1.Protective effects and mechanism of penehyclidine hydrochloride on myocardial ischemia-reperfusion injury in mice
Chunmei JIA ; Chenxue MENG ; Baohui ZHANG ; Shuai HAN ; Congna ZI
China Pharmacy 2024;35(24):3010-3015
OBJECTIVE To investigate the protective effects and potential mechanism of penehyclidine hydrochloride (PHC) on myocardial ischemia-reperfusion (I/R) injury in mice through the macrophage migration inhibitory factor (MIF)/adenosine monophosphate-activated protein kinase (AMPK) signaling pathways. METHODS Male C57BL/6 mice were randomly divided into sham operation group, I/R group, I/R+PHC group (PHC 20 μg/kg), I/R+ISO-1 group (MIF inhibitor 35 mg/kg), I/R+ PHC+ISO-1 group (with the same dosage as each single drug group), with 8 mice in each group. Except for the sham operation group, the myocardial I/R injury model was prepared by coronary artery ligation. Thirty minutes before ligation, mice in each drug group were injected with 1 mL of the corresponding drug solution through the tail vein. After 120 min of reperfusion, the levels of cardiac function indexes [heart rate, stroke volume, ejection fraction, cardiac output, left ventricular posterior wall thickness in systole (LVPWs), left ventricular posterior wall thickness in diastole (LVPWd)], serum inflammatory factors [interleukin-6 (IL- 6), IL-10, tumor necrosis factor-α (TNF-α)] in mice were detected in each group; the pathological changes and ultrastructure of myocardial tissue were observed, and the protein expressions of B cell lymphoma-2 (Bcl-2), phosphorylated AMPKα (p-AMPKα) and MIF in myocardial tissue were detected. RESULTS Compared with the sham operation group, the myocardial cells in the I/R group were loosely arranged, with severe infiltration of inflammatory cells and obvious mitochondrial damage. Serum levels of IL-6 and TNF-α and protein expression of p-AMPKα in myocardial tissue were significantly increased or upregulated, while heart rate, stroke volume, ejection fraction, cardiac output, LVPWd and serum level of IL-10 were significantly decreased (P<0.05). Compared with the I/R group, the myocardial tissue lesions in the I/R+PHC group were alleviated; serum levels of IL-6 and TNF-α were decreased significantly, while heart rate, stroke volume, ejection fraction, cardiac output, LVPWs, LVPWd, serum level of IL-10, and protein expressions of Bcl-2, p- AMPKα and MIF in myocardial tissue were significantly increased or upregulated (P<0.05). However, myocardial tissue lesions of mice in the I/R+ISO-1 group worsened, with most quantitative indicators significantly deteriorating (P<0.05); MIF inhibitor could generally reverse the protective effect of PHC on I/R mice (P<0.05). CONCLUSIONS PHC can improve cardiac function, reduce myocardial inflammation, and restore the ultrastructure of myocardial tissue in I/R mice. These effects may be related to the activation of the MIF/AMPK signaling pathway.
2.Evaluation of point-of-care testing for D-dimer in elderly patients
Zeng ZENG ; Hongmei JIAO ; Chenxue QU ; Dan SUN ; Jiali DU ; Dongfang WEI ; Meng CHEN
Chinese Journal of Emergency Medicine 2016;25(8):1049-1053
Objective To evaluate the clinical performance of AQT90 FLEX,a novel time-resolved fluorescence based point-of-care test (POCT) for quantification of D-dimer in elderly patients.Methods The method from Quantitative D-dimer assay (WS/T 477-2015) for testing equipment performance was used as a reference to evaluate the clinical performance of AQT90 FLEX.The correlation was compared between testing results of D-dimer using the AQT90 immune-assay analyzer and those using the ACL TOP coagulation analyzer.Results At high concentration of D-dimer,the within-run precision coefficient of variation (CV)was 2.619%,and at low concentration of D-dimer,the within-run precision CV was 2.767%.The pollution-carrying rate was 0.12%.The measured data from AQT90 and ACL TOP had a correlation coefficient of r =0.9491 (P < 0.01).The equation of the line of best fit for D-dimer with which all AQT90 results can be adapted to the ACL TOP was:AQT90 =2.52 ACL TOP + 0.15.The number from the equation was slightly greater in female than that in male,and it was also increased in elderly.Conclusions The AQT90 FLEX had rational precision and linearity in determination of concentration.There was a high agreement between the testing results from AQT90 and those from ACL TOP.It was recommended to use a slope of 2.52 and an intercept of 0.15 to adjust the D-dimer values of the ACL TOP to the AQT90 FLEX assay systems.POCT for D-dimer by AQT90 FLEX raises feasibility for use in elderly patients.

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