为了阐明大气污染物SO2对神经系统和心血管系统的毒作用机制，采用全细胞膜片钳技术研究了SO：衍生物（NaHSO，和Na2S0，分子比为1∶3）对大鼠海马、背根节神经元和心肌细胞膜上钠、钾、钙离子通道的影响。结果显示：（1）SO2衍生物可显著增大大鼠海马CAl区神经元钠电流，不影响钠通道的激活过程，但可使钠电流的失活曲线向去极化方向移动，延迟钠通道的失活过程；另外，SO2衍生物可显著增大瞬间外向钾电流（IA）和延迟整流钾电流（IK），不影响IA的激活过程，使IK 的激活过程向负电压方向移动，促进IK的激活过程，而使IA 的失活曲线向正电压方向移动，延迟IA的失活过程。（2）SO2 衍生物显著增大鼠背根节神经元钠电流（TTX-s钠电流和TTX-R钠电流），可使两种钠电流的激活和失活曲线均向去极化方向移动，但对失活的影响大于对激活的影响，即延迟钠通道的失活过程；SO2 衍生物显著增大背根节神经元瞬间外向钾电流（Toca）和延迟整流钾电流（Ik），不影响TOCA的激活过程，但可使Ik的激活曲线向超极化方向移动，促进Ik的激活。另外，还可使TOCs的失活曲线向去极化方向移动，即延迟TOCa的失活。（3）SO：衍生物可显著增大大鼠心肌细胞L一型钙电流（Ica，L），使Ica.L的激活和失活曲线均向去极化方向移动，但对失活的影响大于对激活的影响；SO2衍生物显著增大心肌细胞钠电流，不影响钠通道的激活过程，但可使钠电流的失活曲线向去极化方向移动，延迟钠通道的失活过程；SO2衍生物显著增大心肌细胞瞬间外向钾电流（I50），使I50的激活曲线向超极化方向移动，促进I50的激活过程，但可使I50的失活曲线向去极化方向移动，延迟I50的失活过程；此外，SO2衍生物还可显著增大心肌细胞内向整流钾电流（IK），但不影响其反转电位。结果表明，SO：衍生物可能通过影响神经元和心肌细胞膜上离子通道的活动而对中枢神经、传导神经以及心血管系统产生不利影响。提示大气SO：污染可能与神经系统和心血管系统疾病的发生有关。

The oxygenation of endogenous cannabinoids (eCBs) 2-arachidonoyl glycerol (2-AG) and arachidonoyl ethanolamide by cyclooxygenase-2 (COX-2) produces novel types of prostanoids: prostaglandin glycerol esters (PG-Gs) and prostaglandin ethanolamides (PG-EAs). However, the physiological function of COX-2 oxidative metabolites of eCBs is still unclear. Here we demonstrate that PGE2-G, a COX-2 oxidative metabolite of 2-AG, induced a concentration-dependentincrease in the frequencyof miniature inhibitorypostsynaptic currents (mIPSCs) in primary cultured hippocampal neurons, an effect opposite to that of 2-AG. This increase was not inhibited by SR141716, a CB1 receptor antagonist, but was attenuated by an IP3 or MAPK inhibitor. In addition, we also examined the effects of other prostanoids derived from COX-2 oxygenation of eCBs on mIPSCs. PGD2-G, PGF2α-G and PGD2-EA, but not PGE2-EA or PGF2α-EA, also increased the frequency of mIPSCs. The eCB-derived prostanoid-induced responses appeared to be different from those of corresponding arachidonic acid-derived prostanoids, implying that these effects are not mediated via known prostanoid receptors. We further discovered that the inhibition ofCOX-2 activity reduced inhibitory synaptic activity and augmented depolarization-induced suppression of inhibition (DSI), whereas the enhancement of COX-2 augmented the synaptic transmission and abolished DSI. Our results, which show that COX-2 oxidative metabolites of eCBs exert opposite effects to their parent molecules on inhibitory synaptic transmission, suggest that alterations in COX-2 activity will have significant impact on endocannabinoid signalling in hippocampal synaptic activity.

The effects of the Xingou landfill leachate on levels of thiobarbituric acid reactive substances (TBARS) and the activities of Cu, Znsuperoxide dismutase (Cu, Zn-SOD), Se-dependent glutathione peroxidase (Se-dependent GPx) and catalase (CAT) were investigated in hearts, kidneys and spleens of Kunming albino mice of both sexes. Exposure to leachate caused significant increases of TBARS levels in the organs tested from mice of both sexes. For hearts, Cu, Zn-SOD, Se-dependent GPx and CAT activities were significantly increased at high concentrations for male mice, but the activities of these antioxidant enzymes were significantly increased at low concentration and decreased at high concentrations for female mice. For kidneys, Cu, Zn-SOD and Se-dependent GPx activities were significantly increased at high concentrations for male mice, but the activities were significantly increased at low concentrations and the ratio of increase was reduced with the increasing of concentration for female mice; CAT activities remained unchanged for male mice and were significantly increased at all concentrations tested for female mice. For spleens, Cu, Zn-SOD and Se-dependent GPx activities were significantly increased at high concentrations for male mice, but the activities were significantly increased at low concentrations and decreased at high concentrations for female mice; CAT activities remained unchanged for male mice and were significantly increased at high concentrations for female mice. The results suggest that leachate exposure can cause oxidative damage on hearts, kidneys and spleens of mice, and there were sex difference and organ difference in the response of antioxidant status.

The effects of the Xingou municipal landfill leachate on levels of thiobarbituric acid reactive substances (TBARS) and the activities of Cu,Zn-superoxide dismutase (Cu,Zn-SOD), Se-dependent glutathione peroxidase (Se-dependent GPx), and catalase (CAT) were investigated in brains and livers of Kunming albino mice of both sexes, using chemical oxygen demand (CODCr) as ameasure of leachate concentration. The results show that leachate caused lipid peroxidation and change of antioxidative status in brains and livers of mice. There was a sex difference in the response of antioxidative status, and female mice were more sensitive than male mice. Exposure to leachate at all concentrations tested caused significant increases of TBARS levels in brains and livers from mice of both sexes. For brains, Cu,Zn-SOD and Se-dependent GPx activities were significantly increased at high concentration (CODCr 240mg/L) for male mice, but the activities of both antioxidative enzymes were significantly increased at low concentration (CODCr 60mg/L) and decreased at high concentration (CODCr 240mg/L) for female mice; CAT activities remained unchanged for male mice and were significantly decreased for female mice at high concentration (CODCr 240mg/L). For livers, Cu,Zn-SOD and Se-dependent GPx activities were significantly increased at high concentrations (CODCr 120 and 240mg/L) for male mice, but the activities of both antioxidative enzymes were significantly increased at low concentration (CODCr 30 or 60mg/L) and decreased at high concentration (CODCr 240mg/L) for female mice; CAT activities were significantly increased for male mice at all concentrations tested and decreased for female mice at high concentrations (CODCr 120 and 240mg/L). These results suggest that leachate exposure can cause oxidative damage on brains and livers of mice. The results also suggest that leachate might induce toxicity in mammals by the free-radical-damage mechanism.

The cytogenetic damage induced by municipal landfill leachate was studied using chromosomal aberration (CA) in mouse bone marrow assay. Results show that leachate samples collected in different seasons decreased the mitotic index (MI), and caused significant increases of CA frequencies in treatment concentration (Chemical oxygen demand (COD) measured by the method of potassium dichromate oxidation, CODCr)-dependent manners. Compared with the negative control, reductions of the MI of 54 and 38% were detected for the highest leachate concentration (CODCr 320mg/L) in mouse bone marrow treated with both samples. The frequencies of CA increased significantly with increasing concentrations of sample 1 from CODCr 40 to 320mg/L, and from 80 to 320mg/L after exposure to sample 2. In addition, aseasonal difference of MI and CA frequencies induced by leachate was observed. The results confirm that leachate is a genotoxic agent in mammalian cells, and imply that exposure to leachate in aquatic environment may pose a potential genotoxic risk to mammals and humans. The results suggest that the CA in mouse bone marrow bioassay is efficient in genotoxicity studies of leachate on mammals, and that there appears to be a correlation between the genotoxicity in mammal system and the chemical measurement (CODCr) of leachate. The results also indicate that different discharge guidelines and environmental quality standards should be established for eachates discharged from landfills to aquatic environment in different seasons.