1.Baicalin alleviates lipopolysaccharide-induced myocardial cell injury by down-regulating miR-221 and its mechanism
Yijing JIN ; Kandong LI ; Zhihui ZHAN ; Yong WANG
Chinese Journal of Immunology 2025;41(7):1688-1694
Objective:To explore the effects of microRNA-221(miR-221)on inflammation and fibrosis induced by lipopoly-saccharide(LPS)in rat cardiomyocytes and the regulatory role of phosphatidylinositol 3-kinase(PI3K)/seronine/threonine protein kinase(AKT)signaling pathway.Methods:Cultured rat myocardial H9C2 cells in vitro,they were divided into control group(no inter-vention),LPS group(10 μg/ml LPS),experimental group(10 μg/ml LPS+10,20,40,80 μmol/L baicalin),mimics NC group(10 μg/ml LPS+mimics NC transfection),miR-221 mimics group(10 μg/ml LPS+transfection miR-221 mimics),inhibitor NC group(10 μg/ml LPS+transfection inhibitor NC),miR-221 inhibitor group(10 μg/ml LPS+transfection miR-221 inhibitor),10+miR-221 mimics group(10 μg/ml LPS+10 μmol/L baicalin+transfection miR-221 mimics)and 10+miR-221 inhibitor group(10 μg/ml LPS+10 μmol/L baicalin+transfection miR-221 inhibitor)were treated for 24 h.Real-time quantitative fluorescence PCR(RT-qPCR),ELISA,CCK-8,5-acetyne-2'-deoxyuracil nucleoside(EdU)and Transwell chamber methods were used to determine the expression level of miR-221,the expression levels of inflammatory factors,cell viability,cell proliferation and migration ability,Western blot was used to determine the expression levels of EMT-related proteins[E-cadherin,N-cadherin,Vimentin,fibronectin(FN)]and PI3K/AKT pathway related proteins.Results:Cell viability increased in LPS+10 group(P<0.05),so LPS+10 group was selected for follow-up experiment.The results of miR-221 level showed that miR-221 mimics group was higher than mimics NC group(P<0.05),miR-221 inhibitor group was lower than inhibitor NC group(P<0.05).Transfection of miR-221mimics group and miR-221 inhibitor group was successful.Compared with control group,cell proliferation rate and E-cadherin protein level in LPS group were decreased(P<0.05).The expression level of miR-221,cell migration number,IL-6 and TNF-α levels,and the protein levels of p-PI3K,p-AKT,N-cadherin,FN and Vimentin were increased(P<0.05).Compared with LPS group,LPS+10 group significantly reversed the changes of the above indexes(P<0.05).Compared with LPS+10 group,10+miR-221 mimics group reduced the above effect of baicalin in LPS-induced cells(P<0.05).However,miR-221 inhibitor of 10+miR-221 inhibitor group enhanced the above effect of baicalin in LPS-induced cells(P<0.05).Conclusion:Baicalin can inhibit the effects of LPS-induced myocyte H9C2 migration,inflammation and fibrosis and promote their proliferation by down-regulating the expression of miR-221,and its mechanism may be related to the inhibi-tion of PI3K/AKT signaling pathway.
2.Baicalin alleviates lipopolysaccharide-induced myocardial cell injury by down-regulating miR-221 and its mechanism
Yijing JIN ; Kandong LI ; Zhihui ZHAN ; Yong WANG
Chinese Journal of Immunology 2025;41(7):1688-1694
Objective:To explore the effects of microRNA-221(miR-221)on inflammation and fibrosis induced by lipopoly-saccharide(LPS)in rat cardiomyocytes and the regulatory role of phosphatidylinositol 3-kinase(PI3K)/seronine/threonine protein kinase(AKT)signaling pathway.Methods:Cultured rat myocardial H9C2 cells in vitro,they were divided into control group(no inter-vention),LPS group(10 μg/ml LPS),experimental group(10 μg/ml LPS+10,20,40,80 μmol/L baicalin),mimics NC group(10 μg/ml LPS+mimics NC transfection),miR-221 mimics group(10 μg/ml LPS+transfection miR-221 mimics),inhibitor NC group(10 μg/ml LPS+transfection inhibitor NC),miR-221 inhibitor group(10 μg/ml LPS+transfection miR-221 inhibitor),10+miR-221 mimics group(10 μg/ml LPS+10 μmol/L baicalin+transfection miR-221 mimics)and 10+miR-221 inhibitor group(10 μg/ml LPS+10 μmol/L baicalin+transfection miR-221 inhibitor)were treated for 24 h.Real-time quantitative fluorescence PCR(RT-qPCR),ELISA,CCK-8,5-acetyne-2'-deoxyuracil nucleoside(EdU)and Transwell chamber methods were used to determine the expression level of miR-221,the expression levels of inflammatory factors,cell viability,cell proliferation and migration ability,Western blot was used to determine the expression levels of EMT-related proteins[E-cadherin,N-cadherin,Vimentin,fibronectin(FN)]and PI3K/AKT pathway related proteins.Results:Cell viability increased in LPS+10 group(P<0.05),so LPS+10 group was selected for follow-up experiment.The results of miR-221 level showed that miR-221 mimics group was higher than mimics NC group(P<0.05),miR-221 inhibitor group was lower than inhibitor NC group(P<0.05).Transfection of miR-221mimics group and miR-221 inhibitor group was successful.Compared with control group,cell proliferation rate and E-cadherin protein level in LPS group were decreased(P<0.05).The expression level of miR-221,cell migration number,IL-6 and TNF-α levels,and the protein levels of p-PI3K,p-AKT,N-cadherin,FN and Vimentin were increased(P<0.05).Compared with LPS group,LPS+10 group significantly reversed the changes of the above indexes(P<0.05).Compared with LPS+10 group,10+miR-221 mimics group reduced the above effect of baicalin in LPS-induced cells(P<0.05).However,miR-221 inhibitor of 10+miR-221 inhibitor group enhanced the above effect of baicalin in LPS-induced cells(P<0.05).Conclusion:Baicalin can inhibit the effects of LPS-induced myocyte H9C2 migration,inflammation and fibrosis and promote their proliferation by down-regulating the expression of miR-221,and its mechanism may be related to the inhibi-tion of PI3K/AKT signaling pathway.
3.Epidemiological characteristics of hemorrhagic fever with renal syndrome in Hu'nan Province from 2018 to 2023
CHEN Shengbao ; DAI Zhihui ; ZHAN Zhifei
China Tropical Medicine 2024;24(11):1400-
Objective To analyze the epidemiological characteristics of hemorrhagic fever with renal syndrome (HFRS) in Hu'nan Province from 2018 to 2023, providing a scientific basis for formulating prevention and control measures in the future. Methods Descriptive epidemiological methods were used to describe the temporal, spatial, and population distributions of HFRS cases in Hunan Province. Host animal density between indoor and outdoor, host animal density, and virus-carrying status across different years were compared using the Chi-square test. Spearman correlation analysis was used to assess the relationship between human HFRS incidence and host animal rodent density and specimen positivity rate. Results A total of 3 079 cases of HFRS were reported in Hunan Province from 2018 to 2023, with 10 deaths. The average annual incidence rate was 0.75/100 000, and the average annual mortality rate was 0.0024/100 000. HFRS cases showed a bimodal distribution of spring and winter peaks, with cases reported during these peaks accounting for 67.39% of the total cases over six years. The cases were mainly concentrated in Changsha City, Changde City, and Yiyang City. In terms of population distribution, the male-to-female ratio was 2.37∶1, with cases predominantly occurring in the middle-aged and elderly populations, with cases over 40 years old accounting for 79.44% of the total number of cases. Farmers were the primary occupational group affected. The average rodent density in Hunan Province from 2018 to 2023 was 2.88%, with indoor rat density higher than outdoor density. There were statistically significant differences in rat density across different years (χ2=21.301, P<0.01), in the positivity rate of host animals across different years (χ2=22.307, P<0.01), and in the composition of positive rat species and virus subtypes across different habitats (χ2=70.653, 10.627, P<0.01). There was a correlation between the human HFRS incidence and the positivity rate of host animal specimens (r=0.39, P<0.05). Conclusions In recent years, the overall incidence rate of HFRS in Hunan Province has shown an overall downward trend, with seasonal peaks and a higher risk of incidence among farmers. In the future, continuous monitoring should be strengthened, and patriotic health campaigns such as rodent control should be organized before the peak seasons to reduce the risk of disease transmission.
4.The efficacy of immunosuppression combined with Eltrombopag in the treatment of severe aplastic anemia in children
Yanping ZHANG ; Mengmeng LIU ; Xinrong ZHAN ; Pengtao XING ; Zhihui LI ; Zhongliang WANG
Chinese Journal of Applied Clinical Pediatrics 2022;37(5):348-351
Objective:To explore the efficacy and clinical significance of Eltrombopag combined with immunosuppression therapy(IST) in the treatment of severe aplastic anemia (SAA) in children.Methods:Clinical data of 63 children with initially diagnosed SAA in the Department of Hematology of Xinxiang Central Hospital from May 2017 to June 2019 were retrospectively analyzed.All of them were all donors without siblings and they were classified into observation group (31 cases) and control group (32 cases). Patients in the observation group received IST combined with Eltrombopag treatment, and those in the control group received IST treatment.The Chi- square test was used to compare the overall remission (OR) rate and complete remission (CR) rate at 3 months, 6 months and 12 months, and incidence of infection and significant bleeding between groups.The t-test was used to compare the application of gra-nulocyte colony stimulating factor, the mean red blood cell transfusion, and the mean platelet infusion volume between groups.Kaplan-Meier method was adopted to analyze the 2-year overall survival (OS) rate and failure-free survival (FFS) rate, followed by the Log- rank test. Results:The 3-month and 6-month OR rate of the observation group were 61.29%(19/31 cases) and 80.64% (25/31 cases), respectively, which was significantly higher than that of the control group [37.50%(12/32 cases) and 59.38%(19/32 cases), χ2=45.27, 43.81, respectively, all P<0.05]. The 3-month and 6-month CR rate of the observation group were 32.26%(10/31 cases) and 45.16%(14 /31 cases), respectively, which was significantly higher than that of the control group [15.62%(5/32 cases) and 28.13%(9/32 cases), χ2=47.02, 48.35, respectively, all P<0.05]. The 12-month OR rate and CR rate in the observation group were 83.87%(26/31 cases), and 64.52%(20/31 cases), respectively, which were 81.25%(26/32 cases), and 59.38%(19/32 cases), respectively in the control group, and no significant differences in them were detected between the two groups (all P>0.05). The total amount of granulocyte colony stimulating factors [(13.58±4.28) doses vs.(23.24±6.68) doses, t=2.591], and the mean infusion volume of red blood cells [(5.48±1.67) U vs.(10.58±3.67) U, t=2.040] and platelets (4.15±2.47) bags vs.(9.15±3.87) bags, t=2.744) used in observation group within 6 months of treatment were significantly lower than those of the control group (all P<0.05). The rate of infection (16.13% vs.43.75%, χ2=47.12) and significant bleeding (16.13% vs.37.50%, χ2=44.52) in the observation group were significantly lower than those of the control group (all P<0.05). The 2-year OS rate of the observation group and control group were 93.55% (29/31 cases), and 87.50% (28/32 cases), respectively.No significant difference in the OS rate was found between groups ( P=0.407 3), nor as the 2-year FFS rate(87.10% vs.78.13%, P=0.326 6). Conclusions:IST combined with Eltrombopag can significantly improve the early treatment response rate of SAA children without a sibling identical donor, which can reduce red blood cell and platelet transfusion, and the incidence of infection and bleeding.
5.Incidence and prognoses of human cytomegalovirus reactivation in immunocompetent severe pneumonia patients with mechanical ventilation
Zhihui ZHANG ; Xuesong LIU ; Sibei CHEN ; Zhan WU ; Yining SUN ; Ling SANG ; Yonghao XU ; Weiqun HE ; Yimin LI ; Xiaoqing LIU
Chinese Critical Care Medicine 2021;33(3):286-292
Objective:To investigate the incidence and risk factors of human cytomegalovirus (HCMV) reactivation in immunocompetent severe pneumonia patients with mechanical ventilation and their effects on clinical outcomes.Methods:A prospective observational study was conducted. Forty-eight immunocompetent patients requiring invasive mechanical ventilation due to severe pneumonia in the department of critical care medicine of the First Affiliated Hospital of Guangzhou Medical University from June 30th, 2017 to July 1st, 2018 were enrolled. Meanwhile, all cases were followed up until 90 days after inclusion and were required to quantitatively detect HCMV DNA in serum at regular weekly intervals until 28 days after transferring to intensive care unit (ICU). Patients were divided into HCMV reactivation group (≥5×10 5 copies/L) and non-reactivation group (<5×10 5 copies/L) based on HCMV DNA at any time point within 28 days. Demographic data, basic indicators, respiratory indicators, disease severity scores, laboratory indicators, complication and clinical outcomes of the two groups were collected and analyzed. Multivariate Logistic regression analysis was performed to screen independent risk factors for HCMV reactivation. Results:All 48 subjects were tested positive for HCMV immunoglobulin G (IgG), so HCMV seropositive rate was 100%. HCMV reactivation occurred in 10 patients within 28 days after admission to ICU, and the reactivation incidence of HCMV was 20.83%. There was no significant difference in gender, age, body mass index (BMI), underling disease reasons for ICU transfer (except sepsis), basic vital signs, disease severity scores, or laboratory findings including infection, immune, blood routine, liver, kidney and circulatory indicators except neutrophils count (NEU), hypersensitivity C-reactive protein(hs-CRP), hemoglobin (Hb), blood urea nitrogen (BUN), N-terminal pro-brain natriuretic peptide (NT-proBNP) between the two groups. The height (cm: 160±6 vs. 166±8), body weight (kg: 49.4±11.2 vs. 57.6±10.5), Hb (g/L: 87±18 vs. 104±24) in HCMV reactivation group were significantly lower than non-reactivation group, as well as NEU [×10 9/L:12.7 (9.9, 22.5) vs. 8.9 (6.2, 13.8)], hs-CRP [mg/L: 115.5 (85.2, 136.6) vs. 39.9 (17.5, 130.2)], BUN [mmol/L:13.7 (8.9, 21.5) vs. 7.1 (4.9, 10.5)] and NT-proBNP [ng/L: 6 751 (2 222, 25 449) vs. 1 469 (419, 4 571)] within 24 hours of admission to ICU. The prevalence of sepsis [60.0% (6/10) vs. 15.8% (6/38)], blood transfusion [100.0% (10/10) vs. 60.5% (23/38)], hospitalization expense [ten thousand yuan: 35.7 (25.3, 67.1) vs. 15.2 (10.4, 22.0)], 90-day all-cause mortality [70.0% (7/10) vs. 21.1% (8/38)], length of ICU stay [days: 26 (16, 66) vs. 14 (9, 19)], the duration of mechanical ventilation [days: 26 (19, 66) vs. 13 (8, 18)] in HCMV reactivation group were significantly higher than non-reactivation group, and there were significant statistical differences between the two groups (all P < 0.05). Logistic regression analysis showed that sepsis was an independent risk factor for HCMV reactivation in immunocompetent mechanical ventilation severe pneumonia patients with mechanical ventilation [odds ratio ( OR) = 9.35, 95% confidence interval (95% CI) was 1.72-50.86, P = 0.010]. Conclusions:HCMV infection is very common in immunocompetent severe pneumonia patients on mechanical ventilation and incidence of HCMV reactivation is high. Moreover, HCMV reactivation could adversely affect clinical prognoses, and sepsis may be a risk factor for HCMV reactivation.
6.Incidence and risk factors of active human cytomegalovirus infection in patients with severe community-acquired pneumonia
Zhihui ZHANG ; Zhan WU ; Jierong ZHANG ; Jiaqi LIANG ; Minmin XU ; Sibei CHEN ; Xuesong LIU ; Yonghao XU ; Ling SANG ; Weiqun HE ; Yimin LI ; Xiaoqing LIU
Chinese Journal of Experimental and Clinical Virology 2021;35(4):389-394
Objective:To investigate the incidence and risk factors of active human cytomegalovirus (HCMV) infection in patients with severe community-acquired pneumonia.Methods:Patients who required respiratory support and were diagnosed with severe community-acquired pneumonia in the respiratory intensive care unit (RICU) of the First Affiliated Hospital of Guangzhou Medical University from March 1, 2019 to June 1, 2020 were consecutively screened and divided into active HCMV infection group (20 cases) and non-active HCMV infection group (95 cases) based on whether a patient has active HCMV infection or not. Differences in demographic data, laboratory findings, and clinical outcomes were compared between the two groups. Moreover, logistic regression was applied to analyze risk factors for active HCMV infection.Results:The 20 of 115 patients with severe community-acquired pneumonia requiring respiratory support were confirmed to have active infection with HCMV, with a prevalence of active HCMV infection of 17.4%. The pneumonia severity index (PSI) and suppressor T lymphocytes (Ts) in active HCMV infection group were higher than that of the control group, and all the differences were statistically significant ( Z=2.432, P=0.015; Z=2.036, P=0.042); whereas lymphocytes, monocytes, blood lactate, and platelet levels were lower than those of the control group, and all the differences were statistically significant ( P < 0.05). Patients with active HCMV infection had a higher transfusion rate than the control group, and the differences were statistically significant (χ 2=3.941; P=0.047). Increasing levels of PSI and Ts percentage were independent risk factors for active HCMV infection ( OR=1.03, 95% CI: 1.01~1.05; OR=1.06, 95% CI: 1.00~1.11; P < 0.05). RICU length of stay, complication rates, and 90-day all-cause mortality were higher in the active HCMV infection group than the control group, and all the differences were statistically significant ( P < 0.05). Conclusions:Active HCMV infection is highly prevalent in patients with severe community-acquired pneumonia and associated with several adverse clinical outcomes, with PSI and Ts cell levels being independent risk factors.
7.Study on the sleep quality and emotional state of flying personnel
Hua GE ; Cong WA ; Shuang BAI ; Andong ZHAO ; Dalong GUO ; Zhihui YANG ; Hao ZHAN ; Feng WU
Chinese Journal of Aerospace Medicine 2018;29(3):205-209
Objective To investigate the sleep quality ,emotional state and their relationship for flying personnel so as to provide reference for the targeted aeromedical support. Methods Two hundred and forty-nine flying personnel participated in the anonymous questionnaire surveys ,including Pittsburgh sleep quality index (PSQI) ,self-evaluation of anxiety scale (SAS) ,self-rating depression scale (SDS ) , and profile of mood state (POMS ).Comparisons of sleep quality among flying personnel ,norm and ordinary soldiers were conducted.The correlation between sleep quality and emotional state was analyzed then. Results There were 238 questionnaires returned and the effective rate was 95.6%.The prevalence of sleeping disorders in 238 flying personnel was 36.6%.Their total score of PSQI was (6.79 ± 3.06) ,which was significantly higher than that of norm and ordinary soldiers (t= 14.706 ,5.967 , P<0.01) and their scores of anxiety and depression were higher than those of the domestic norm (t=4.867 ,3.147 , P<0.01).In addition ,with the total score of PSQI increased the scores on SAS , SDS , tension-anxiety , depression-dejection , anger-hostility , fatigue-inertia and confusion-bewiderment showed upward trend.But the score on vigor-activity was decreased.Correlation analysis showed that the total score of PSQI was positively correlated with the scores on SAS , SDS , tension-anxiety , depression-dejection , anger-hostility , fatigue-inertia and confusion-bewiderment (r=0.549-0.665 ,P<0.01) ,and was negatively correlated with vigor-activity (r= -0.417 , P< 0.01 ). Conclusions Sleep quality is an important indicator of emotional state. Sleep quality of flying personnel is lower than that of norm and ordinary soldiers and this means the flying personnel are in obviously higher tension and stress state.
8.Study on the sleep quality and emotional state of flying personnel
Hua GE ; Cong WA ; Shuang BAI ; Andong ZHAO ; Dalong GUO ; Zhihui YANG ; Hao ZHAN ; Feng WU
Chinese Journal of Aerospace Medicine 2018;29(3):205-209
Objective To investigate the sleep quality ,emotional state and their relationship for flying personnel so as to provide reference for the targeted aeromedical support. Methods Two hundred and forty-nine flying personnel participated in the anonymous questionnaire surveys ,including Pittsburgh sleep quality index (PSQI) ,self-evaluation of anxiety scale (SAS) ,self-rating depression scale (SDS ) , and profile of mood state (POMS ).Comparisons of sleep quality among flying personnel ,norm and ordinary soldiers were conducted.The correlation between sleep quality and emotional state was analyzed then. Results There were 238 questionnaires returned and the effective rate was 95.6%.The prevalence of sleeping disorders in 238 flying personnel was 36.6%.Their total score of PSQI was (6.79 ± 3.06) ,which was significantly higher than that of norm and ordinary soldiers (t= 14.706 ,5.967 , P<0.01) and their scores of anxiety and depression were higher than those of the domestic norm (t=4.867 ,3.147 , P<0.01).In addition ,with the total score of PSQI increased the scores on SAS , SDS , tension-anxiety , depression-dejection , anger-hostility , fatigue-inertia and confusion-bewiderment showed upward trend.But the score on vigor-activity was decreased.Correlation analysis showed that the total score of PSQI was positively correlated with the scores on SAS , SDS , tension-anxiety , depression-dejection , anger-hostility , fatigue-inertia and confusion-bewiderment (r=0.549-0.665 ,P<0.01) ,and was negatively correlated with vigor-activity (r= -0.417 , P< 0.01 ). Conclusions Sleep quality is an important indicator of emotional state. Sleep quality of flying personnel is lower than that of norm and ordinary soldiers and this means the flying personnel are in obviously higher tension and stress state.
9.Medium-and long-term results of one-stage debridement and total hip arthroplasty for advanced active tuberculosis of the hip
Yongqing WANG ; Hongbin BI ; Zhihui ZHAO ; Ying ZHAN ; Zhiqiang YANG ; Jingsheng WANG
Chinese Journal of Orthopaedics 2013;33(9):895-900
Objective To observe the medium-and long-term results of one-stage debridement and total hip arthroplasty (THA) for advanced active tuberculosis of the hip.Methods From January 2002 to December 2008,8 patients (9 hips) with advanced active tuberculosis of the hip underwent one-stage debridement and THA in our hospital.There were 5 males and 3 females,aged from 18 to 59 years (average,39.6 years).According to Babhuulkar and Pande imaging classification,there were 1 case of grade Ⅲ and 7 cases of grade Ⅳ.All patients had hip pain,which got serious during active and passive motion.All patients had dysfunction in stretch,abduction,rotation and flexion of the hip,and the flexion deformity ranged from 30° to 70° (average,46°).Thomas sign were positive in all patients.The erythrocyte sedimentation rate ranged from 45 to 125 mrr/1 h.The results of tuberculin test were all positive.X-rays showed osteoclasia,narrowing or disappearance of the joint space and surrounding abscess in all patients.The diagnosis of hip joint tuberculosis was confirmed by postoperative pathological examination in all patients.All patients were treated with antituberculous medications for 12 to 18 months,including preoperative IRES (≥ 2 weeks) and postoperative IRES (3 months),IRE (6 to 9 months) and IR (3 to 6 months).Results All patients were followed up for 50 to 150 months (average,88.8 months).One-stage healing of incision was obtained in all patients.X-rays showed no signs about loosening of prosthesis and recurrence of tuberculosis.The erythrocyte sedimentation rate returned to normal range within 6 months after operation.The average Harris score improved from preoperative 25.78±16.15 to 94.78±2.91 at final follow-up,and the difference was significant.Conclusion Under the standard antituberculosis chemotherapy,the one-stage debridement and THA are safe and feasible for advanced active tuberculosis of the hip,which can result in satisfactory medium-and long-term resuits.
10.Inhibitory effect of tanshinone II A on TGF II-β1-induced cardiac fibrosis.
Daixing ZHOU ; Zhihui LI ; Liwei ZHANG ; Chengye ZHAN
Journal of Huazhong University of Science and Technology (Medical Sciences) 2012;32(6):829-833
This study examined the effect of tanshinone II A (TSN II A) on the cardiac fibrosis induced by transforming growth factor β1 (TGF-β1) and the possible mechanisms. Cardiac fibroblasts were isolated from cardiac tissues of neonatal Sprague-Dawley (SD) rats by the trypsin digestion and differential adhesion method. The cells were treated with 5 ng/mL TGF-β1 alone or pretreated with TSN II A at different concentrations (10(-5) mol/L, 10(-4) mol/L). Immunocytochemistry was used for cell identification, RT-PCR for detection of the mRNA expression of connective tissue growth factor (CTGF) and collagen type I (COL I), Western blotting for detection of the protein expression of Smad7 and Smad3, and immunohistochemistry and immunofluorescence staining for detection of the protein expression of phosphorylated Smad3 (p-Smad3), CTGF and COLI. The results showed that TGF-β1 induced the expression of CTGF, COL I, p-Smad3 and Smad7 in a time-dependent manner. The mRNA expression of CTGF and COL I was significantly increased 24 h after TGF-β1 stimulation (P<0.01 for all). The protein expression of p-Smad3 and Smad7 reached a peak 1 h after TGF-β1 stimulation, much higher than the baseline level (P<0.01 for all). Pretreatment with high concentration of TSN A resulted in a decrease in the expression of p-Smad3, CTGF and COL I (P<0.01). The protein expression of Smad7 was substantially upregulated after pretreatment with two concentrations of TSN II A as compared with that at 2 h post TGF-β1 stimulation (P<0.05 for low concentration of TSN I IA; P<0.01 for high concentration of TSN II A). It was concluded that TSN II A may exert an inhibitory effect on cardiac fibrosis by upregulating the expression of Smad7, suppressing the TGF-β1-induced phosphorylation of Smad3 and partially blocking the TGF-β1-Smads signaling pathway.
Animals
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Diterpenes, Abietane
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pharmacology
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Fibrosis
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metabolism
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Heart
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physiopathology
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Rats
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Rats, Sprague-Dawley
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Transforming Growth Factor beta1
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metabolism

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