1.Bidirectional association between metabolic associated fatty liver disease and the risk of atherosclerotic cardiovascular disease
Yanan ZHAO ; Qi QI ; Xinyu WU ; Quanle HAN ; Jing YANG ; Boheng ZHANG ; Xuyang LI ; Lei LI ; Yun ZHANG ; Shouling WU ; Kangbo LI
Journal of Clinical Hepatology 2026;42(4):856-865
ObjectiveTo investigate the association between metabolic associated fatty liver disease (MAFLD) and the risk of atherosclerotic cardiovascular disease (ASCVD), and to provide data support for the prevention and treatment of such metabolic-associated diseases in clinical practice. MethodsAn observation cohort was established for the workers of Kailuan who underwent physical examination for the first time from June 2006 to October 2007 and had complete liver assessment data, without the history of malignant tumor, MAFLD or ASCVD. According to the presence or absence of MAFLD, the patients were divided into non-MAFLD group with 67 565 patients and MAFLD group with 29 004 patients, and according to the presence or absence of ASCVD, the patients were divided into non-ASCVD group with 69 141 patients and ASCVD group with 481 patients. The group t-test or the Wilcoxon rank-sum test was used for comparison of continuous data between the two groups. The
2.Influencing factors of work-related musculoskeletal disorders in neck, shoulder, and lumbar regions among workers wearing insulated gloves in power grid industry
Xuyang LIAO ; Zekai LIANG ; Qingsong CHEN ; Chunguang DING ; Runkun ZHANG ; Guanlin LI
Journal of Environmental and Occupational Medicine 2026;43(5):591-596
Background As one of the primary operational methods in the power grid industry, the insulated glove working method imposes significant physical demands due to the constraints of insulating equipment and specific required postures, resulting in substantial occupational health hazards among workers in this sector, which have garnered widespread social attention. Objective To investigate the prevalence and influencing factors of work-related musculoskeletal disorders (WMSDs) in the neck, shoulder, and lumbar regions among workers wearing insulated gloves, and to provide targeted measures to reduce occupational hazards. Methods Using stratified cluster sampling, 1079 frontline workers were randomly selected from power supply enterprises across 3 provinces in China. The revised Chinese version of the Musculoskeletal Disorders Questionnaire was used to investigate the 1-year prevalence of WMSDs in the neck, shoulder, and lumbar regions among workers wearing insulated gloves, and to collect factors associated with multi-site WMSDs (defined as involvement of ≥2 sites among the neck, shoulder, and lumbar). Results The 1-year prevalence of WMSDs in the neck, shoulder, and lumbar regions was 39.9%, 30.0%, and 25.3%, respectively, with a multi-site WMSDs prevalence of 32.0%. Multiple logistic regression analysis showed that, compared to workers with technical secondary school education or senior high school education and below, workers with junior college education or bachelor’s degrees and above had a higher risk of multi-site WMSDs (OR=2.12, 95%CI: 1.47, 3.06). Compared to workers with <10 years of work experience, those with 10-<20 years of work experience had a higher risk of multi-site WMSDs (OR=1.96, 95%CI: 1.45, 2.67). Working in uncomfortable postures "sometimes" (OR=1.64, 95%CI: 1.14, 2.36), "frequently" (OR=2.75, 95%CI: 1.76, 4.29), and "very frequently" (OR=3.55, 95%CI: 2.04, 6.19) were significantly associated with an increased risk of multi-site WMSDs compared to never working in such postures. Frequent repetitive movements of the low back (OR=2.05, 95%CI: 1.48, 2.84) increased the risk of multi-site WMSDs, while sufficient rest time decreased the risk (OR=0.45, 95%CI: 0.34, 0.61). Conclusion The prevalences of single-site and multi-site WMSDs in the neck, shoulder, lumbar regions are relatively high among workers wearing insulated gloves. Factors associated with multi-site WMSDs include 10-<20 years of work experience, junior college education or bachelor’s degrees and above, uncomfortable working postures, frequent repetitive low-back movements, and lack of sufficient rest time.
3.A panel study on association of short-term air pollution exposure and peripheral blood microparticles in healthy adults
Bin ZHANG ; Xinghou HE ; Jiahui LIU ; Xuyang SHAN ; Yan FANG ; Huiying XU ; Erlu ZHAO ; Shengcong LIU ; Hongbing XU ; Jianping LI ; Wei HUANG
Journal of Environmental and Occupational Medicine 2026;43(1):1-7
Background Microparticles (MPs) are one of the main medium of inflammatory reaction with an important role in atherosclerotic progression. Studies on association of air pollution exposure and levels of peripheral blood MPs are limited among human. Objective To evaluate the effects of short-term exposure to air pollution on levels of peripheral blood MPs. Method A panel of 73 healthy adults was followed with 4 repeated follow-ups in Beijing, China, from November 2014 to January 2016. During each visit, we collected questionnaire information, fasting venous blood, urine, and exposures to fine particulate matter (PM2.5), black carbon, nitric oxide, nitrogen dioxide, nitrogen oxide, sulfur dioxide, carbon monoxide, and ozone. We used linear mixed-effect models to analyze associations of air pollution exposure with levels of total MPs (TMPs) and MPs derived from various cells. Stratified analysis was conducted by levels of C-reactive protein (CRP) and malondialdehyde (MDA). Results The results showed significant associations between air pollution exposure and peripheral blood TMPs at 2 h-6 d prior to the follow-ups (P<0.05), while no statistical associations were found for MPs derived from different cell types. Significant increases in TMPs of 7.8% (95%CI: 0.7%, 15.3%) and 14.3% (95%CI: 2.8%, 27.2%) were observed with each interquartile range (IQR) increase in PM2.5 (IQR=64.9 μg·m−3) at prior 18 h and NO (IQR=40.5 μg·m−3) at prior 48 h. Among participants with low levels of CRP and MDA, significantly positive associations were observed between air pollution exposure and levels of TMPs (P<0.05). Conclusion Short-term exposure to air pollution is significantly associated with increased levels of circulating MPs in healthy adults, and in people with lower systemic inflammation, peripheral blood MPs levels are more easily affected after exposure to air pollutants.
4.Influencing factors of work-related musculoskeletal disorders in neck, shoulder, and lumbar regions among workers wearing insulated gloves in power grid industry
Xuyang LIAO ; Zekai LIANG ; Qingsong CHEN ; Chunguang DING ; Runkun ZHANG ; Guanlin LI
Journal of Environmental and Occupational Medicine 2026;43(5):591-596
Background As one of the primary operational methods in the power grid industry, the insulated glove working method imposes significant physical demands due to the constraints of insulating equipment and specific required postures, resulting in substantial occupational health hazards among workers in this sector, which have garnered widespread social attention. Objective To investigate the prevalence and influencing factors of work-related musculoskeletal disorders (WMSDs) in the neck, shoulder, and lumbar regions among workers wearing insulated gloves, and to provide targeted measures to reduce occupational hazards. Methods Using stratified cluster sampling, 1079 frontline workers were randomly selected from power supply enterprises across 3 provinces in China. The revised Chinese version of the Musculoskeletal Disorders Questionnaire was used to investigate the 1-year prevalence of WMSDs in the neck, shoulder, and lumbar regions among workers wearing insulated gloves, and to collect factors associated with multi-site WMSDs (defined as involvement of ≥2 sites among the neck, shoulder, and lumbar). Results The 1-year prevalence of WMSDs in the neck, shoulder, and lumbar regions was 39.9%, 30.0%, and 25.3%, respectively, with a multi-site WMSDs prevalence of 32.0%. Multiple logistic regression analysis showed that, compared to workers with technical secondary school education or senior high school education and below, workers with junior college education or bachelor’s degrees and above had a higher risk of multi-site WMSDs (OR=2.12, 95%CI: 1.47, 3.06). Compared to workers with <10 years of work experience, those with 10-<20 years of work experience had a higher risk of multi-site WMSDs (OR=1.96, 95%CI: 1.45, 2.67). Working in uncomfortable postures "sometimes" (OR=1.64, 95%CI: 1.14, 2.36), "frequently" (OR=2.75, 95%CI: 1.76, 4.29), and "very frequently" (OR=3.55, 95%CI: 2.04, 6.19) were significantly associated with an increased risk of multi-site WMSDs compared to never working in such postures. Frequent repetitive movements of the low back (OR=2.05, 95%CI: 1.48, 2.84) increased the risk of multi-site WMSDs, while sufficient rest time decreased the risk (OR=0.45, 95%CI: 0.34, 0.61). Conclusion The prevalences of single-site and multi-site WMSDs in the neck, shoulder, lumbar regions are relatively high among workers wearing insulated gloves. Factors associated with multi-site WMSDs include 10-<20 years of work experience, junior college education or bachelor’s degrees and above, uncomfortable working postures, frequent repetitive low-back movements, and lack of sufficient rest time.
5.Proximal pericolic lymph node metastasis beyond 10 cm in rectal cancer: patterns of prognostic impact of extended resection in a prospective cohort study
Xuyang YANG ; Yang ZHANG ; Lina YE ; Qingbin WU ; Tinghan YANG ; Mingtian WEI ; Xiangbing DENG ; Haining CHEN ; Wenjian MENG ; Ziqiang WANG
Chinese Journal of Gastrointestinal Surgery 2025;28(9):1015-1025
Objective:To determine the actual metastasis rate of paracolic lymph nodes (PCN) more than 10 cm proximal to rectal tumors and explore the significance of PCN dissection in the prognosis of patients with rectal cancer. ?Methods:This was a prospective observational cohort study. The clinical data of 457 consecutive patients with rectal cancer who underwent radical surgery at the Colorectal Tumor Center of West China Hospital, Sichuan University from January 2015 to May 2022 were included. Inclusion criteria: (1) Pathologically confirmed rectal adenocarcinoma (anal margin ≤ 12 cm); (2) R0 resection was performed with a proximal margin ≥ 10 cm (measured on the in vivo specimen during surgery after intestinal mobilization); (3) For stage IV patients, only those with resectable metastatic lesions by R0 were included; (4) Patients who completed the full course of neoadjuvant therapy (TNT) must meet the surgical window of 8-12 weeks after radiotherapy. Exclusion criteria: tumors located more than 15 cm from the anal margin, synchronous multiple primary colorectal cancers, positive tumor margins, preoperative imaging suggesting lateral lymph node metastasis (LLNM), presence of Lynch syndrome or familial adenomatous polyposis, emergency surgery, recurrence after rectal cancer surgery, T4b tumors requiring combined organ resection, previous radiotherapy and chemotherapy for non-rectal cancer, and those with cardiac, pulmonary, renal and other organ dysfunction that could not tolerate surgery. After standard total mesorectal excision (TME), the proximal intestinal tube was transected at a level more than 10 cm above the lesion, and then intestinal anastomosis or enterostomy was completed. The distance from the tumor edge was marked and measured in vivo during the operation, and lymph nodes were harvested from the fresh specimen. Patients with PCN metastasis beyond 10 cm proximal to the tumor were classified into the positive lymph node group (pPCN group), while those without PCN metastasis beyond 10 cm proximal to the tumor were classified into the negative lymph node group (nPCN group). The differences in clinicopathological characteristics, overall survival (OS) and disease-free survival (DFS) between the two groups were compared, and risk factor analysis and survival analysis of pPCN were performed.Results:There were 16 cases (3.5%) in the pPCN group, 15 cases (3.3%) had central lymph node metastasis; the nPCN group included 441 cases. When comparing the baseline characteristics between the pPCN group and the nPCN group, there was no statistically significant difference in other aspects except that the cN stage was more advanced in the pPCN group ( P=0.006) (all P>0.05). The number of positive mesenteric lymph nodes in the pPCN group was higher than that in the nPCN group ( P<0.001), and the proportion of patients with a total number of harvested lymph nodes ≥12 and the number of lymph nodes with a short diameter >5 mm were both higher (all P<0.05). The proportion of patients with positive lymph nodes within 10 cm and the number of positive lymph nodes within 10 cm were also higher in the pPCN group (both P<0.001). Similar to the clinical TNM staging, the proportions of patients with pT3 and N2 stages, as well as the incidence of poorly differentiated tumors (G3, G4) were higher in the pPCN group ( P<0.001). The results of multivariate analysis showed that among the preoperative pathological characteristic variables, the presence of positive lymph nodes within 10 cm (OR=14.869, 95%CI: 2.993-73.858, P=0.001) and low tumor differentiation grade (OR=7.189, 95%CI: 2.091- 24.714, P=0.002) were independent risk factors for pPCN. The median follow-up time of the patients in this group was 63 (0-63) months. No local recurrence occurred in the pPCN group, and the 5-year OS was 50.0%, which was significantly lower than 78.0% in the nPCN group (HR=2.496, 95%CI: 1.263-4.930, P=0.008). The 3-year DFS was 43.8%, also significantly lower than 77.7% in the nPCN group (HR=2.950, 95%CI:1.488-5.846, P=0.002). Multivariate Cox prognostic analysis suggested that age ≥65 years (HR=2.041, 95%CI: 1.375-3.031, P<0.001), female (HR=1.838, 95%CI: 1.171-2.884, P=0.008), tumor length ≥3 cm (HR=1.747, 95%CI: 1.076-2.834, P=0.024), more advanced cT stage (HR=2.865, 95%CI: 1.234-6.653, P=0.014), and cM1 (HR=4.368, 95%CI: 2.480-7.694, P<0.001) were independent risk factors affecting OS. No neoadjuvant therapy (HR=0.636, 95%CI: 0.413-0.980, P=0.040) and cM1 (HR=5.556, 95%CI: 3.335-9.256, P<0.001) were independent risk factors affecting DFS. pPCN showed a tendency to be an independent risk factor for DFS (HR=1.942, 95%CI: 0.966-3.906, P=0.063). Conclusion:The incidence of pPCN is higher than expected, and the prognosis of patients is poor. Patients with high-risk factors may benefit from extended proximal intestinal resection (>10 cm) to avoid residual positive PCN, thereby reducing local recurrence.
6.Lateral fusion after oblique lateral lumbar interbody fusion: incidence, imaging characteristics, and contributing factors
Yongjun TONG ; Chudi FU ; Junhui LIU ; Bao HUANG ; Yilei CHEN ; Zhi SHAN ; Xuyang ZHANG ; Shunwu FAN ; Fengdong ZHAO
Chinese Journal of Orthopaedics 2025;45(7):420-428
Objective:To evaluate the characteristic manifestations of lumbar fusion following oblique lateral interbody fusion (OLIF), determine the specific incidence of these patterns, and the identify factors associated with fusion characteristics.Methods:This retrospective study analyzed 209 patients who underwent OLIF surgery at Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, between July 2017 and September 2023. The cohort had a mean age of 64.2±9.8 years and included 125 males and 84 females. A total of 338 lumbar segments were assessed, comprising 159 segments treated with stand-alone OLIF (OLIF-SA) and 179 segments treated with OLIF combined with posterior pedicle screw fixation (OLIF-PSF). Inclusion criteria were: patients aged 18-80 years who underwent OLIF with complete radiographic records. Surgical parameters, including fixation method, number of fused segments, surgical approach, and cage dimensions (height and width), were obtained from operative records. Radiographic evaluation included preoperative osteophytes, Hounsfield unit (HU) values of endplates, and cage positioning. Fusion rate, fusion pattern (lateral vs. central), cage subsidence, and related influencing factors were assessed. Clinical outcomes were measured via the Oswestry disability index (ODI) and visual analog scale (VAS) preoperatively, immediately postoperatively, and at 1-year follow-up. Results:The overall fusion rate was 98.2% (332/338), with a non-union rate of 1.8% (6/338). The incidence of lateral fusion was 40.2% (136/338). In the OLIF-SA group, lateral and central fusion rates were 50.3% (80/159) and 49.7% (79/159), respectively, with no cases of non-union. In the OLIF-PSF group, lateral fusion occurred in 31.3% (56/179), central fusion in 65.4% (117/179), and non-union in 3.3% (6/179), with statistically significant differences between groups ( P<0.05). Preoperative osteophytes and higher endplate HU values were significantly associated with lateral fusion ( P<0.05). However, cage dimensions and cage position (anterior-posterior and lateral placement) were not significantly associated with fusion pattern ( P>0.05). Overall, 61.5% (208/338) of segments showed no cage subsidence; 24.5% (83/338) had settling, and 14.0% (47/338) had grade 1 or higher subsidence. Among lateral fusion cases, the rates of no subsidence, anchoring, grade 1, grade 2, and grade 3 subsidence were 67.6%, 21.3%, 7.4%, 3.9%, and 0.7%, respectively. In the central fusion group, these rates were 59.2%, 27.6%, 9.2%, 2.5%, and 1.3%, respectively. In the non-union group, grade 2 and 3 subsidence occurred in 50% (3/6) each, significantly higher than in the other fusion groups ( P<0.05). Post hoc analysis confirmed that grade 2 and 3 subsidence rates were significantly elevated in the non-union group compared to the lateral and central fusion groups, while other subsidence categories showed no significant differences across groups. Clinically, patients showed significant improvements in ODI and VAS scores following surgery ( P<0.05). Conclusions:Lateral fusion occurred in 40.2% of OLIF cases. The OLIF-SA technique, preoperative osteophytes, and elevated preoperative HU values were significantly associated with lateral fusion. In contrast, surgical approach, number of fused segments, cage height, width, and cage positioning did not significantly influence the occurrence of lateral fusion.
7.Effect of MOTS-c on hepatocyte injury induced by glycochenodeoxycholic acid by regulating transporter MRP2 expression
Yu AO ; Xuyang ZHANG ; Dan TANG ; Gongwei LIU ; Dan HUANG ; Zhifang CAI
Organ Transplantation 2025;16(3):425-434
Objective To investigate the effects and related mechanisms of mitochondrial-derived peptide MOTS-c on glycochenodeoxycholic acid (GCDCA)-induced injury in human hepatocytes (THLE-3 cells). Methods THLE-3 cells were cultured in vitro and treated with different concentrations of GCDCA and MOTS-c. The optimal concentrations of GCDCA and MOTS-c were determined by cell counting kit (CCK)-8 method. Subsequently, THLE-3 cells were treated or pre-treated with GCDCA (200 µmol/L), MOTS-c (15, 30, 60 µmol/L), the multidrug resistance protein 2 (MRP2) inhibitor Probenecid (500 µmol/L), and the nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor ML385 (10 µmol/L). Cell proliferation was assessed by CCK-8 method. Lactate dehydrogenase (LDH) levels in the culture medium were measured by biochemical method. Cell apoptosis rates were determined by flow cytometry. MRP2 messenger RNA (mRNA) levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). MRP2 and Nrf2 protein expression levels were analyzed by Western blotting. Results As the concentration of GCDCA increased, the proliferation activity of THLE-3 cells gradually decreased, while LDH activity in the culture medium and apoptosis levels increased, and the expression levels of MRP2 in the cells decreased (all P<0.05). Treatment with 30 and 60 µmol/L MOTS-c significantly enhanced the proliferation activity of THLE-3 cells exposed to GCDCA, upregulated the expression of MRP2 and Nrf2, and reduced LDH activity and apoptosis levels (all P<0.05). Co-treatment with Probenecid partially reversed the protective effects of MOTS-c on GCDCA-induced THLE-3 cells injury, while co-treatment with ML385 partially inhibited the induction of MRP2 expression by MOTS-c in THLE-3 cells exposed to GCDCA. Conclusions MOTS-c may alleviate GCDCA-induced injury in human hepatocytes (THLE-3 cells), and its mechanism may be related to the upregulation of MRP2 expression mediated by Nrf2.
8.Polygonatum sibiricum polysaccharides may improve diabetic cardiomyopathy by inhibiting pyroptosis
Ying ZHANG ; Lulu XIE ; Zhaopeng ZHANG ; Rui GAO ; Xuyang WEI ; Meiying JIN ; Junpeng GUO
Chinese Journal of Comparative Medicine 2025;35(4):58-68
Objective To investigate the protective effect and mechanism of Polygonatum sibiricum polysaccharides(PSP)on diabetic cardiomyopathy(DCM).Methods Forty SPF-grade male Sprague-Dawley rats were divided randomly into Control,Model,PSP,and metformin groups.After 4 weeks of feeding a high-fat diet,streptozotocin was injected intraperitoneally to establish a rat model of diabetes mellitus.The drug was administered by gavage for 12 weeks,and body mass and blood glucose were recorded every 2 weeks.Cardiac function was detected by non-invasive echocardiography at week 16.Myocardial histopathological changes and the degree of myocardial fibrosis were assessed by hematoxylin and eosin and Masson staining.Serum interleukin(IL)-6,IL-1β,IL-18,tumor necrosis factor-α(TNF-α),triglycerides,total cholesterol,low-density lipoprotein,and high-density lipoprotein were detected by enzyme-linked immunosorbent assay.Expression levels of the fibrosis-related proteins transforming growth factor(TGF)-β1,Smad2,Collagen-Ⅰ,Collagen-Ⅲ,and the pyroptosis-related proteins NOD-like receptor thermal protein domain associated protein 3(NLRP3),apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),and Caspase-1 were detected in rat myocardial tissues by Western blot.Cellular experiments were performed by exposing H9c2 cells to high glucose(40 mmol/L)to mimic the in vitro DCM model,cell viability was detected by Cell Counting Kit-8 assay,and the apoptotic cell ratio was detected by flow cytometry.Results Rats in the treatment group had significantly lower blood glucose,lipid,and serum inflammatory factor levels compared with the model group(P<0.05),significantly higher ejection fraction and fractional shortening values(P<0.05),and improved cardiac function.Myocardial fibers were better aligned and collagen fiber accumulation was reduced,and myocardial tissue levels of NLRP3,ASC,Caspase-1,Collagen-Ⅰ,Collagen-Ⅲ,TGF-β1,and Smad2 were significantly reduced(P<0.05).In the cellular assay,PSP increased the viability and decreased the proportion of apoptotic cells in high glucose-induced H9c2 cardiomyocytes.Conclusions PSP can improve glucose-lipid metabolism,protect cardiac function,and delay the occurrence of myocardial fibrosis in diabetic rats,and can also improve the viability of cardiomyocytes.Its mechanism of action may be related to the inhibition of cellular pyroptosis and delayed occurrence of ventricular remodeling.
9.Development and validation of nomogram models for poor short-term response to recombinant human growth hormone treatment in children with short stature
Xuyang GONG ; Mengxing PAN ; Qianshuai LI ; Shuai ZHU ; Xinjing LIU ; Tianfang WANG ; Xulong LI ; Yanshuang CUI ; Yijing XIE ; Yi SONG ; Linlin ZHAO ; Jinqin WANG ; Yawei ZHANG ; Na XU ; Qiao REN ; Linqi DIAO ; Guijun QIN ; Yanyan ZHAO
Chinese Journal of Endocrinology and Metabolism 2025;41(6):467-475
Objective:To develop and validate clinical predictive models for identifying poor short-term response to recombinant human growth hormone(rhGH) treatment in children with short stature.Methods:A retrospective analysis was conducted on 118 children diagnosed with growth hormone deficiency or idiopathic short stature who were treated at the First Affiliated Hospital of Zhengzhou University and two other hospitals between January 1, 2020, and January 1, 2024. A poor response to rhGH was defined as a height increase of less than 0.2 standard deviation score(SDS) after 6 months of rhGH treatment. LASSO regression was used to identify predictive variables from baseline and follow-up data. Two logistic regression models were conducted: Model A(incorporating baseline variables only) and model B(incorporating both baseline and follow-up variables), and nomograms were created for visualization. External data and internal resampling were used for dual validation of the models, and their performance was compared.Results:A total of 118 children with short stature were included. Six baseline predictive variables(diagnosis, initial height SDS, bone age, bone age-chronological age difference, rhGH dose, and gender) and one follow-up variable(height SDS after 3 months of rhGH treatment) were identified. Area under the curve values for Model A and Model B were 0.753(95% CI 0.696-0.811) and 0.930(95% CI 0.891-0.975), respectively. Calibration curves, decision curve analysis, and other evaluation metrics demonstrated good discrimination and clinical utility for both models. Model B, incorporating the 3-month follow-up variable, showed superior predictive performance compared to Model A. Conclusions:The clinical prediction models developed in this study(Model A and Model B) are practical and reliable tools for quantitatively, conveniently, and intuitively identifying children with short stature at risk of poor response to rhGH treatment.
10.The role of PGC-1α mediated mitochondrial biosynthesis in the protection of AMPK agonist against hepatic ischemia-reperfusion injury
Yu Ao ; Xuyang Zhang ; Dan Tang ; Gongwei Liu ; Dan Huang ; Zhifang Cai
Acta Universitatis Medicinalis Anhui 2025;60(7):1194-1203
Objective:
To investigate the role and mechanism of PGC-1 α-mediated mitochondrial biosynthesis in AMP-activated protein kinase (AMPK) agonist anti-hepatic ischemia-reperfusion injury (HIRI) .
Methods :
SD rats were randomly divided into Control group,HIRI group,HIRI + AICAR group,HIRI + SR-18292 group and HIRI + AICAR + SR-18292 group,with 8 rats in each group.The rats were intraperitoneally injected with AICAR (500 mg / kg) or SR-18292 (32 mg / kg) before operation,and then the HIRI model was established by non-invasive vascular clamp clamping method.The samples were taken 24 hours after reperfusion.The contents of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum and the levels of malondialdehyde (MDA) ,superoxide dis- mutase (SOD) and adenosine triphosphate (ATP) in liver tissue were detected.HE staining was used to observe the pathological changes of liver tissue.The level of reactive oxygen species (ROS) and the changes of mitochondri- al membrane potential in liver tissue were detected by fluorescence probe.The copy number of mitochondrial DNA (mtDNA) and the mitochondrial biosynthesis-related genes PGC-1 α, NRF1,TFAM,UQCRC2 and other mRNA ex- pression levels were detected by qRT-PCR. Western blot was used to detect the protein expression levels of AMPKα, p-AMPKα , mTOR , p-mTOR , PGC-1α and TFAM in liver tissue.
Results :
Compared with the control group,the levels of ALT and AST in serum and MDA and ROS in liver tissue of rats in HIRI group increased,while the levels of SOD and ATP decreased ( all P <0. 05) .At the same time,the mtDNA copy number,mitochondrial membrane potential and the mRNA expression levels of PGC-1α , NRF1,TFAM,and UQCRC2 in liver tissues de- creased,and the protein ratio of p-AMPKα/AMPKα and the protein expression levels of PGC-1α and TFAM de- creased.The ratio of p-mTOR/ mTOR protein increased (both P<0. 05) .Compared with HIRI group,the levels of ALT and AST in serum and MDA and ROS in liver tissue of rats in HIRI + AICAR group decreased,while the levels of SOD and ATP increased ( all P <0. 05) .At the same time,the mtDNA copy number,mitochondrial membrane potential and the mRNA expression levels of PGC-1α , NRF1,TFAM,and UQCRC2 in liver tissue increased,and the protein ratio of p-AMPKα/AMPKα and the protein expression levels of PGC-1α and TFAM increased.The ratio of p-mTOR/ mTOR protein decreased (both P<0. 05) .However,combined with SR-18292 intervention,the protective effect of AICAR on liver tissue of HIRI rats was significantly reversed.
Conclusion
PGC-1α mediated mitochondri- al biosynthesis is involved in the regulation of AMPK agonist-mediated protective effect of HIRI,and its mechanism may be related to the activation of AMPK/ mTOR signaling pathway.


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