1.Effectiveness of TCM Health Management for Myocardial Infarction based on Tertiary Management System: A Single-arm Cohort Study of 255 Patients
Hongxin GUO ; Mingjun ZHU ; Rui YU ; Xingyuan LI ; Guangcao PENG ; Xinlu WANG ; Jianru WANG ; Bin LI ; Qifei ZHAO ; Yongxia WANG
Journal of Traditional Chinese Medicine 2024;65(8):821-829
ObjectiveTo evaluate the efficacy of TCM health management based on tertiary management system for patients with myocardial infarction (MI). MethodsA total of 277 patients with non-acute MI were enrolled and given comprehensive TCM health management strategies including health education, lifestyle adjustment, risk factors control, medication and TCM appropriate techniques management through a tertiary management system with "the patient as the core, village/community physicians as the main executive body, and tertiary TCM hospital specialists as the leading body", for a period of 12 months by using a prospective single-arm cohort study. Through patient reporting and medical records surveys, various indicators before and after 12-month management were collected and compared. The primary efficacy indicators were readmission rate and recurrent exacerbation rate, and the secondary efficacy indicators included disease awareness-related indicators, lifestyle behavior-related indicators, cardiovascular risk factor-related indicators and Canadian cardiovascular society (CCS) cardiac function classification. ResultsA total of 255 patients completed the study and were included in the final analysis. The recurrent exacerbation and readmission rates of patients after management were 23.14% (59 cases) and 20.25% (49 cases), respectively, significantly lower than 36.08% (92 cases) and 53.72% (130 cases) before management (P<0.05). Except for knowledge on diabetes diagnostic criteria with no significant difference before and after management (P>0.05), awareness of other knowledge with regard to the prevention and treatment of cardiovascular and cerebrovascular diseases were improved after management (P<0.01), as well as the total score (P<0.01). In terms of daily life behaviors, the rates of salty diet, sweet diet and greasy diet were significantly lower than baseline, while the rate of moderate exercise was significantly higher (P<0.05 or P<0.01); the rates of ongoing smoking and vigorous exercise were not significantly changed (P>0.05). For cardiovascular risk factors, patients' total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, fasting glucose, total depression assessment scale score, and total anxiety assessment scale score were significantly reduced after management (P<0.01). Systolic blood pressure and body mass index (BMI) were both higher after management (P<0.05 or P<0.01), and there was no statistically significant difference in diastolic blood pressure (P>0.05). In terms of the cardiovascular disease risk factors reaching the standard levels, the rate of LDL cholesterol <1.8 mmol/L significantly increased (P<0.01), while the rate of BMI <24 kg/m2 and the rate of systolic blood pressure <140 mmHg both decreased significantly (P<0.05 or P<0.01) from baseline; the diastolic blood pressure and rate of fasting glucose <7.0 mmol/L were not significantly changed (P>0.05). The patients' CCS cardiac function classification was significantly reduced (P<0.05). ConclusionTCM health management based on the tertiary management system can enhance MI patients' awareness of the disease, change poor lifestyle habits, reduce risk factors such as blood lipids and blood glucose, improve anxiety and depression, increase activity tolerance, and reduce their recurrence exacerbation and readmission rates, which is worthy of clinical promotion.
2.Efficacy of concurrent tumor treating fields and chemoradiation in patients with high-grade glioblastoma
Zixuan WANG ; Dan ZONG ; Huanfeng ZHU ; Xiao WANG ; Mingjun DING ; Wenjie GUO ; Jiajun ZHENG ; Xia HE
Chinese Journal of Radiation Oncology 2024;33(4):307-313
Objective:To evaluate the safety and efficacy of tumor-treating fields (TTFields) and chemoradiation in patients with high-grade glioblastoma.Methods:Clinical data of 38 patients admitted to the Jiangsu Cancer Hospital from September 2021 to May 2023 who were diagnosed with high-grade glioblastoma (36 cases of World Health Organization grade Ⅳ and 2 cases of grade Ⅲ) were retrospectively analyzed. All patients received TTFields combined with concurrent chemoradiation after surgery. Response assessment in neuro-oncology (RANO) criteria was used to evaluate the glioma responses as tumor remission, stable or progression. Common terminology criteria for adverse events v5.0 and TTFields related skin adverse reaction (dAE) criteria were used to evaluate the adverse events. Treatment compliance was assessed by data on the NovoTTF-200A therapeutic device, calculated as a percentage of daily TTFields usage time. Survival analysis was estimated by the Kaplan-Meier method and compared by the log-rank test.Results:The median duration of treatment with TTFields in 38 patients was 20 h (rang: 2.4-22.6 h), and the median treatment compliance was 83% (range: 10%-94%). After 42 days of TTFields combined with concurrent chemoradiation, 12 patients who underwent complete tumor resection were assessed as stable according to RANO criteria. Among the 26 patients who underwent partial tumor resection, 23 (88%) were evaluated as disease remission according to RANO criteria. The 7-, 10-, 13-month progression-free survival rate was 81.0%、64.0%、49.5%, repectively. The common adverse events included grade 1 (45%) and grade 2 (8%) dAE, without grade 3-4 dAE. Typical presentations included contact dermatitis, blisters, lesions or ulcers, and abscesses. The median follow-up time was 10.0 months (range: 1.6-21.3 months). At follow-up as of July 2023, 26 of the 38 patients were stable and 12 had disease progression (8 died).Conclusion:The preliminary results show that TTFields combined with chemoradiation is effective, safe and reliable treatment for high-grade glioblastoma.
3.Screening and experimental validation of hub genes for myocardial isch-emia-reperfusion injury based on bioinformatics
Jianru WANG ; Xingyuan LI ; Shiyang XIE ; Yanling CHENG ; Hongxin GUO ; Mingjun ZHU ; Rui YU
Chinese Journal of Pathophysiology 2024;40(3):473-483
AIM:Using bioinformatics analysis methods to identify the hub genes involved in myocardial isch-emia-reperfusion injury(MIRI).METHODS:Firstly,the rat MIRI related dataset GSE122020,E-MEXP-2098,and E-GEOD-4105 were downloaded from the database.Secondly,differentially expressed genes(DEGs)were screened from each dataset using the linear models for microarray data(limma)package,and robust DEGs were filtered using the robust rank aggregation(RRA)method.In addition,the surrogate variable analysis(SVA)package was used to merge all datas-ets into one,and merged DEGs were screened using the limma package.The common DEGs were obtained by taking the intersection of the two channels of DEGs.Next,the protein-protein interaction(PPI)network of common DEGs was con-structed,and the hub genes were identified using the density-maximizing neighborhood component(DMNC)algorithm.The receiver operating characteristic curve(ROC)was plotted to evaluate the diagnostic performance of the hub gene.Then,the mRNA and protein expression levels of hub genes were detected in the rat MIRI model,and the literature re-view analysis was carried out on the involvement of hub genes in MIRI.Finally,the gene set enrichment analysis(GSEA)was performed on hub gene to further reveal the possible mechanism in mediating MIRI.RESULTS:A total of 143 robust DEGs and 48 merged DEGs were identified.After taking the intersection of the two,48 common DEGs were obtained.In the PPI network of common DEGs,5 hub genes were screened out,namely MYC proto-oncogene bHLH transcription fac-tor(MYC),prostaglandin-endoperoxide synthase 2(PTGS2),heme oxygenase 1(HMOX1),caspase-3(CASP3),and plasminogen activator urokinase receptor(PLAUR).The ROC results showed that the area under the curve values for all hub genes were greater than 0.8.MYC,PTGS2,CASP3,and PLAUR showed high mRNA and protein expression in rat MIRI,while there was no difference in mRNA and protein expression for HMOX1.The literature review revealed that among the 5 hub genes,only PLAUR has not been reported to be involved in MIRI.The GSEA results for PLAUR indicat-ed that its functional enrichment mainly focused on pathways such as NOD-like receptor signaling pathway,P53 signaling pathway,Toll-like receptor signaling pathway,apoptosis,and fatty acid metabolism.CONCLUSION:MYC,PTGS2,CASP3,HMOX1,and PLAUR are involved in the pathological process of MIRI.PLAUR is a potential hub gene that can mediate MIRI by regulating pathways such as NOD like receptor signaling,P53 signaling,Toll like receptor signaling,cell apoptosis,and fatty acid metabolism.The results can provide reference for further investigation into the molecular mechanisms and therapeutic targets of MIRI.
4.A Cross-Sectional Study of Secondary Prevention Status and Influencing Factors of Stable Angina in 1061 Patients with Coronary Heart Disease
Rui YU ; Yingqiang ZHAO ; Peng LI ; Jianru WANG ; Xinlu WANG ; Qifei ZHAO ; Yuan GAO ; Hongxin GUO ; Mingjun ZHU
Journal of Traditional Chinese Medicine 2024;65(20):2126-2134
ObjectiveTo investigate the current status of secondary prevention of stable angina in patients with coronary heart disease in three regions of China, namely Henan Province, Xinjiang Uygur Autonomous Region, and Tianjin City, and analyze the the influencing factors. MethodsA cross-sectional study was conducted to include patients with stable angina with coronary heart disease in Henan, Tianjin and Xinjiang from August 10, 2020 to March 14, 2021. General information, traditional Chinese medicine (TCM) syndrome elements, prescriptions and other data of patients were collected, and clinical characteristics, blood pressure, blood lipid and blood glucose of patients were analyzed; the patients were divided into groups according to whether their blood pressure, blood lipid and blood glucose were up to standard. With the most common syndrome element as the main variable, region, age and gender as covariables, Logistic regression equation was incorporated to analyze the influencing factors for the patients' blood pressure, blood lipid and blood glucose being up to standard. ResultsA total of 1061 coronary heart disease patients with stable angina were included, including 658 in Henan, 210 in Xinjiang, and 193 in Tianjin. The clinical characteristics of patients in the three regions showed statistical different in age, sex, disease course, complication, blood pressure, blood lipid, blood glucose, smoking, drinking, living habits, and medication treatment (P<0.05 or P<0.01). For the included patients, qi deficiency (79.55%, 844/1061) and blood stasis (39.96%, 424/1061) were the main syndrome elements. The overall compliance rate of blood pressure was 48.89% (506/1035), blood lipids 12.68% (133/1049) and blood glucose 48.18% (504/1046). Qi deficiency was the independent factor affecting the blood pressure of coronary heart disease patients with stable angina combined with hypertension (P = 0.029,95%CI [1.048, 2.369]), and the independent factors influencing the blood lipid standard of coronary heart disease patients with stable angina (P = 0.011, 95%CI [1.133, 2.646]), but not the independent factors affecting blood glucose standard in coronary heart disease patients with diabetes (P>0.05). ConclusionCoronary artery disease patients with stable angina have geographical variability in clinical characteristics and distribution of TCM syndrome elements, and the overall control of blood pressure, blood lipids, and blood glucose is poor, and qi deficiency syndrome is an independent risk factor affecting the control of blood pressure and blood lipids.
5.Exploration on "Symptom-Syndrome-Drug" Regularity of Traditional Chinese Medicine for Coronary Microvascular Disease Based on Latent Structure Combined with Association Rules
Yilin ZHANG ; Jingjing WEI ; Hongxin GUO ; Lele HUO ; Mingjie ZHANG ; Jianfeng LU ; Aolong WANG ; Mingjun ZHU
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(5):730-740
Objective To systematically explore the traditional Chinese medicine(TCM)common symptoms,syndrome elements,clinical syndrome differentiation,and medication rules of coronary microvascular disease(CMVD),and to provide a reference for quantitative criteria of clinical differentiation of CMVD,specification of the diagnosis and efficacy evaluation of TCM clinical syndrome,and guidance of clinical medication.Methods The databases including CNKI,Wanfang,VIP,and SinoMed were searched for research papers on the treatment of CMVD by TCM published from database inception to May 16,2023.Relevant information of the included literature was extracted and the database was established.Then,the frequency statistics of symptoms,syndrome elements,syndrome types and Chinese medicinals were carried out.Latent structural models were constructed using Latern 5.0 and Rstudio softwares respectively for comprehensive clustering and association rule analysis,so as to explore the symptom characteristics,syndrome elements distribution,common syndromes and medication rules for TCM treatment of CMVD.Results A total of 107 literature were included,involving 36 syndromes,17 syndrome elements,121 symptoms and 143 Chinese medicinals.It was speculated that the main syndrome element of CMVD was blood stasis,followed by qi deficiency,qi stagnation,phlegm turbidity,yin deficiency and yang deficiency.The main type of syndrome was qi deficiency and blood stasis,followed by heart blood stasis obstruction,qi stagnation and blood stasis,phlegm blended with stasis,qi-yin deficiency,etc..The main medicinals were Chuanxiong Rhizoma,Salviae Miltiorrhizae Radix et Rhizoma,Angelica Sinensis Radix and Astragali Radix.The medicinals used in the treatment of CMVD were classified as blood-activating and stasis-resolving drugs,deficiency-tonifying drugs,qi-regulating drugs in terms of their efficacy.Conclusion The location of CMVD is in heart,and related to liver and kidney.The syndrome of CMVD is deficiency in origin and excess in superficiality.Blood stasis runs through the development of the disease.The treatment is mainly to activate blood circulation and remove stasis,activate meridians and relieve pain,which should be supplemented with the therapies of tonifying and invigorating qi,soothing the liver and regulating qi,dispelling phlegm and dissipating masses according to the patients'syndromes.
6.Efficacy and safety of Tofacitinib in treating the elderly rheumatoid arthritis
Keqin ZENG ; Erye ZHOU ; Tian REN ; Yufeng YIN ; Michun HE ; Xianming LONG ; Mingjun WANG ; Yufan GUO ; Jian WU
Chinese Journal of Geriatrics 2023;42(1):40-45
Objective:To observe the efficacy and safety of Tofacitinib in treating elderly rheumatoid arthritis(RA), in order to provide clinical evidence.Methods:In the randomized control trial, a total of 90 elderly RA patients admitted to the Department of Rheumatology of the First Affiliated Hospital of Soochow University from January 2019 to January 2021 were selected and divided into Methotrexate group(MTX group, MTX 10mg, qw, n=45)and Tofacitinib group(TOF group, oral 5mg, bid, n=45). The efficacy and safety of the two groups were evaluated at week 12.The primary endpoint was the proportion of patients meeting the American College of Rheumatology 50%(ACR50)improvement response criteria at week 12.Secondary endpoints included ACR20/70 improvement response, proportion of patients who met treat-to-target(T2T)criteria, including Disease Activity Score in 28 joints using erythrocyte sedimentation rate(DAS28-ESR), Disease Activity Score in 28 joints using C-reactive protein level(DAS28-CRP), clinical disease activity index(CDAI), and simplified disease activity index(SDAI), and patient-reported outcomes(PROs)which included changes compared to baseline in pain visual analog scale(VAS)and Health Assessment Questionnaire Disability Index(HAQ-DI)score, at week 12.Safety outcomes including drug-related adverse events, serious adverse events, dropping out due to adverse events, and deaths were assessed throughout.Results:Five patients in each group withdrew from the trial due to adverse events, and the number of patients who finally completed the observation was 40 in each group.At week 12, the ACR50 response rate was higher in TOF group than in MTX group[35%(14/40) vs.12.5%(5/40), χ2=5.591, P=0.018)], achieving the primary endpoint.When comparing TOF vs.MTX group, the ACR20 response rate[55%(22/40) vs.25%(10/40), χ2=7.500, P=0.006]and ACR70 response rate[25%(10/40) vs.7.5%(3/40), χ2=4.501, P=0.034], and proportions of indexes of disease remission including DAS28-ESR<2.6[25%(11/40) vs.7.5%(3/40), χ2=4.501, P=0.034], or DAS28-CRP<2.6[27.5%(11/40) vs.7.5%(3/40), χ2=5.541, P=0.019], or CDAI≤2.8[30%(12/40) vs.10%(4/40), χ2=5.000, P=0.025], or SDAI≤3.3[27.5%(11/40) vs.7.5%(3/40), χ2=5.541, P=0.019], and the proportions of patients with low disease activity including DAS28-ESR≤3.2[32.5%(14/40) vs.12.5%(5/40), χ2=5.591, P=0.018], or DAS28-CRP≤3.2[32.5%(14/40) vs.12.5%(5/40), χ2=5.591, P=0.018], or CDAI≤10[37.5%(15/40) vs.17.5%(7/40), χ2=4.013, P=0.045], or SDAI≤11[37.5%(15/40) vs.15%(6/40), χ2=5.230, P=0.022], as well as changes compared to baseline data in pain VAS[(26.51±8.32)scores vs.(14.16±4.39)scores, t=8.371, P<0.001]and in HAQ-DI score(0.65±0.24 vs.0.32±0.06, t=9.387, P<0.001)were all better in the TOF group than in the MTX group at week 12.During the 12-week observation period, the number of patients with infection and hyperlipidemia was higher in TOF group than in MTX group, while the number of patients with abnormal blood cell count and liver function was lower than that in MTX group, but the differences were not statistically significant(all P<0.05). Conclusions:Tofacitinib has good efficacy and safety in the elderly RA.In patients over 70 years of age who are at high risk of infection, tofacitinib should be used with caution.
7.Anatomy of the perforator propeller flap of superior lateral genicular artery and its clinical application in repair of soft tissue defect of anterolateral knee
Zhenhua XU ; Zhaohui YE ; Weiwei CHEN ; Mingjun GUO ; Peng WEI
Chinese Journal of Microsurgery 2023;46(1):89-94
Objective:To study the anatomy of the perforator propeller flap of superior lateral genicular artery, and to explore a surgical method and clinical application in repair of the soft tissue defect of anterolateral knee with the flap.Methods:From September 2019 to September 2021, 8 knees of 4 chilled fresh specimen of adults were studied. The perforators of the superior lateral genicular artery were observed. The length, outer diameter of the perforators, and the locations of the skin perforation were recorded. The superior lateral genicular artery perforator propeller flaps were then applied clinically to 5 patients(3 males and 2 females) with soft tissue defects of anterolateral knee. Two of the patients had combined ligament injury and(or) bone joint exposure. The age of patients ranged from 25 to 48 years old, at 33.4 years old in average. The sizes of soft tissue defects ranged from 4.0 cm×4.0 cm to 8.0 cm×5.0 cm. The sizes of perforator propeller flaps of superior lateral genicular artery were 10.0 cm×5.0 cm to 13.0 cm×6.0 cm. The superior perforating vessels of the superior lateral genicular artery were found and marked at the points of skin perforation. Preoperative contrast-enhanced ultrasound were performed to confirm the dominant perforating vessels and had the skin perforating points marked. Intraoperative CDU were further performed to confirm the points of dominant perforating vessels. Perforator propeller flaps were designed depending on the size of the anterolateral soft tissue defect, and flaps were prepared and transferred to the defect sites. Postoperative follow-ups were conducted at outpatient clinic. The survival of the flap and knee function were observed according to the Bai-ly knee scoring.Results:The anatomy showed that an average pedicle length of the superior lateral genicular artery perforator was(8.2±0.9) cm, with an average starting outer diameter at(1.1±0.2) mm. All 5 flaps survived during the follow-up that lasted for 10 to 24 months, with an average of 15.3 months. All flaps healed in 2 weeks after surgery without complications such as soft tissue infection, bone and joint infection were observed. At the last follow-up, no obvious bloated appearance of the flaps were observed. The colour and elasticity of the flaps were similar to the surrounding skin. The knee function was assessed: 4 patients were in excellent and 1 in good. The range of knee flexion and extension was from 100° to 150°. The patients were satisfied with the appearance and function of the knees.Conclusion:The size of the perforator of superior lateral genicular artery and the pedicle length are ideal. The propeller flap can be used to repair the soft tissue defect around the anterolateral knee, with satisfactory functional recovery of a knee. It is a good method to repair the soft tissue defect around anterolateral knee.
8.Epidemiological characteristics of SARS-CoV-2 pneumonia in kidney transplant recipients : a single-center retrospective study
Fen WEI ; Ning LI ; Mingjun WANG ; Xiaohong GUO
Organ Transplantation 2023;14(5):700-707
Objective To investigate the epidemiological characteristics of SARS-CoV-2 pneumonia in kidney transplant recipients and analyze the risk and protective factors of severe/critical infection with SARS-CoV-2. Methods Clinical data of 468 kidney transplant recipients infected with SARS-CoV-2 were retrospectively analyzed. According to the severity of infection, they were divided into mild SARS-CoV-2 infection recipients (n=439) and SARS-CoV-2 pneumonia group (n=29). Among the 439 mild SARS-CoV-2 infection recipients, 87 recipients who were randomly matched with their counterparts in the SARS-CoV-2 pneumonia group according to sex, age and transplantation time at a ratio of 3∶1 were allocated into the mild SARS-CoV-2 infection group. Twenty-nine recipients in the SARS-CoV-2 pneumonia group were divided into the moderate SARS-CoV-2 pneumonia group (n=21) and severe/critical SARS-CoV-2 pneumonia group (n=8). Baseline data of all recipients were collected. The risk and protective factors of SARS-CoV-2 infection in kidney transplant recipients were identified. Results The proportion of recipients complicated with 2-3 types of complications in the SARS-CoV-2 pneumonia group was higher than that in the mild SARS-CoV-2 infection group, and the proportion of recipients treated with tacrolimus(Tac)+mizoribine+glucocorticoid immunosuppression regimen in the SARS-CoV-2 pneumonia group was lower than that in the mild SARS-CoV-2 infection group, and significant differences were observed (both P<0.05). In 29 kidney transplant recipients with SARS-CoV-2 pneumonia in the SARS-CoV-2 pneumonia group, white blood cells, the absolute values of lymphocytes, eosinophils, total T cells, CD4+T cells and CD8+T cells, and serum uric acid levels were significantly lower, whereas ferritin levels were significantly higher than the values prior to SARS-CoV-2 pneumonia, and significant differences were observed (all P<0.05). Compared with the moderate SARS-CoV-2 pneumonia group, the proportion of recipients with hypoxemia was higher, the proportion of recipients treated with Tac/ciclosporin (CsA)+mycophenolate mofetil+glucocorticoid immunosuppression regimen was higher, and the proportion of recipients administered with 2-3 doses of SARS-CoV-2 vaccine was lower in the severe/critical SARS-CoV-2 pneumonia group, and significant differences were observed (all P<0.05). Conclusions More complications and immunosuppression regimen containing mycophenolate mofetil are the risk factor for SARS-CoV-2 infection in kidney transplant recipients. Vaccination with SARS-CoV-2 vaccine and immunosuppression regimen containing mizoribine are probably the protective factors for lowering the risk of SARS-CoV-2 infection. The levels of inflammatory cytokines are associated with the severity of SARS-CoV-2 pneumonia.
9.A Data Mining-Based Study on the Medication Rules of Chinese Medicine to Treat Heart Failure with Diuretic Resistance
Hongxin GUO ; Bin LI ; Haifeng YAN ; Xingyuan LI ; Mingjun ZHU
World Science and Technology-Modernization of Traditional Chinese Medicine 2023;25(9):3063-3070
Objective To explore the medication rules of clinical prescriptions of Chinese medicine in the treatment of heart failure with diuretic resistance based on data mining method.Methods Seven domestic and foreign databases,including CNKI and Wanfang,were searched for literature on Chinese medicine for heart failure with diuretic resistance from the establishment of the database to October 2021.Frequency analysis,association rule analysis and cluster analysis were used for statistical analysis.Results A total of 41 literatures were included,including 39 prescriptions.Yang deficiency and water retention were the main symptoms of the disease.A total of 72 single herbs were used,with a total of 438 times of use.There are 30 Chinese medicines with a frequency of more than 5 times,involving 9 efficacy categories,mainly tonic medicines,diuresis and dampness medicines,blood-activating and stasis-removing medicines,and interior-warming medicines.The association rule analysis yielded drug compatibility with Poria as the core,such as Atractylodis Macrocephalae Rhizoma→Poria and Cinnamomi Ramulus→Poria.Cluster analysis yielded six new formula combinations with efficacy in warming Yang,inducing diuresis,benefiting qi and invigorating Blood.Conclusion Heart failure with diuretic resistance is a syndrome of root vacuity and tip repletion,cold-heat complex,and the core pathogenesis is"deficiency","water"and"stasis".The treatment of this disease occurs by warming yang and excreting water,supplemented by replenishing qi and activating blood circulation.Poria with Atractylodis Macrocephalae Rhizoma and Cinnamomi Ramulus are commonly used combinations,and Zhen Wu Decoction is the basic formula for the treatment of this disease.
10. Role and mechanism of SIRT3 in attenuation of intestinal ischemia-reperfusion injury by dexmedetomidine in mice
Yixing REN ; Yufang LENG ; Mingjun GUO ; Jianmin ZHANG ; Yajing SHI ; Feng CHEN ; Xin LIU ; Yixing REN
Chinese Journal of Clinical Pharmacology and Therapeutics 2022;27(3):253-259
AIM: To explore the role and mechanism of silent mating type information regulator 2 homolog 3 (SIRT3) in attenuation of intestinal ischemia-reperfusion (I/R) injury by dexmedetomidine in mice. METHODS: Twenty-four healthy male C57BL mice were divided into 4 groups randomly (n=6): sham operation group (Sham group), intestinal ischemia-reperfusion group (I/R group), dexmedetomidine group (Dex group), SIRT3 inhibitor 3-TYP group (3-TYP group). Superior mesenteric artery was clamped for 45 min followed by reperfusion for 2 h to establish intestinal I/R model in I/R group, Dex group, and 3-TYP group. Sham group received sole sham operation. 1 h prior to onset of ischemia, 3-TYP was injected into mice in 3-TYP group intraperitoneally (5 mg/kg, diluted to 0.3 mL), and 0.3 mL normal saline into mice in Dex group intraperitoneally. 30 min prior to onset of ischemia, dexmedetomidine was injected into mice in 3-TYP group and Dex group intraperitoneally (25 μg/kg, diluted to 0.3 mL). 1 h and 30 min prior to onset of ischemia, 0.3 mL normal saline was injected into mice in Sham group and I/R group intraperitoneally, respectively. 2 h of after reperfusion, the mice were sacrificed under anesthesia. Intestinal tissues were took and observed for pathological changes under light microscope after HE staining, and the injury was assessed via the Chiu's score method, and activities of SIRT3 and superoxide dismutase 2 (SOD2) were detected via spectrophotometry, and malondialdehyde (MDA) via spectrophotometry. RESULTS: The pathological injury was exacerbated, and the Chiu's score, the MDA level elevated remarkably, while the activity level of SIRT3 and SOD2 declined remarkably in I/R group, Dex group and 3-TYP group compared to Sham group (P<0.05). The pathological injury was alleviated, and the Chiu's score declined remarkably in Dex group and 3-TYP group compared to I/R group (P<0.05); and the MDA level declined remarkably, while activity level of SIRT3 and SOD2 elevated remarkably in Dex group compared to I/R group (P<0.05); and there was no significant difference both in the activity level of SIRT3 and SOD2 and in the MDA level between 3-TYP group and I/R group. The pathological injury was exacerbated, and the Chiu's score, the MDA level elevated remarkably, while the activity level of SIRT3 and SOD2 declined remarkably in 3-TYP group compared to Dex group (P<0.05). CONCLUSION: SIRT3 and its downstream SOD2 are involved in mediating the effect of attenuation of intestinal ischemia-reperfusion injury through inhibiting oxidative stress response by dexmedetomidine.

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