GDF-15) were detected by enzyme linked immunosorbent assay (ELISA). Cardiomyocyte apoptosis was observed by terminal deoxynucleotidyl transferase-mediated biotinylated dUTP triphosphate nick end labeling (TUNEL) and transmission electron microscopy, and the expressions of target proteins and mRNA were detected by Western blot and quantitative real time polymerase chain reaction (qRT-RCR), respectively. RESULTS: The treatment with different doses of SMI reduced rat heart mass index and left ventricular mass index (P<0.05), significantly improved the left ventricular ejection fraction (P<0.05), decreased the levels of serum CK, LDH, cTnT, and NT-proBNP (P<0.05 or P<0.01), reduced the levels of serum sST2 and GDF-15 (P<0.05 or P<0.01), decreased the collagen volume fraction, reduced the expressions of rat myocardial type I and type III collagen (P<0.05 or P<0.01), and effectively alleviated myocardial fibrosis. And the study found that SMI promoted the expression levels of miR-30a and Bcl-2 in myocardium, and down-regulated the expression of Bax, which inhibited the activation of Caspase-3 and Caspase-9 (P<0.05 or P<0.01), and improved myocardial cell apoptosis. CONCLUSIONS SMI can alleviate myocardial injury and apoptosis caused by DOX, and its mechanism possibly by promoting the targeted expression of myocardial Bcl-2 protein through miR-30a.
Animals ; Myocytes, Cardiac/metabolism* ; Apoptosis/drug effects* ; MicroRNAs/genetics* ; Rats, Sprague-Dawley ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Doxorubicin/pharmacology* ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Drug Combinations ; Injections ; Rats

OBJECTIVES: Oxaliplatin (OXA) and 5-fluorouracil (5-FU) are 2 commonly used chemotherapeutic agents for colorectal cancer (CRC). MicroRNAs (miRNAs, miRs) play crucial roles in the development of chemoresistance in various cancers. However, the role and mechanism of miR-224-5p in regulating CRC chemoresistance remain unclear. This study aims to investigate the function of miR-224-5p in chemoresistant CRC cells and the underlying mechanisms. METHODS: CRC datasets GSE28702 and GSE69657 were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed miRNAs between drug-sensitive and resistant groups (OXA or 5-FU) were analyzed, and miR-224-5p was identified as the target miRNA. Chemoresistant cell lines HCT15-OXR, HCT15-5-FU, SW480-OXR, and SW480-5-FU were established. Transient transfections were performed using miR-224-5p mimics, inhibitors, and their respective negative controls (control mimic, control inhibitor) in these cell lines. Cells were treated with different concentrations of OXA or 5-FU post-transfection, and the half-maximal inhibitory concentration (IC₅₀) was determined using the cell counting kit-8 (CCK-8) assay. Cell proliferation was assessed by CCK-8 and colony formation assays. The expression levels of miR-224-5p, LC3, and P62 were measured by real-time polymerase chain reaction (real-time PCR) and/or Western blotting. Autophagic flux was assessed using a tandem fluorescent-tagged LC3 reporter assay. TargetScan 8.0, miRTarBase, miRPathDB, and HADb were used to predict B-cell lymphoma-2 (Bcl-2) as a potential miR-244-5p target, which was further validated by dual-luciferase reporter assays. RESULTS: Chemoresistant CRC cells exhibited down-regulated miR-224-5p expression, whereas up-regulation of miR-224-5p enhanced chemotherapy sensitivity. Exposure to OXA or 5-FU significantly increased autophagic activity in chemoresistant CRC cells, which was reversed by miR-224-5p overexpression. Dual-luciferase assays verified Bcl-2 as a direct target of miR-224-5p. CONCLUSIONS MiR-224-5p regulates chemoresistance in CRC by modulating autophagy through direct targeting of Bcl-2.
Humans ; MicroRNAs/physiology* ; Colorectal Neoplasms/drug therapy* ; Drug Resistance, Neoplasm/genetics* ; Autophagy/drug effects* ; Fluorouracil/pharmacology* ; Oxaliplatin ; Cell Line, Tumor ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Gene Expression Regulation, Neoplastic

OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies seen in clinic and requires novel treatment options. Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L., which exhibits an anti-cancer effect in multiple types of tumors. However, the therapeutic effect and underlying mechanism of morin in treating GC remains elusive. The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC. METHODS: For in vitro experiments, the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45, human gastric adenocarcinoma cell line AGS, and human gastric epithelial cell line GES-1; for apoptosis analysis, microscopic photography, Western blotting, ubiquitination analysis, quantitative polymerase chain reaction analysis, flow cytometry, and RNA interference technology were employed. For in vivo studies, immunohistochemistry, biomedical analysis, and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC. RESULTS: Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose- and time-dependent manner, but did not inhibit human gastric epithelial cells GES-1. Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells, suggesting that apoptosis was the main type of cell death during the treatment. Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells, which mainly relied on B cell leukemia/lymphoma 2 (BCL-2) associated agonist of cell death (BAD) but not phorbol-12-myristate-13-acetate-induced protein 1. The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD, rather than the transcription regulation and the phosphorylation of BAD. Furthermore, the combination of morin and BCL-2 inhibitor navitoclax (also known as ABT-737) produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals. In addition, morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway. CONCLUSION Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; 23(3): 320-332.
Humans ; Flavonoids/therapeutic use* ; Stomach Neoplasms/pathology* ; Animals ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Ubiquitination/drug effects* ; Mice ; Drug Synergism ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays ; Flavones

This paper investigated the mechanism of Huoxue Dingxuan Capsules(HXDX) on autophagy in vascular endothelial cells based on the "crosstalk" of Bcl-2 and mTOR protein. bEnd.3 cells were divided into a blank control group, a model group, and an HXDX group. CO-IP experiments were conducted, and then Western blot(WB) was used to detect the binding of Bcl-2 and mTOR. Co-localization of Bcl-2 with mTOR protein was observed by laser confocal microscopy after staining. The model of Bcl-2 siRNA in bEnd.3 cells was constructed, and the bEnd.3 cells were divided into five groups, including blank control group, oxygen-glucose deprivation(OGD) group, transfected Bcl-2 siRNA group, negative control(NC) group, and HXDX group. The model of mTOR siRNA in bEnd.3 cells was constructed, and the bEnd.3 cells were divided into five groups, including blank control group, OGD group, transfected mTOR siRNA group, NC group, and HXDX group. The expression of autophagy-related proteins was detected by WB. The results of CO-IP experiments showed that Bcl-2 and mTOR proteins could be co-localized and expressed in bEnd.3 cells, and the expression of Bcl-2 and mTOR proteins increased after the intervention of the HXDX-containing serum. After screening and transfection with Bcl-2-mus-384, autophagy of bEnd.3 cells was induced. The expression of Bcl-2 in the Bcl-2 siRNA group was significantly decreased compared with the blank control group and model group. The expression of mTOR protein was significantly lower than that of the OGD group, and the expression of human microtubule-associated protein light chain 3Ⅱ/Ⅰ was significantly higher than that of the model group. After the intervention of the HXDX-containing serum, the expression of Bcl-2 and mTOR was increased in the HXDX group compared with that in the Bcl-2 siRNA group, and the expression of LC3Ⅱ/LC3Ⅰ and Beclin1 was decreased in the HXDX group compared with that in the Bcl-2 siRNA group. After transfecting mTOR-mus-7061 and inducing autophagy of bEnd.3 cells, in the mTOR siRNA group, mTOR protein expression was decreased compared with the blank control and model groups, and LC3Ⅱ/LC3Ⅰ and Beclin1 protein expression was increased compared with the model group. After the intervention of the HXDX-containing serum, the expression of Bcl-2 and mTOR was increased in the HXDX group compared with that in the mTOR siRNA group, and the expression of LC3Ⅱ/LC3Ⅰ and Beclin1 proteins was decreased compared with the mTOR siRNA group. This study explored the "crosstalk" of Bcl-2 and mTOR during autophagy in bEnd.3 cells at the cellular level and illustrated the modulating effect of the HXDX-containing serum, which provided a basis for the treatment of cervical spondylosis of vertebral artery type.
Autophagy/drug effects* ; TOR Serine-Threonine Kinases/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Endothelial Cells/metabolism* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Animals ; Mice ; Capsules ; Humans

This study aimed to investigate the effect of aucubin(AU) on injury of nucleus pulposus cells and extracellular matrix(ECM) degradation and its mechanism. The nucleus pulposus cell injury model was established by interleukin-1β(IL-1β) and treated with AU or phosphatidylinositol 3-kinase(PI3K) inhibitor LY294002. CCK-8 experiment was conducted to test cell proliferation. EdU staining method was employed to detect cell injury. Flow cytometry was used to detect cell apoptosis. Western blot was used to detect protein levels of cleaved-caspase-3, B-cell lymphoma(Bcl-2), Bcl-2 associated X protein(Bax), type Ⅱ collagen(collagen Ⅱ), aggregation proteoglycans(aggrecan), PI3K, and mammalian target of rapamycin(mTOR). qPCR was used to detect the rRNA level of 5S, 18S, and 28S. Ethynyluridine was used to label nascent RNA. The results showed that IL-1β could significantly cause injury of nucleus pulposus cells and increase the apoptosis rate of nucleus pulposus cells and the expression of apoptosis protein cleaved-caspase-3 and Bax. At the same time, IL-1β down-regulated the expression of anti-apoptotic protein Bcl-2 and collagen Ⅱ and aggrecan, the main components of ECM. On this basis, AU intervention could improve the injury of nucleus pulposus cells, reduce the apoptosis of nucleus pulposus cells and the expression of cleaved-caspase-3 and Bax, and increase the expression of Bcl-2, collagen Ⅱ, and aggrecan. Compared with IL-1β, AU could up-regulate the phosphorylation level of PI3K and mTOR, and LY294002 could reverse the injury of nucleus pulposus cells and improve ECM degradation induced by AU. In addition, AU also could save lowered rRNA levels of 5S, 18S, and 28S induced by IL-1β and improve RNA synthesis. PI3K inhibitor LY294002 intervention could reduce the promoting effect of AU on ribosome biogenesis. The above results suggest that AU can improve the injury of nucleus pulposus cells and ECM degradation, and its mechanism of action is related to its activation of the PI3K/mTOR pathway to promote ribosome biogenesis.
Nucleus Pulposus/cytology* ; Extracellular Matrix/drug effects* ; Animals ; Iridoid Glucosides/pharmacology* ; Apoptosis/drug effects* ; Interleukin-1beta/metabolism* ; Phosphatidylinositol 3-Kinases/genetics* ; Rats ; Cell Proliferation/drug effects* ; TOR Serine-Threonine Kinases/genetics* ; Rats, Sprague-Dawley ; Humans ; Signal Transduction/drug effects* ; Caspase 3/genetics* ; Proto-Oncogene Proteins c-bcl-2/genetics*

This study aims to investigate the protective effect of resveratrol against liver injury in hindlimb unloading rats. Thirty 2-month-old male SD rats were randomly divided into normal group (Control), hindlimb unloading model group (Model), and hindlimb unloading+resveratrol administration group (Model+Res). The Model + Res group was injected intraperitoneally with 30 mg/kg of resveratrol, and the Control and Model groups were injected intraperitoneally with an equal volume of 0.9% NaCl. Liver tissues were collected after 28 days and analyzed for oxidative stress, inflammatory factors, energy metabolism indices, Na ⁺-K ⁺-ATPase and Ca ²⁺-Mg ²⁺-ATPase activity, and morphological changes were observed by hematoxylin-eosin staining. The protein expression levels of Bax, Bcl-2, p-PI3K, PI3K, p-AKT, and AKT were detected by Western blotting. Compared with the Control group, hepatocytes in the Model group showed swelling, abnormal morphology, nuclear consolidation, and cell membrane disruption. Oxidative stress, inflammatory factor levels, hepatic glycogen accumulation, and energy metabolism were increased in the liver tissues of the Model group, while resveratrol treatment significantly reversed these changes. The results of Western blotting showed that resveratrol significantly reduced the expression of Bax and increased the expression levels of Bcl-2, and the proteins of p-PI3K/PI3K and p-AKT/AKT expression levels. It is suggested that 28 days of hindlimb unloading treatment could lead to liver tissue injury in rats, which is manifested as oxidative stress, inflammatory response, energy metabolism disorder and increased apoptosis level, and resveratrol has a certain mitigating effect on this.
Animals ; Resveratrol ; Male ; Liver/pathology* ; Rats, Sprague-Dawley ; Rats ; Hindlimb Suspension ; Oxidative Stress/drug effects* ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Stilbenes/pharmacology* ; bcl-2-Associated X Protein/metabolism* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Apoptosis/drug effects*

OBJECTIVES: Hyperhomocysteinaemia (Hcy) is an independent risk factor for cardiovascular and cerebrovascular diseases. MicroRNA (miR)-18a-5p is closely related to cardiovascular diseases. This study aims to investigate the effects of miR-18a-5p on homocysteine (Hcy)-induced myocardial cells injury. METHODS: H9c2 cells were transfected with miR-18a-5p mimic/miR-18a-5p mimic negative control (NC) or combined with Hcy for intervention, and untreated cells were set as a control group. The transfection efficiency was verified by real-time RT-PCR, and cell counting kit-8 (CCK-8) assay was used to determine cell viability. Flow cytometry was used to detect apoptosis and reactive oxygen species (ROS) levels. Western blotting was performed to measure the protein levels of microtubule-associated protein 1 light chain 3 (LC3)-I, LC3-II, Beclin1, p62, Bax, Bcl-2, and Notch2. Dual luciferase reporter assay was used to detect the interaction of miR-18a-5p with Notch2. RESULTS: Compared with the control, treatment with Hcy or transfection with miR-18a-5p mimic alone, or combined treatment with Hcy and miR-18a-5p mimic/miR-18a-5p mimic NC significantly reduced the H9c2 cell viability, promoted apoptosis and ROS production, up-regulated the expressions of Bax and Beclin, down-regulated the expressions of Bcl-2, p62, and Notch2, and increased the ratio of LC3-II/LC3-I (all P<0.05). Compared with the combined intervention of miR-18a-5p mimic NC and Hcy group, the above indexes were more significantly changed in the combined intervention of miR-18a-5p mimic and Hcy group, and the difference between the 2 groups was statistically significant (all P<0.05). There is a targeted binding between Notch2 and miR-18a-5p. CONCLUSIONS MiR-18a-5p could induce autophagy and apoptosis via increasing ROS production in cardiomyocytes, and aggravate Hcy-induced myocardial injury. Notch2 is a target of miR-18a-5p.
Apoptosis/genetics* ; Autophagy/genetics* ; bcl-2-Associated X Protein ; MicroRNAs/metabolism* ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Reactive Oxygen Species ; Rats ; Animals ; Myocytes, Cardiac/drug effects* ; Homocysteine/adverse effects* ; Hyperhomocysteinemia