1.Bioinformatics Reveals Mechanism of Xiezhuo Jiedu Precription in Treatment of Ulcerative Colitis by Regulating Autophagy
Xin KANG ; Chaodi SUN ; Jianping LIU ; Jie REN ; Mingmin DU ; Yuan ZHAO ; Xiaomeng LANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):166-173
ObjectiveTo explore the potential mechanism of Xiezhuo Jiedu prescription in regulating autophagy in the treatment of ulcerative colitis (UC) by bioinformatics and animal experiments. MethodsThe differentially expressed genes (DEGs) in the colonic mucosal tissue of UC patients was obtained from the Gene Expression Omnibus (GEO), and those overlapped with autophagy genes were obtained as the differentially expressed autophagy-related genes (DEARGs). DEARGs were imported into Metascape and STRING, respectively, for gene ontology/Kyoto Encyclopedia of Genes and Genomics (GO/KEGG) enrichment analysis and protein-protein interaction (PPI) analysis. Finally, 15 key DEARGs were obtained. The core DEARGs were obtained by least absolute shrinkage and selection operator (LASSO) regression and receiver operating characteristic curve (ROC) analysis. The CIBERSORT deconvolution algorithm was used to analyze the immunoinfiltration of UC patients and the correlations between core DEARGs and immune cells. C57BL/6J mice were assigned into a normal group and a modeling group. The mouse model of UC was established by free drinking of 2.5% dextran sulfate sodium. The modeled mice were assigned into low-, medium-, and high-dose Xiezhuo Jiedu prescription and mesalazine groups according to the random number table method and administrated with corresponding agents by gavage for 7 days. The colonic mucosal morphology was observed by hematoxylin-eosin staining. The protein and mRNA levels of cysteinyl aspartate-specific proteinase 1 (Caspase-1), cathepsin B (CTSB), C-C motif chemokine-2 (CCL2), CXC motif receptor 4 (CXCR4), and hypoxia-inducing factor-1α (HIF-1α) in the colon tissue were determined by Western blot and real-time fluorescence quantitative polymerase chain reaction, respectively. ResultsThe dataset GSE87466 was screened from GEO and interlaced with autophagy genes. After PPI analysis, LASSO regression, and ROC analysis, the core DEARGs (Caspase-1, CCL2, CTSB, and CXCR4) were obtained. The results of immunoinfiltration analysis showed that the counts of NK cells, M0 macrophages, M1 macrophages, and dendritic cells in the colonic mucosal tissue of UC patients had significant differences, and core DEARGs had significant correlations with these immune cells. This result, combined with the prediction results of network pharmacology, suggested that the HIF-1α signaling pathway may play a key role in the regulation of UC by Xiezhuo Jiedu prescription. The animal experiments showed that Xiezhuo Jiedu prescription significantly alleviated colonic mucosal inflammation in UC mice. Compared with the normal group, the model group showed up-regulated protein and mRNA levels of caspase-1, CCL2, CTSB, CXCR4, and HIF-1α, which were down-regulated after treatment with Xiezhuo Jiedu prescription or mesalazine. ConclusionCaspase-1, CCL2, CTSB, and CXCR4 are autophagy genes that are closely related to the onset of UC. Xiezhuo Jiedu prescription can down-regulate the expression of core autophagy genes to alleviate the inflammation in the colonic mucosa of mice.
2.Predicting Postoperative Progression of Ossification of the Posterior Longitudinal Ligament in the Cervical Spine Using Interpretable Radiomics Models
Siyuan QIN ; Ruomu QU ; Ke LIU ; Ruixin YAN ; Weili ZHAO ; Jun XU ; Enlong ZHANG ; Feifei ZHOU ; Ning LANG
Neurospine 2025;22(1):144-156
Objective:
This study investigates the potential of radiomics to predict postoperative progression of ossification of the posterior longitudinal ligament (OPLL) after posterior cervical spine surgery.
Methods:
This retrospective study included 473 patients diagnosed with OPLL at Peking University Third Hospital between October 2006 and September 2022. Patients underwent posterior spinal surgery and had at least 2 computed tomography (CT) examinations spaced at least 1 year apart. OPLL progression was defined as an annual growth rate exceeding 7.5%. Radiomic features were extracted from preoperative CT images of the OPLL lesions, followed by feature selection using correlation coefficient analysis and least absolute shrinkage and selection operator, and dimensionality reduction using principal component analysis. Univariable analysis identified significant clinical variables for constructing the clinical model. Logistic regression models, including the Rad-score model, clinical model, and combined model, were developed to predict OPLL progression.
Results:
Of the 473 patients, 191 (40.4%) experienced OPLL progression. On the testing set, the combined model, which incorporated the Rad-score and clinical variables (area under the receiver operating characteristic curve [AUC] = 0.751), outperformed both the radiomics-only model (AUC = 0.693) and the clinical model (AUC = 0.620). Calibration curves demonstrated good agreement between predicted probabilities and observed outcomes, and decision curve analysis confirmed the clinical utility of the combined model. SHAP (SHapley Additive exPlanations) analysis indicated that the Rad-score and age were key contributors to the model’s predictions, enhancing clinical interpretability.
Conclusion
Radiomics, combined with clinical variables, provides a valuable predictive tool for assessing the risk of postoperative progression in cervical OPLL, supporting more personalized treatment strategies. Prospective, multicenter validation is needed to confirm the utility of the model in broader clinical settings.
3.Predicting Postoperative Progression of Ossification of the Posterior Longitudinal Ligament in the Cervical Spine Using Interpretable Radiomics Models
Siyuan QIN ; Ruomu QU ; Ke LIU ; Ruixin YAN ; Weili ZHAO ; Jun XU ; Enlong ZHANG ; Feifei ZHOU ; Ning LANG
Neurospine 2025;22(1):144-156
Objective:
This study investigates the potential of radiomics to predict postoperative progression of ossification of the posterior longitudinal ligament (OPLL) after posterior cervical spine surgery.
Methods:
This retrospective study included 473 patients diagnosed with OPLL at Peking University Third Hospital between October 2006 and September 2022. Patients underwent posterior spinal surgery and had at least 2 computed tomography (CT) examinations spaced at least 1 year apart. OPLL progression was defined as an annual growth rate exceeding 7.5%. Radiomic features were extracted from preoperative CT images of the OPLL lesions, followed by feature selection using correlation coefficient analysis and least absolute shrinkage and selection operator, and dimensionality reduction using principal component analysis. Univariable analysis identified significant clinical variables for constructing the clinical model. Logistic regression models, including the Rad-score model, clinical model, and combined model, were developed to predict OPLL progression.
Results:
Of the 473 patients, 191 (40.4%) experienced OPLL progression. On the testing set, the combined model, which incorporated the Rad-score and clinical variables (area under the receiver operating characteristic curve [AUC] = 0.751), outperformed both the radiomics-only model (AUC = 0.693) and the clinical model (AUC = 0.620). Calibration curves demonstrated good agreement between predicted probabilities and observed outcomes, and decision curve analysis confirmed the clinical utility of the combined model. SHAP (SHapley Additive exPlanations) analysis indicated that the Rad-score and age were key contributors to the model’s predictions, enhancing clinical interpretability.
Conclusion
Radiomics, combined with clinical variables, provides a valuable predictive tool for assessing the risk of postoperative progression in cervical OPLL, supporting more personalized treatment strategies. Prospective, multicenter validation is needed to confirm the utility of the model in broader clinical settings.
4.Predicting Postoperative Progression of Ossification of the Posterior Longitudinal Ligament in the Cervical Spine Using Interpretable Radiomics Models
Siyuan QIN ; Ruomu QU ; Ke LIU ; Ruixin YAN ; Weili ZHAO ; Jun XU ; Enlong ZHANG ; Feifei ZHOU ; Ning LANG
Neurospine 2025;22(1):144-156
Objective:
This study investigates the potential of radiomics to predict postoperative progression of ossification of the posterior longitudinal ligament (OPLL) after posterior cervical spine surgery.
Methods:
This retrospective study included 473 patients diagnosed with OPLL at Peking University Third Hospital between October 2006 and September 2022. Patients underwent posterior spinal surgery and had at least 2 computed tomography (CT) examinations spaced at least 1 year apart. OPLL progression was defined as an annual growth rate exceeding 7.5%. Radiomic features were extracted from preoperative CT images of the OPLL lesions, followed by feature selection using correlation coefficient analysis and least absolute shrinkage and selection operator, and dimensionality reduction using principal component analysis. Univariable analysis identified significant clinical variables for constructing the clinical model. Logistic regression models, including the Rad-score model, clinical model, and combined model, were developed to predict OPLL progression.
Results:
Of the 473 patients, 191 (40.4%) experienced OPLL progression. On the testing set, the combined model, which incorporated the Rad-score and clinical variables (area under the receiver operating characteristic curve [AUC] = 0.751), outperformed both the radiomics-only model (AUC = 0.693) and the clinical model (AUC = 0.620). Calibration curves demonstrated good agreement between predicted probabilities and observed outcomes, and decision curve analysis confirmed the clinical utility of the combined model. SHAP (SHapley Additive exPlanations) analysis indicated that the Rad-score and age were key contributors to the model’s predictions, enhancing clinical interpretability.
Conclusion
Radiomics, combined with clinical variables, provides a valuable predictive tool for assessing the risk of postoperative progression in cervical OPLL, supporting more personalized treatment strategies. Prospective, multicenter validation is needed to confirm the utility of the model in broader clinical settings.
5.Predicting Postoperative Progression of Ossification of the Posterior Longitudinal Ligament in the Cervical Spine Using Interpretable Radiomics Models
Siyuan QIN ; Ruomu QU ; Ke LIU ; Ruixin YAN ; Weili ZHAO ; Jun XU ; Enlong ZHANG ; Feifei ZHOU ; Ning LANG
Neurospine 2025;22(1):144-156
Objective:
This study investigates the potential of radiomics to predict postoperative progression of ossification of the posterior longitudinal ligament (OPLL) after posterior cervical spine surgery.
Methods:
This retrospective study included 473 patients diagnosed with OPLL at Peking University Third Hospital between October 2006 and September 2022. Patients underwent posterior spinal surgery and had at least 2 computed tomography (CT) examinations spaced at least 1 year apart. OPLL progression was defined as an annual growth rate exceeding 7.5%. Radiomic features were extracted from preoperative CT images of the OPLL lesions, followed by feature selection using correlation coefficient analysis and least absolute shrinkage and selection operator, and dimensionality reduction using principal component analysis. Univariable analysis identified significant clinical variables for constructing the clinical model. Logistic regression models, including the Rad-score model, clinical model, and combined model, were developed to predict OPLL progression.
Results:
Of the 473 patients, 191 (40.4%) experienced OPLL progression. On the testing set, the combined model, which incorporated the Rad-score and clinical variables (area under the receiver operating characteristic curve [AUC] = 0.751), outperformed both the radiomics-only model (AUC = 0.693) and the clinical model (AUC = 0.620). Calibration curves demonstrated good agreement between predicted probabilities and observed outcomes, and decision curve analysis confirmed the clinical utility of the combined model. SHAP (SHapley Additive exPlanations) analysis indicated that the Rad-score and age were key contributors to the model’s predictions, enhancing clinical interpretability.
Conclusion
Radiomics, combined with clinical variables, provides a valuable predictive tool for assessing the risk of postoperative progression in cervical OPLL, supporting more personalized treatment strategies. Prospective, multicenter validation is needed to confirm the utility of the model in broader clinical settings.
6.Predicting Postoperative Progression of Ossification of the Posterior Longitudinal Ligament in the Cervical Spine Using Interpretable Radiomics Models
Siyuan QIN ; Ruomu QU ; Ke LIU ; Ruixin YAN ; Weili ZHAO ; Jun XU ; Enlong ZHANG ; Feifei ZHOU ; Ning LANG
Neurospine 2025;22(1):144-156
Objective:
This study investigates the potential of radiomics to predict postoperative progression of ossification of the posterior longitudinal ligament (OPLL) after posterior cervical spine surgery.
Methods:
This retrospective study included 473 patients diagnosed with OPLL at Peking University Third Hospital between October 2006 and September 2022. Patients underwent posterior spinal surgery and had at least 2 computed tomography (CT) examinations spaced at least 1 year apart. OPLL progression was defined as an annual growth rate exceeding 7.5%. Radiomic features were extracted from preoperative CT images of the OPLL lesions, followed by feature selection using correlation coefficient analysis and least absolute shrinkage and selection operator, and dimensionality reduction using principal component analysis. Univariable analysis identified significant clinical variables for constructing the clinical model. Logistic regression models, including the Rad-score model, clinical model, and combined model, were developed to predict OPLL progression.
Results:
Of the 473 patients, 191 (40.4%) experienced OPLL progression. On the testing set, the combined model, which incorporated the Rad-score and clinical variables (area under the receiver operating characteristic curve [AUC] = 0.751), outperformed both the radiomics-only model (AUC = 0.693) and the clinical model (AUC = 0.620). Calibration curves demonstrated good agreement between predicted probabilities and observed outcomes, and decision curve analysis confirmed the clinical utility of the combined model. SHAP (SHapley Additive exPlanations) analysis indicated that the Rad-score and age were key contributors to the model’s predictions, enhancing clinical interpretability.
Conclusion
Radiomics, combined with clinical variables, provides a valuable predictive tool for assessing the risk of postoperative progression in cervical OPLL, supporting more personalized treatment strategies. Prospective, multicenter validation is needed to confirm the utility of the model in broader clinical settings.
7.Impact of the number of microsatellite markers on the analysis of population genetic diversity of Schistosoma japonicum
Juan LONG ; Lang MA ; Hongying ZONG ; Zhipeng ZHOU ; Hao YAN ; Qinping ZHAO
Chinese Journal of Schistosomiasis Control 2025;37(3):239-246
Objective To examine the impact of different numbers of microsatellite markers on the analysis of population genetic diversity of Schistosoma japonicum, so as to provide insights into studies on the population genetic diversity of S. japonicum. Methods Oncomelania hupensis snails were collected from a wasteland in Gong’an County, Hubei Province, and 37 S. japonicum-infected O. hupensis snails were identified using the cercarial shedding method. A single cercaria released from each S. japonicum-infected O. hupensis snail was collected, and 10 cercariae were randomly collected from DNA extraction. Nine previously validated microsatellite loci and 15 additional microsatellite loci screened from literature review and the GenBank database and confirmed with stable amplification efficiency were selected as molecular markers. Genomic DNA from cercariae was subjected to three multiplex PCR amplifications of microsatellite markers with the Type-it Microsatellite PCR kit, and genotyped using capillary electrophoresis. The population genetic diversity of S. japonicum cercariae DNA was analyzed with observed number of alleles (Na), effective number of alleles (Ae), observed heterozygosity (Ho), expected heterozygosity (He), and polymorphism information content (PIC), and tested for Hardy-Weinberg equilibrium (HWE) and linkage disequilibrium (LD). To further investigate the impact of the number of microsatellite loci on the population genetic diversity of S. japonicum, the number of microsatellite markers was sequentially assigned from 1 to 24, and the mean and standard deviation of Na were calculated for S. japonicum populations at different locus numbers. In addition, the coefficient of variation (CV) of allelic number (defined as the ratio of the standard deviation to the mean) was determined, and the variation in Na with increasing microsatellite locus numbers was analyzed. Results Genomic DNA from 345 S. japonicum cercariae was selected for genotyping of 24 microsatellite markers, and all 24 microsatellite loci met linkage equilibrium (standardized linkage disequilibrium coefficient D′ < 0.7, r2 < 0.3) and deviated from Hardy-Weinberg equilibrium (P < 0.001). The mean Na, Ae, Ho and He were 27.46 ± 2.18, 12.46 ± 0.95, 0.46 ± 0.03, and 0.91 ± 0.01 for 24 microsatellite loci in S. japonicum cercarial populations, respectively, and PIC ranged from 0.85 to 0.96, indicating high genome-wide representativeness of 24 microsatellite loci. The mean value of Na-Ae was higher in genotyping with 9 previously validated microsatellite loci (19.88 ± 8.43) than with all 24 loci (14.99 ± 8.09). As the number of microsatellite loci increased, the mean Na showed no significant variation; however, the standard deviation gradually decreased. Notably, if the locus number reached 18 or more, the variation in the standard deviation of Na remarkably reduced. In addition, the standard deviation of Na at 18 loci was less than 5% of the mean Na at 24 loci, with a CV of 4.6%. Conclusions The number of microsatellite loci significantly affects the population genetic diversity analysis of S. japonicum. Eighteen or more microsatellite loci are recommended for analysis of the population genetic diversity of S. japonicum under the current conditions of low-prevalence infection and unbalanced genetic distribution of S. japonicum.
8.Mechanism of Xiezhuo Jiedu Recipe Regulating Ferroptosis in Treatment of Ulcerative Colitis Based on Bioinformatics and Animal Experiments
Chaodi SUN ; Jianping LIU ; Mingmin DU ; Xin KANG ; Jiancong CUI ; Yuan ZHAO ; Sujie JIA ; Xiaomeng LANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(11):166-173
ObjectiveThe bioinformatics method was used to screen ferroptosis differential genes (FRGs) closely related to ulcerative colitis (UC), and animal experiments were conducted to verify whether the mechanism of Xiezhuo Jiedu recipe in treating UC is related to the regulation of ferroptosis. MethodThe differentially expressed genes (DEGs) of colonic mucosa tissue of UC patients were obtained from the GEO database, and the intersection of the genes with ferroptosis genes was used to obtain FRGs. The core FRGs were obtained by cluster analysis, minimum absolute contraction and selection operator (LASSO) regression, and receiver operating characteristic curve (ROC) curve analysis. In animal experiments, the UC mouse model was prepared by making the mouse freely drink 2.5% dextran sodium sulfate (DSS). Xiezhuo Jiedu recipe and mesalazine were given by gavage for seven days, and the inflammatory infiltration of colonic mucosa was observed by hematoxylin-eosin (HE) staining. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression levels of E3 ubiquitin ligase (FBXW7), zinc finger protein (ZFP36), solute carrier family 7 member 11 (SLC7A11), and Toll-like receptor 4 (TLR4) in colon tissue. The protein expression levels of FBXW7, ZFP36, SLC7A11, and TLR4 in colon tissue were detected by Western blot. ResultDataset GSE87466 was screened from the GEO database, and its intersections with the ferroptosis gene were analyzed to obtain 21 FRGs. After cluster analysis, LASSO regression, and ROC analysis, core FRGs (FBXW7, ZFP36, SLC7A11, and TLR4) were obtained. Immunoinfiltration analysis showed significant differences in the expression of initial B cells, M1 macrophages, plasma cells, and M2 macrophages in the colonic mucosa tissue of UC mice, and there was a significant correlation between core FRGs and these immune cells. Further animal experiments showed that the colonic mucosa tissue of mice in the model group was disorganized and infiltrated by a large number of inflammatory cells. The inflammation of the colonic mucosa tissue of mice in each group was relieved to varying degrees after treatment with Xiezhuo Jiedu recipe and mesalazine, while the colonic mucosa tissue of mice in the high-dose group of Xiezhuo Jiedu recipe showed almost no inflammatory changes. Compared with the normal group, the protein and mRNA expressions of FBXW7, ZFP36, SLC7A11, and TLR4 in the model group were significantly increased, and the expression of core FRGs in colonic mucosa tissue of mice in all groups was significantly down-regulated after treatment with Xiezhuo Jiedu recipe and mesalazine. ConclusionFBXW7, ZFP36, SLC7A11, and TLR4 are ferroptosis genes closely related to the pathogenesis of UC, and Xiezhuo Jiedu recipe can significantly alleviate colonic mucosa inflammation in mice by down-regulating core ferroptosis genes.
9.Improvement of Colonic Mucosa Inflammatory Response in Mice with Ulcerative Colitis by Xiezhuo Jiedu Recipe Through miRNA-155-5p/JAK2/STAT3 Pathway
Chaodi SUN ; Mengmeng ZHAO ; Xiaomeng LANG ; Jie REN ; Xin KANG ; Jiancong CUI ; Sujie JIA ; Yujing MA ; Yue LIU ; Qiang CHUAI ; Wenjing ZHAI ; Jianping LIU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(11):174-182
ObjectiveThe differential expression of microRNAs (miRNAs) between the active stage and the remission stage of ulcerative colitis (UC) was analyzed by bioinformatics method, and the regulatory relationship was constructed by screening the differentially expressed genes (DEGs). The mechanism of Xizhuo Jiedu recipe in the treatment of UC was speculated and verified by animal experiments. MethodThe miRNAs data set of colonic mucosa tissue of UC patients was obtained from the gene expression database (GEO), and the most differentially expressed miRNAs were screened by GEO2R, Excel, and other tools as research objects. TargetScan, miRTarbase, miRDB, STRING, TRRUST, and Matescape databases were used to screen key DEGs, predict downstream transcription factors (TFs), gene ontology (GO), and conduct Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The key signaling pathways were selected for animal experiments. In animal experiments, the UC mouse model was prepared by making the mouse freely drink 2.5% dextran sodium sulfate (DSS). Xiezhu Jiedu recipe and mesalazine were given by gavage for seven days, and the inflammatory infiltration of colonic mucosa was observed by hematoxylin-eosin (HE) staining. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of miR-155-5p in colon tissue. Immunohistochemistry and Western blot were used to detect the protein expression levels of cytokine signal transduction inhibitor (SOCS1), phosphorylated transcriptional signal transductor and activator 3 (p-STAT3), phosphorylated Janus kinase 2 (p-JAK2), and retinoic acid-associated orphan receptor-γt (ROR-γt). The expression levels of transforming growth factor-β (TGF-β), interleukin-17 (IL-17), interleukin-6 (IL-6), and interleukin-10 (IL-10) in serum were detected by enzyme linked immunosorbent assay (ELISA). ResultThe GSE48957 dataset was screened from the GEO database, and miR-155-5p was selected as the research object from the samples in the active and remission stages. 131 DEGs were screened. The GO/KEGG enrichment analysis was closely related to biological processes such as positive regulation of miRNA transcription and protein phosphorylation, as well as signaling pathways such as stem cell signaling pathway, IL-17 signaling pathway, and helper T cell 17 (Th17) cell differentiation. The Matescape database was used to screen out 10 key DEGs, among which SOCS1 was one of the key DEGs of miR-155-5p. Further screening of the TFS of key DEGs revealed that STAT3 was one of the main TFs of SOCS1. The results of animal experiments showed that Xiezhu Jiedu Recipe could effectively down-regulate the mRNA expression of miR-155-5p and protein expression of p-STAT3, p-JAK2, and ROR-γt in colon tissue of UC mice and the expression of IL-17 and IL-6 in serum of UC mice, up-regulate the protein expression of SOCS1 and the expression of TGF-β and IL-10, increase the level of anti-inflammatory factors, and reduce inflammatory cell infiltration. ConclusionIt is speculated that Xizhuo Jiedu recipe may interfere with SOCS1 by regulating the expression of miR-155-5p in UC mice, inhibit the phosphorylation of STAT3, inhibit the differentiation of CD4+ T cells into Th17 cells, reduce the levels of pro-inflammatory factors (IL-17 and IL-6), and increase the levels of anti-inflammatory factors (TGF-β and IL-10). As a result, the inflammation of colon mucosa in UC mice was alleviated.
10.Spermidine alleviates pressure overload-induced heart failure in mice via improving cardiac mitochondrial energy metabolism
Xiaoliang ZHANG ; Xiaoling ZHAO ; Jing GENG ; Lang HU ; Yan LI
Chinese Journal of Pathophysiology 2024;40(2):193-203
AIM:To investigate the effect of spermidine(SPD)on pressure overload-induced cardiac hyper-trophy and heart failure model in mice and its underlying mechanisms.METHODS:(1)Eight-week-old male C57BL/6J mice were randomly divided into 4 groups:sham group,sham+SPD group,transverse aortic constriction(TAC)group,and TAC+SPD group.After TAC,the mice in sham+SPD group and TAC+SPD group were fed with 3 mmol/L SPD via drinking water,and the mice in other groups were fed with normal water.Western blot was used to detect the protein ex-pression levels of silent information regulator 6(SIRT6),peroxisome proliferator-activated receptor γ coactivator-1(PGC-1)and mitofusin 2(MFN2).Adult mouse cardiomyocytes were isolated to detect cell length and width.Wheat germ agglu-tinin staining was used to detect the cardiac cell size.Masson staining was used to detect the extent of fibrosis.Echocar-diography was used to detect cardiac function and myocardial hypertrophy.Transmission electron microscopy was used to analyze mitochondrial morphology.Oxygraph-2k high-resolution respirometer was used to detect cardiac mitochondrial oxy-gen consumption.(2)In vitro,primary rat ventricular cardiomyocytes were cultured and treated with angiotensin II(Ang II;1 μmol/L)to construct a hypertrophy model of cardiomyocytes.These cardiomyocytes were divided into control(Con)group,Con+SPD(1 mmol/L)group,Ang II group,Ang II+SPD group and Ang II+SPD+SIRT6 siRNA(siSIRT6)group.Confocal microscopy was used to detect cardiomyocytes area and mitochondrial.RESULTS:(1)Compared with sham group,cardiac function of the mice in TAC group was significantly decreased(P<0.05),the degree of myocardial hyper-trophy was significantly increased(P<0.05),and the expression levels of SIRT6,PGC-1 and MFN2 in the myocardial tis-sue were significantly decreased(P<0.05).Compared with TAC group,the expression levels of SIRT6,PGC-1 and MFN2 in mouse myocardial tissues of TAC+SPD group were significantly increased(P<0.05),pathological myocardial hy-pertrophy was reduced(P<0.05),the numbers of mitochondria and mitochondrial cristae were increased(P<0.05),mito-chondrial function was restored(P<0.05),myocardial fibrosis was alleviated(P<0.05),and cardiac function was im-proved(P<0.05).(2)In vitro,compared with Con group,the expression levels of SIRT6,PGC-1 and MFN2 in cardio-myocytes of Ang II group were decreased(P<0.05),and the degree of cardiomyocyte hypertrophy was significantly in-creased(P<0.05).Treatment with SPD increased the expression levels of SIRT6,PGC-1 and MFN2 in cardiomyocytes of Ang II group(P<0.05),reversed myocardial hypertrophy and improved mitochondrial dynamics(P<0.05).Compared with Ang II group,the expression levels of SIRT6,PGC-1 and MFN2 in Ang II+SPD+siSIRT6 group showed no significant changes,and the degree of cardiomyocyte hypertrophy and mitochondrial dynamics also had no statistically significant changes.CONCLUSION:Spermidine promotes the expression of SIRT6,PGC-1 and MFN2,thus improving mitochon-drial function,reducing myocardial hypertrophy and alleviating heart failure in mice with pressure overload.

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