目的探讨在三七皂苷(panax notoginseng saponins,Pn S)Rg1干预下,肝纤维化大鼠线粒体质子跨膜转运的变化和肝线粒体膜的流动性的变化,为开发三七单体Rg1在临床抗纤维化的应用提供详尽的试验依据和理论基础。方法 72只Wistar大鼠随机分...目的探讨在三七皂苷(panax notoginseng saponins,Pn S)Rg1干预下,肝纤维化大鼠线粒体质子跨膜转运的变化和肝线粒体膜的流动性的变化,为开发三七单体Rg1在临床抗纤维化的应用提供详尽的试验依据和理论基础。方法 72只Wistar大鼠随机分为对照组、四氯化碳(carbon tetrachloride,CCl4)肝纤维化大鼠模型组、Pn S Rg1组各24只。除对照组外,其余2组用5%CCl4橄榄油按5 m L/kg灌胃制作肝纤维化大鼠模型。Pn S Rg1组在每次CCl4灌胃同时腹腔注射Pn S Rg1(5 mg/kg)用稳态荧光探针标记技术动态观察肝纤维化大鼠线粒体质子跨膜转运的变化,用荧光偏振法测定肝线粒体膜的流动性和膜的微黏度的改变。结果 (1)与对照组相比,肝纤维化模型组大鼠用单因素多组间方差分析,发现模型组大鼠质子跨膜转运中,肝线粒体质子跨膜转运能力显著下降(P<0.01)。Pn S Rg1组与对照组相比质子跨膜转运的变化没有显著性意义(P>0.05),与模型组相比,有显著性差异(P<0.01)。(2)肝纤维化模型组大鼠用单因素多组间方差分析,与对照组相比,证实模型组大鼠线粒体膜的流动性显著下降(P<0.01),增加膜的微黏度(P<0.01);而Rg1组与模型组相比增加线粒体膜的流动性(P<0.01),降低膜的微黏度(P<0.01)。结论肝纤维化大鼠肝线粒体质子跨膜转运能力下降和线粒体膜的流动性显著下降是导致肝纤维化的重要原因之一。Pn S Rg1通过增加肝线粒体质子跨膜转运能力和线粒体膜的流动性而防治肝纤维化的发生发展的。展开更多
This study examined the impact of 935MHz phone-simulating electromagnetic radiation on embryo implantation of pregnant mice.Each 7-week-old Kunming (KM) female white mouse was set up with a KM male mouse in a single c...This study examined the impact of 935MHz phone-simulating electromagnetic radiation on embryo implantation of pregnant mice.Each 7-week-old Kunming (KM) female white mouse was set up with a KM male mouse in a single cage for mating overnight after induction of ovulation.In the first three days of pregnancy,the pregnant mice was exposed to electromagnetic radiation at low-intensity (150 μW/cm2,ranging from 130 to 200 μW/cm2,for 2-or 4-h exposure every day),mid-intensity (570 μW/cm2,ranging from 400 to 700 μW/cm2,for 2-or 4-h exposure every day) or high-intensity (1400 μW/cm2,ranging from 1200 to 1500 μW/cm2,for 2-or 4-h exposure every day),respectively.On the day 4 after gestation (known as the window of murine embryo implantation),the endometrium was collected and the suspension of endometrial glandular cells was made.Laser scanning microscopy was employed to detect the mitochondrial membrane potential and intracellular calcium ion concentration.In high-intensity,2-and 4-h groups,mitochondrial membrane potential of endometrial glandular cells was significantly lower than that in the normal control group (P<0.05).The calcium ion concentration was increased in low-intensity 2-h group but decreased in high-intensity 4-h group as compared with the normal control group (P<0.05).However,no significant difference was found in mitochondrial membrane potential of endometrial glandular cells between low-or mid-intensity groups and the normal control group,indicating stronger intensity of the electromagnetic radiation and longer length of the radiation are required to inflict a remarkable functional and structural damage to mitochondrial membrane.Our data demonstrated that electromagnetic radiation with a 935-MHz phone for 4 h conspicuously decreased mitochondrial membrane potential and lowered the calcium ion concentration of endometrial glandular cells.It is suggested that high-intensity electromagnetic radiation is very likely to induce the death of embryonic cells and decrease the chance of their implantation,thereby posing a high risk to pregnancy.展开更多
This study aimed to observe the effects of tyroserleutide (tyrosyl-seryl-leucine, YSL) on the growth of human hepatocarcinoma BEL-7402 that was transplanted into nude mice, and explore its anti-tumor mechanism prelimi...This study aimed to observe the effects of tyroserleutide (tyrosyl-seryl-leucine, YSL) on the growth of human hepatocarcinoma BEL-7402 that was transplanted into nude mice, and explore its anti-tumor mechanism preliminarily. YSL, at doses of 80 μg·kg?1·d?1, 160 μg·kg?1·d?1 and 320 μg·kg?1·d?1 significantly inhibited the growth of the human hepatocarcinoma BEL-7402 tumor in nude mice, producing inhibition of 21.66%, 41.34%, and 34.78%, respectively. Ultra structure of BEL-7402 tumor in nude mice showed that YSL could induce tumor cells apoptosis and necrosis, cell organelle mitochondria and endoplasmic reticulum damage, and calcium over-load. By confocal laser scanning microscopy and flow cytometry, we found that 10 μg/mL YSL rapidly induced an increase of the concentration of cytoplasmic free calcium in BEL-7402 cells in vitro, and maintained high concentrations of cytoplasmic free calcium for 1 h. Then the calcium concentration began to decrease after 2 h, and was lower than that of the control group at 4 h and 24 h (p<0.05). YSL also decreased the mitochondrial transmembrane potential of BEL-7402 cells in vitro, but had no effect on the calcium homeostasis or mitochondrial transmembrane potential of Chang liver hepatocytes. So affecting calcium homeostasis, then inducing apoptosis and necrosis may be a mechanism by which YSL inhibits the tumor growth in animal model.展开更多
文摘目的探讨在三七皂苷(panax notoginseng saponins,Pn S)Rg1干预下,肝纤维化大鼠线粒体质子跨膜转运的变化和肝线粒体膜的流动性的变化,为开发三七单体Rg1在临床抗纤维化的应用提供详尽的试验依据和理论基础。方法 72只Wistar大鼠随机分为对照组、四氯化碳(carbon tetrachloride,CCl4)肝纤维化大鼠模型组、Pn S Rg1组各24只。除对照组外,其余2组用5%CCl4橄榄油按5 m L/kg灌胃制作肝纤维化大鼠模型。Pn S Rg1组在每次CCl4灌胃同时腹腔注射Pn S Rg1(5 mg/kg)用稳态荧光探针标记技术动态观察肝纤维化大鼠线粒体质子跨膜转运的变化,用荧光偏振法测定肝线粒体膜的流动性和膜的微黏度的改变。结果 (1)与对照组相比,肝纤维化模型组大鼠用单因素多组间方差分析,发现模型组大鼠质子跨膜转运中,肝线粒体质子跨膜转运能力显著下降(P<0.01)。Pn S Rg1组与对照组相比质子跨膜转运的变化没有显著性意义(P>0.05),与模型组相比,有显著性差异(P<0.01)。(2)肝纤维化模型组大鼠用单因素多组间方差分析,与对照组相比,证实模型组大鼠线粒体膜的流动性显著下降(P<0.01),增加膜的微黏度(P<0.01);而Rg1组与模型组相比增加线粒体膜的流动性(P<0.01),降低膜的微黏度(P<0.01)。结论肝纤维化大鼠肝线粒体质子跨膜转运能力下降和线粒体膜的流动性显著下降是导致肝纤维化的重要原因之一。Pn S Rg1通过增加肝线粒体质子跨膜转运能力和线粒体膜的流动性而防治肝纤维化的发生发展的。
基金supported by the National Natural Science Foundation of China (No.30670509)
文摘This study examined the impact of 935MHz phone-simulating electromagnetic radiation on embryo implantation of pregnant mice.Each 7-week-old Kunming (KM) female white mouse was set up with a KM male mouse in a single cage for mating overnight after induction of ovulation.In the first three days of pregnancy,the pregnant mice was exposed to electromagnetic radiation at low-intensity (150 μW/cm2,ranging from 130 to 200 μW/cm2,for 2-or 4-h exposure every day),mid-intensity (570 μW/cm2,ranging from 400 to 700 μW/cm2,for 2-or 4-h exposure every day) or high-intensity (1400 μW/cm2,ranging from 1200 to 1500 μW/cm2,for 2-or 4-h exposure every day),respectively.On the day 4 after gestation (known as the window of murine embryo implantation),the endometrium was collected and the suspension of endometrial glandular cells was made.Laser scanning microscopy was employed to detect the mitochondrial membrane potential and intracellular calcium ion concentration.In high-intensity,2-and 4-h groups,mitochondrial membrane potential of endometrial glandular cells was significantly lower than that in the normal control group (P<0.05).The calcium ion concentration was increased in low-intensity 2-h group but decreased in high-intensity 4-h group as compared with the normal control group (P<0.05).However,no significant difference was found in mitochondrial membrane potential of endometrial glandular cells between low-or mid-intensity groups and the normal control group,indicating stronger intensity of the electromagnetic radiation and longer length of the radiation are required to inflict a remarkable functional and structural damage to mitochondrial membrane.Our data demonstrated that electromagnetic radiation with a 935-MHz phone for 4 h conspicuously decreased mitochondrial membrane potential and lowered the calcium ion concentration of endometrial glandular cells.It is suggested that high-intensity electromagnetic radiation is very likely to induce the death of embryonic cells and decrease the chance of their implantation,thereby posing a high risk to pregnancy.
基金This study was supported by the“863”Project(Grant No.2004AA2Z3170)from the Nat ional Important Project Grant(Grant No.03007)from the Ministry of Education of ChinaPre-Explore of Key Basic Science Program of Ministry of Science and Technology ofChina(Grant No.2003CCA04300).
文摘This study aimed to observe the effects of tyroserleutide (tyrosyl-seryl-leucine, YSL) on the growth of human hepatocarcinoma BEL-7402 that was transplanted into nude mice, and explore its anti-tumor mechanism preliminarily. YSL, at doses of 80 μg·kg?1·d?1, 160 μg·kg?1·d?1 and 320 μg·kg?1·d?1 significantly inhibited the growth of the human hepatocarcinoma BEL-7402 tumor in nude mice, producing inhibition of 21.66%, 41.34%, and 34.78%, respectively. Ultra structure of BEL-7402 tumor in nude mice showed that YSL could induce tumor cells apoptosis and necrosis, cell organelle mitochondria and endoplasmic reticulum damage, and calcium over-load. By confocal laser scanning microscopy and flow cytometry, we found that 10 μg/mL YSL rapidly induced an increase of the concentration of cytoplasmic free calcium in BEL-7402 cells in vitro, and maintained high concentrations of cytoplasmic free calcium for 1 h. Then the calcium concentration began to decrease after 2 h, and was lower than that of the control group at 4 h and 24 h (p<0.05). YSL also decreased the mitochondrial transmembrane potential of BEL-7402 cells in vitro, but had no effect on the calcium homeostasis or mitochondrial transmembrane potential of Chang liver hepatocytes. So affecting calcium homeostasis, then inducing apoptosis and necrosis may be a mechanism by which YSL inhibits the tumor growth in animal model.