[Chronic Injury of Mice Bone Marrow Multipotent Hematopoietic Progenitor Cells Induced by Ionizing Radiation].

OBJECTIVE: To explore the chronic injury and its possible mechanism of ionizing radiation on multipotent hematopoietic progenitor cells (MPPs) by determining the related indicators of MPPs in bone marrow of mice post-radiation. METHODS: Sixteen C57BL/6 adult mice were randomly divided into normal control and irradiation groups, 8 mice in each group. The mice in irradiation group were exposed to 6 Gy X-ray. The proportion of bone marrow MPPs, their apoptosis and proliferation 2 months after irradiation were detected by flow cytometry. Mitochondrial activity and levels of reactive oxygen species (ROS) in each MPPs population were detected by Mitotracker Red and DCFDA probes, and the senescent state of MPPs in the bone marrow was analyzed. RESULTS: Ionizing radiation could reduce the proportion of MPPs in mouse bone marrow. The proportions and numbers of MPP1, MPP3 and MPP4 in the bone marrow were significantly decreased after whole-body irradiation with 6 Gy X-ray (P<0.05). In addition, radiation significantly reduced the colony-forming capacity of MPPs in bone marrow (P<0.05), the proportions of apoptotic cells in the MPP1 and MPP4 cell populations increased significantly in the bone marrow (P<0.05). The activity of mitochondria was significantly reduced in the bone marrow MPP2, MPP3 and MPP4 cell populations compared with that of the control group (P<0.05). It was also found that the radiation could significantly increase the ROS levels of MPPs in bone marrow, and the content of ROS in the MPP2, MPP3 and MPP4 cell population of the bone marrow was significantly increased(P<0.05). The senescent cells ratios of MPP1, MPP3 and MPP4 cells in the bone marrow after irradiation were significantly higher than those in the control group (P<0.05). CONCLUSION: Ionizing radiation can cause chronic MPPs damage in mice, which is closely associated with persistent oxidative stress, cells apoptosis, and cellular senescence.

Impairment and Regeneration of Gastric Mucosa After Irradiation in Mice.

OBJECTIVE: To understand the effects of γ-ray irradiation (IR) on the proliferation of gastric mucosal cells and to investigate the possible mechanisms that affect gastric mucosal cell proliferation. STUDY DESIGN: C57BL/6J mice were exposed to IR at various doses (4, 8, and 15 Gy). We measured the changes of gastric mucosal BrdU-positive cells and the expression of ß-catenin protein in the isthmus of fundic glands at days 1, 3, and 5 after irradiation. RESULTS: Our data showed that the mice that received 15 Gy IR died within 4 days. IR caused gastric mucosal injury in mice, and the degree of injury increased along with the increasing doses. Compared with the control group, the proliferation of gastric mucosal cells was inhibited 1 day after irradiation. Cell proliferation was recovered on day 5 after low-dose (4 and 8 Gy) IR, while proliferation was continuously inhibited after high-dose (15 Gy) IR. ß-catenin expression was increased and had a translocation in the isthmus of gastric mucosa. CONCLUSION: These findings suggest that gastric mucosa is sensitive to irradiation. The Wnt/ß-catenin pathway is activated and plays a role in cell proliferation of gastric mucosa upon irradiation.

Exploration of P2X3 in the rat stellate ganglia after myocardial ischemia.

ATP is implicated in peripheral pain signaling by actions on P2X receptors, especially P2X(3) receptor. Cardiac primary afferents running in the sympathetic nerves are considered to be essential pathways for transmission of cardiac nociception to the central nervous system. Because little is known about P2X(3) involvement in cardiac nociception, this study observed the difference in P2X(3) localization and expression in stellate ganglia (SG) from naive rats and in a pathological model of myocardial ischemic injury induced by repeated subcutaneous isoprenaline injections. Distribution of P2X(3) and morphometry of neurons in SG were investigated by immunohistochemistry, Western blotting, in situ hybridization (ISH) and by sterological study. Diffuse cytoplasmic P2X(3) immunolabelling was observed by light microsocopy. No nuclear labeling was detected. The intensity of P2X(3) labeling in the experimental myocardial ischemic injury group was increased in relation to that of the control group. Numerical densities of stellate ganglion neurons in the experimental group were higher than those of the control group. By Western blotting and ISH, the signals of P2X(3) protein and its mRNA in the myocardial ischemic group were higher than those of the control group. The P2X(3) labeling intensity and the numerical density in SG of the experimental myocardial ischemic injury group were enhanced, suggesting the involvement of P2X(3) receptor for the transmission of pain after myocardial ischemic injury.

[Cardioprotective effects of sodium ferulate mediated by nitric oxide on ischemia-reperfusion injured myocardium: experiment with isolated rat hearts].

OBJECTIVE: To investigate the cardioprotective effects of sodium ferulate (SF) mediated by nitric oxide on ischemia-reperfusion injured myocardium. METHODS: Fifty-six SD rats were killed. Their hearts were isolated and randomly divided into 7 equal groups: ischemia/reperfusion group (I/R group), ischemic/preconditioning (IP group, to be perfumed with anoxic and reoxygenated fluid several times so as to produce protection against continuous and severe ischemia), SF pretreatment group (to be perfused with fluid with SF and then made I/R model), L-NAME + SF group (to be perfused with fluid with SF and L-NAME, a NO inhibitor, and then made I/R model), glibenclamide (Glib) + SF group (to be perfused with Glib + SF and then made I/R model)), L-NAME + Glib + SF group (to be perfused with L-NAME + Glib + SF and then made I/R model)), and control group (normal isolated hearts). Electrocardiography was conducted and left ventricular systolic pressure (LVSP), dp/dt(max), and heart rate (HR) were measured. By the end of the experiment 0.5 grams of tissue was taken from the left ventricle. The levels of superoxide dismutase (SOD), malonyldialdehyde (MOD), NO, and cyclic guanosine monophosphate (cGMP) were detected. RESULTS: The levels of LVSP, dp/dt(max), and HR of the SF pretreatment group and IP group were all significantly higher than those of the I/R group (all P < 0.01) without significant differences between these 2 groups (all P > 0.05). The levels of LVSP, dp/dt(max), and HR of the L-NAME, Glib + SF, and L-NAME + Glib + SF groups were all significantly lower than those of the SF pretreatment group and IP group (all P < 0.01). Ventricular extrasystole (VE) and ventricular tachycardia (VT) during re-perfusion period occurred in all hearts of the I/R group, however, the incidence rates of VE and VT of the IP and SF groups were all significantly lower than those of the I/R group (all P < 0.01), however, without significant differences between the IP and SF groups (all P > 0.05). The incidence rate of VE and VT of the L-NAME, Glib + SF, and L-NAME + Glib + SF groups were all significantly higher than those of the SF group (all P < 0.01). The myocardium MDA content of the I/R group was significantly higher and the SOD activity significantly lower in comparison with the control group (both P < 0.01); the myocardium MDA contents of the IP and SF groups were significantly lower and the SOD activity levels significantly higher in comparison with the I/R group (all P < 0.01), however, with significant differences between theses 2 groups (both P > 0.05); the myocardium MDA contents were significantly higher and the SOD activity levels significantly lower in the L-NAME, Glib + SF, and L-NAME + Glib + SF groups in comparison with the SF and IP groups (all P < 0.01). The myocardium NO(2)(-)/NO(3)(-) and cGMP contents of the I/R group were both significantly lower than those of the control group (both P < 0.01), and the myocardium NO(2)(-)/NO(3)(-) and cGMP contents of the IP and SF groups were both significantly higher than those of the I/R group (both P < 0.01), however, without significant differences between these 2 groups (both P > 0.05). The myocardium NO(2)(-)/NO(3)(-) and cGMP contents of the L-NAME, Glib + SF, and L-NAME + Glib + SF groups were all significantly lower than those of the SF group (all P < 0.01). CONCLUSION: SF pretreatment significantly improves the releasing of NO, decreases oxygen free radicals, and relieves myocardial ischemia reperfusion injury. The opening of the ATP-sensitive potassium channels induced by the cGMP way of NO activation may be an important pathway in the cardioprotective effects of SF pretreatment.