Effect of high volume hemofiltration on CHOP protein from a canine model of multiple organ dysfunction syndrome

Objective To observe the effect of high volume hemofiltration (HVHF) on the expression of CCAAT enhancer binding protein(CHOP) during the treatment of multiple organ dysfunction syndrome (MODS). To investigate the role of CHOP protein act in apoptosis pathway mediated by the endoplasmic reticulum stress. Methods Twelve Beagle dogs were subjected to hemorrhagic shock plus resuscltation and endotixemia to establish MODS model, then they were randomly divided into two groups: HVHF group (n=6) and MODS group (n=6). After endotoxin injection completed, the HVHF group received HVHF treatment for 24 hours; MODS group did not receive. Vivo experiments: Blood samples were obtained at different time points(before operation, 0 h, 6 h, 12 h, 24 h after the injection of endotoxin). The dogs were killed and the tissue samples from lung, liver and kidney were took, then the expression of CHOP mRNA was determined. Vitro experiments: human umbilical vein endothelial cells (HUVECs) were induced by two groups’ blood samples to establish the apoptosis model. Gene expression, protein quantification and cell apoptosis rate were determined before and after the interference. Results Vivo experiments: The levels of CHOP mRNA from lung, liver and kidney had no significant difference between the two groups (P＞0.05). Vitro experiments: (1)The expression of CHOP mRNA: Compared with MODS group, the expression levels of CHOP mRNA were significantly decreased in HVHF group at 6 h, 24 h after the injection of endotoxin (P＜0.05). Compared with before, the expression levels of CHOP mRNA in the two groups were both significantly decreased after CHOP siRNA interference (P＜0.05). (2)The expression of CHOP protein: Compared with MODS group, the expression levels of CHOP protein were significantly decreased in HVHF group at each time points (P＜0.05). Compared with before, the expression levels of CHOP protein in the two groups were both significantly decreased after CHOP siRNA interference(P＜0.05). (3)Endothelial cell apoptosis rate: Compared with the preoperative rate, the two group’s endothelial cell apoptosis rate was decreased significantly at each time points(P＜0.05). Compared with MODS group, the endothelial cell apoptosis rate was significantly decreased in HVHF group at each time points(P＜0.05). Compared with before, the endothelial cell apoptosis rate in the two groups was both significantly decreased after CHOP siRNA interference(P＜0.05). Conclusion In the treatment of MODS process, HVHF can reduce endothelial cell apoptosis which may be related to the inhibition of CHOP mRNA expression and protein synthesis.     

氯化锂对小鼠体细胞遗传毒性作用的实验研究

观察氯化锂的遗传毒性特征并对其毒作用机制做一初步探讨。以氯化锂为受试物,昆明种小鼠为受试对象,分低（２２．５ｍｇ／ｋｇ）、中（７５．０ｍｇ／ｋｇ）、高（２２５．０ｍｇ／ｋｇ）３个不同剂量组进行小鼠体细胞遗传毒性试验。氯化锂经口灌胃染毒后,小鼠骨髓细胞染色体畸变率增高（Ｐ〈０．０５）;骨髓细胞微核率、胎肝细胞微核率增高（Ｐ〈０．０５,Ｐ〈０．０１）。结果表明,一定剂量的氯化锂对昆明种小鼠体细胞具有遗     

氯化锂对小鼠的遗传毒性研究

目的：观察氯化锂对小鼠体细胞及生殖细胞的遗传毒性特征对其毒作用机制做一初步探讨,方法以氯化锂为受试物,昆明种小鼠为受试对象,进行小鼠体细胞和生殖细胞遗传毒性试验。结果 氯化锂经口灌胃染毒后,小鼠骨髓细胞染色体畸变率增加（Ｐ〈０．０５）;骨髓细胞微核率,胎肝细胞微核率增高（Ｐ〈０．０５,Ｐ〈０．０１）。小鼠睾丸细胞染色体畸变率增加（Ｐ〈０．０５）;着床前胚泡细胞微核率增加（Ｐ〈０．０１）。结论：一定     

烟酰胺对长波紫外线照射黑素细胞黑素合成的干预

目的研究烟酰胺对长波紫外线（UVA）致人皮肤黑素细胞黑素合成的干预作用。方法观察0．2J／cm^2 UVA（365nm）照射人皮肤黑素细胞后，烟酰胺在不同剂量时对人皮肤黑素细胞中黑素合成和转运的干预作用。结果0．2J／cm^2 UVA照射后，黑素细胞中黑素含量明显增加，UVA照射后的人皮肤黑素细胞给予不同剂量的烟酰胺时，黑素细胞中黑素含量明显下降，10．0mmol／ml时作用更为明显。烟酰胺在有效抑制黑素含量的同时，对黑素细胞的细胞周期、细胞凋亡及DNA指数无明显影响；0．2J／cm^2 UVA照射后立即给予烟酰胺时，烟酰胺可以调节黑素细胞中mRNA的表达水平。结论烟酰胺能够拮抗UVA的致黑作用；10．0mmol／ml烟酰胺在干预UVA所致的黑素细胞致黑作用的同时，对黑素细胞的作用浓度是安全的；烟酰胺参与其中黑素的转运；鉴于烟酰胺拮抗UVA致黑作用的有效结果，烟酰胺有望用于防护UVA照射所引起的晒黑作用。     

烟酰胺对长波紫外线致人皮肤黑素细胞增殖的干预作用

目的研究烟酰胺对长波紫外线(UVA)致人皮肤黑素细胞增殖的干预作用。方法观察UVA(365nm)0.2cm2照射人皮肤黑素细胞后立即和照射后48h给予不同剂量烟酰胺后的细胞增殖率、细胞内钙离子浓度和Na+-K+、Ca2+-ATP酶活力。结果UVA照射黑素细胞后给予1.000mg/ml烟酰胺,24h即出现抑制黑素细胞增殖的作用,至48h时作用更为明显,自0.125mg/ml组就出现明显的抑制作用;烟酰胺1.25mg/ml可使黑素细胞内钙离子浓度增高;0.250mg/ml可使黑素细胞内Na+-K+、Ca2+-ATP酶活力增高,差异有统计学意义(P<0.05)。经UVA照射后立即给予不同浓度烟酰胺时,细胞内钙离子浓度和Na+-K+、Ca2+-ATP酶活力差异均无统计学意义(P>0.05)。结论UVA照射黑素细胞后即给予烟酰胺对经UVA照射后的保护作用较照射后经过一段时间再给予的作用效果明显。通过影响Ca2+及细胞内钙泵的活性很可能是烟酰胺干预黑素细胞增殖的途径之一。