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Background The chronic injury of the hematopoietic system caused by ionizing radiation (IR) is often ignored. The essential cause of this injury is the damage of hematopoietic stem and progenitor cells (HSPCs). Objective To explore the long-term effects of IR at different radiation doses and at different radiation fractions of the same radiation dose on HSPCs in the bone marrow of mice, and to provide a scientific basis for reducing the chronic damage to the hematopoietic system caused by IR. Methods A total of 16 male C57BL/6 mice aged 8-10 weeks were randomly divided into four groups that received different doses or fractions of total body X-ray irradiation, including 1.5 Gy×4 irradiation group (n=5), 3 Gy irradiation group (n=4), 6 Gy irradiation group (n=4), and non-irradiation group (n=3). Two months after irradiation, bone marrow cells from each mouse were collected and counted. The clone forming ability of bone marrow cells was analyzed by cobblestone area-forming cell (CAFC) assay. The proportion of HSPCs was measured by flow cytometry. The cell cycle of HSPCs was assessed by antigen identified by monoclonal antibody Ki 67 (Ki-67) and 7-amino-actinomycin D (7-AAD) double staining. The reactive oxygen species (ROS) levels of HSPCs were estimated with a 2,7-dichlorodihydrofluorescein diacetate (DCFDA) probe. The cellular senescence of HSPCs was evaluated with a 5-dodecanoylaminofluorescein di-β-D-galactopyranoside (C12FDG) probe. The expression of senescence related genes such as P16, P19, P21, and P27 was measured by real-time fluorescence quantitative PCR. Results There was no significant change in the numbers of bone marrow cells 2 months after different doses and fractions of radiation (P>0.05). The clone forming ability of bone marrow cells was significantly decreased after 3 Gy and 6 Gy irradiation when compared to non-irradiated mice (P<0.01). HSPCs responded inconsistently to different doses and fractions of irradiation. Overall, there was no significant change in long-term hematopoietic stem cells (LT-HSCs) proportion after irradiation (P>0.05), the proportions of hematopoietic progenitor cells (HPCs), hematopoietic stem cells (HSCs), short-term hematopoietic stem cells (ST-HSCs), and multipotent progenitors 2 (MPP2) increased after irradiation (P<0.05), and the proportions of LSK, MPP1, MPP3, and MPP4 cells decreased after irradiation (P<0.05); except for HPCs and MPP2, the proportion of HSPCs in G0 phase was decreased (P<0.05). The ROS production in HSPCs was increased significantly after 6 Gy irradiation (P<0.05), while the ROS levels after 3 Gy and 1.5 Gy×4 irradiation were similar to that of the non-radiation group (P>0.05). The cellular senescent proportion of HPCs, LSK, and HSCs increased after irradiation (P<0.05). The expression levels of senescence related genes P16, P19, and P21 in HSCs were significantly increased (P<0.05). Conclusion The responses of HSPCs in bone marrow to IR vary depending on doses and fractions of irradiation. Increased ROS production and cellular senescence may be involved in the damage process of HSPCs under radiation settings.
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0.05). Conclusions One mechanism of SF pretreatment cardioprotective effect is mediated by bradykinin. The combined use of SF and CP doesn′t result in significant improvement, and thenefore is not advocated.
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Aim To study the protective effects of pharmacological preconditioning induced by sodiumferulate(SF)on isolated rat heart and its machanisms.Methods Isolated SD rat hearts were divided randomly into 5 groups : Control group (hearts were perfused by oxygenated perfusate for 100 minutes); Ischemia/Reperfusion(I/R) group (hearts suffered from 40 min global ischemia/30 min reperfusion after oxygenated perfusate for 30 minutes); Ischemia preconditioning group(hearts were preconditioned by 3 periods of 5-minute global ischemia/5-minute reperfusion before it suffered from I/R); SF group (previously hearts were perfused with oxygenated perfusate administered with 1.69 mmol?L-1 SF then subjected to I/R); Glibenclamide group (previously hearts were perfused with oxygenated perfusate administered with 1.69 mmol?L-1SF and 30 ?mol?L-1 Glibenclamide before it suffered from I/R). Results Compared with I/R group, 1.69 mmol?L-1 SF precondition improved significantly heart function, reduced the incidence and severity of ventricular arrhythmias, alleviated calcium overload in myocardial cell; furthered activities of Na+,K-ATPase and Ca2+-ATPase in myocardium. These effects were attenuated by 30 ?mol?L-1 Glibenclamide.Conclusions SF precondition can improve heart function and resist arrhythmia and Ca2+-overload. The cardioprotective effects of SF precondition maybe related with the opening of ATP-sensitive potassium (KATP) channels.
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Aim To investigate effects of tetramethylpyrazine (TMP) on neuropathic pain induced by P2X_3 receptor. Methods Chronic constriction injury (CCI) model was adopted. Mechanical withdrawal threshold and thermal withdrawal latency were measured and P2X_3 immunoreactivity in L_4/L_5 spinal cord was detected by immunohistochemistry. Results At day 14 after operation, the mechanical withdrawal threshold and thermal withdrawal latency in group Ⅴ(CCI group) were lower than those in groupⅠ(NS group),Ⅱ(TMP group),Ⅲ(sham group) and Ⅳ (CCI+ TMP group)(P0.05). The expression of P2X_3 receptor in L_4/L_5 spinal cord of group Ⅳ was lower than that of group Ⅴ (P