1.Protective effects of TAK-242 against coronary microembolization in rat associated with involvement of TLR4/NF-κB signaling pathway
Xiantao WANG ; Lang LI ; Yuanxi LU ; Yuhan SUN ; Wenkai HE ; Jiabao LIANG
Chinese Journal of Emergency Medicine 2017;26(7):745-750
Objective To investigate the role of TLR4/NF-κB signaling pathway under the action of TAK-242 in the cardiomyocyte apoptosis after coronary micro-embolism (CME) in rats.Methods Fortyfive rats were randomized (random number) into three groups:sham operation,CME and CME plus TAK242 groups (n =15 per group).CME was induced by injecting polyethylene microspheres (42 μm) into the left ventricle except the sham group.CME plus TAK-242 group was treated with TAK-242 (2 mg/kg) via the tail vein of mice 30 min before CME modeling.Cardiac function was evaluated 6 h after operation.Tissue biopsy was stained with HBFP to measure the size of infarction area.TUNEL assay was used to detect cardiomyocyte apoptosis.Western blot and qPCR were used to evaluate the protein levels and mRNA expressions of TLR4,NF-κB p65 and cleaved caspase-3,respectively.Statistical analysis was performed using one-way analysis of variance followed by LSD-t test.Results Compared with the sham group,left ventricular ejection fraction (LVEF) in the CME group was significantly decreased [(68.91 ± 4.12) % vs.(84.80 ± 2.51) %,P < 0.05],and the infarction area (P < 0.05),the apoptosis index [(3.36 ± 0.63) % vs.(0.19 ± 0.08) %,P <0.05],the mRNA expressions of TLR4,NF-κB p65 and cleaved caspase-3 in CME group were increased significantly (all P < 0.05).Compared with CME group,LVEF in the CME plus TAK-242 group was significantly improved [(75.58 ± 5.01) % vs.(68.91 ± 4.12) %,P<0.05],and the infarction area [(8.58 ± 2.12) % vs.(14.65 ± 4.23) %,P<0.05],the apoptosis index [(1.43 ± 0.51) % vs.(3.36 ± 0.63) %,P < 0.05],the mRNA expressions of TLR4,NF-κB p65 and cleaved caspase-3 in CME + TAK-242 group were decreased significantly (all P < 0.05).Conclusions TAK-242 effectively improved CME-induced cardiac dysfunction by regulating TLR4/NF-κB signaling pathway and then reducing the cardiomyocyte apoptosis.
2.Effect of pretreatment with diallyltrisulfide on cardiomyocyte apoptosis after coronary microembolization in rats
Jiabao LIANG ; Lang LI ; Wenkai HE
The Journal of Practical Medicine 2018;34(3):371-375
Objective To investigate the effect of diallyltrisulfide on rats with myocardial injury after coro-nary microembolization (CME). Methods 20 survival of SD rats were randomly divided into CME group (CME group)and diallyltrisulfide pretreatment group(DATSgroup),and these rats were injected with microspheres(42 μm in diameter)into the left ventricles to induce the model of CME, 10 rats for each group.DATS group was received diallyltrisulfide (DATS) 40 mg/(kg·d) for 7 days before operation. Another 10 survival of SD rats was selected as sham operation group(Sham group),and these rats were injected with the same dose of normal saline by left ventri-cles. Cardiac function was assessed by echocardiography and the expression of Akt and caspase-3 of myocardial tissue of rats in each group were detected by TUMEL staining,RT-PCR and Western Blot,while testing the level of cTnI after operation of 6 h. Results Compared with Sham group, the cardiac function of CME group and DATS group was significantly decreased (P<0.05), the expression of caspase3 mRNA and protein was significantly increased (P<0.05), the expression on Akt mRNA and protein was significantly decreased (P<0.05) (P<0.05). Com-pared with CME group, the cardiac function of DATS group was significantly improved (P<0.05), the expression of caspase3 mRNA and protein was significantly decreased (P<0.05), the expression of Akt mRNA and protein was significantly increased (P<0.05), cTnI level was significantly decreased (P<0.05). Conclusion Diallyltrisulfide pretreatment can significantly reduce the apoptosis of cardiomyocytes after CME and improve cardiac function.The mechanism may be through the inhibition of Akt to activate cardiomyocyte caspase3-mediated death receptor activa-tion pathway.
3.The quality of life and its influencing factors in high risk population of stroke in district
Liang YIN ; Yejing WANG ; Yunfang JI ; Wenjun LIU ; Jiabao GAO ; Minqi ZHOU ; Lichen YANG
Chinese Journal of Behavioral Medicine and Brain Science 2021;30(9):832-837
Objective:To understand the quality of life of high risk population of stroke in community and analyze the influencing factors.Methods:Four community health service centers in Huangpu District were randomly selected, and the subjects were included by using convenient sampling method among the high risk groups of stroke found in the community stroke screening and prevention and control project in Shanghai.The World Health Organization quality of life scale-brief form questionnaire(WHOQOL-BREF), self-rating depression scale (SDS) and self-rating anxiety scale (SAS) were used as the survey tools to study 1200 high-risk stroke subjects.Single sample t-test was used to compare the differences between the scores and the data of 24 centers in the world, and multiple linear stepwise regression were used to analyze the influencing factors. Results:The scores of physical field, psychological field and social relationship field ((13.60±1.86), (14.58±1.97), (13.72±2.10)respectively) of high-risk population of stroke were lower than the scores of general population of 24 centers in the world ( P<0.01), and the scores of environmental field (14.08±1.95) were higher than it ( P<0.01), of which the differences were all statistically significant.The results of multiple linear stepwise regression analysis showed that old age, anxiety and depression were the risk factors influencing the scores of physical field( β=-0.027, -0.056, -0.051), psychological field( β=-0.019, -0.055, -0.050) and environmental field( β=-0.017, -0.040, -0.054); old age and depression were the risk factors influencing the scores of social relationship field( β=-0.026, -0.067); anxiety and depression were the risk factors influencing the self-assessment of quality of life and health ( β=-0.012, -0.014 for quality of life; -0.012, -0.014 for health, all P<0.01). Conclusion:The quality of life of high-risk population of stroke may be related to age, depression, anxiety and other psychological factors.The prevention and treatment of stroke should take both physical and mental measures, take timely intervention for poor psychological status, and gradually improve the quality of life.
4.Study on Anti-inflammatory Effect and Its Mechanism of the Extract of Dcsmodium microphyllum
Huazhen SU ; Xiuneng TANG ; Jiangcun WEI ; Jiabao MA ; Yong CHEN ; Liqing LIANG ; Xianzai JIANG ; Qian HAN
China Pharmacy 2019;30(18):2532-2536
OBJECTIVE: To study the anti-inflammatory effect and its mechanism of the extract of Dcsmodium microphyllum, so as to provide experiment reference for further study of D. microphyllum. METHODS: Acute inflammatory model was established by xylene,glacial acetic acid and carrageenan. Using dexamethasone as positive control (0.005 g/kg), inhibitory effects of intragastric different doses of the extract of D. microphyllum (50, 30, 15 g/kg) on xylene-induced ear swelling in normal mice and adrenalectomized mice, glacial acetic acid-induced permeability increasing of abdominal capillaries in normal mice, carrageenan- induced paw swelling in normal mice and adrenalectomized mice were investigated. The levels of MDA, SOD and NO in the inflammatory tissue of toes of adrenalectomized mice were detected in carrageenan-induced inflammation model. Blank group was set for control (ig. equal volumn of water). RESULTS: Compared with blank group, ear swelling degree of normal mice and adrenalectomized mice were decreased significantly in D. microphyllum extract high-dose and medium-dose groups while inhibitory rate of ear swelling was increased significantly; the permeability of abdominal capillaries of normal mice was significantly decreased in D. microphyllum extract groups; the swelling degree of toes in normal mice of D. microphyllum extract high-dose and middle-dose groups and adrenalectomized mice were significantly decreased while inhibitory rate of toe swelling was increased significantly (P<0.05 or P<0.01). The levels of MDA and NO in the toe inflammatory site of adrenalectomized mice were decreased significantly in D. microphyllum extract high-dose and medium-dose groups, while the level of SOD was increased significantly (P<0.05). CONCLUSIONS: D. microphyllum extract can inhibit acute inflammation in mice significantly. Its anti-inflammatory mechanism is associated with decreasing MDA and NO while increasing SOD levels, and the anti-inflammatory effect does not depend on the hypothalamus-pituitary-adrenal axis system.