氯霉素对大鼠胚胎发育的影响

本研究用大鼠致畸试验探讨了氯霉素对胚胎发育的影响。Wistar大鼠90只,体重290±SD12g,随机分5组,雌、雄2:1同笼阴道涂片见到精子定为妊娠0天。氯霉素的剂量为10、20、40和160mg/kg。于妊娠7～11天腹腔注射染毒,对照组给等容量的二甲     

棕榈氯霉素的合成工艺改进

棕榈氯霉素（ｃｈｌｏｒａｍｐｈｅｎｉｃｏｌｐａｌｍｉｔａｔｅ,１）是由氯霉素（２）与棕榈酰氯（３）在吡啶作用下合成。作者在实验中发现其文献报道［１～３］的提纯工艺复杂,１的质量难以达到英国药典对２及棕榈酸（４）的要求,为此进行了工艺改进。利用２与棕榈酸铵盐溶于热水及１不溶的性质,通过热分层方法除去粗品１中的２及４;同时在酯化反应中使用３粗品,并以三乙胺代替吡啶。实验部分棕榈酰氯（３）于反应瓶中加入４（２５．６ｇ,０．１ｍｏｌ）、苯（２５ｍｌ）及氯化亚砜（２４ｇ,０．２ｍｏｌ）。回流反应５ｈ后,减…     

抵抗素及其结合多肽对大鼠肝细胞糖原合成的影响

目的 探讨抵抗素(resistin)及其结合多肽(RBP)对大鼠肝细胞糖原合成的影响.方法 体外培养大鼠BRL肝细胞,分为空白对照组、抵抗素(60 ng/ml)干预组、RBP(1 nmol/L)干预组和抵抗素(60 ng/ml) RBP(1 nmol/L)联合干预组,培养2 h后筹集细胞,以蒽酮法检测胞内糖原含量,并采用RT-PCR法检测TRS2、SOCS3、GLUT2等基因mRNA的表达变化.结果 与空白对照组比较,抵抗素干预组糖原含量显著下降,但RBP干预组则无显著差异;与抵抗素干预组相比,抵抗素 RBP联合干预组糖原含量明显升高.各干预组BRL细胞中GLUT2基因的mRNA水平无显著差异.抵抗索干预组SOCS3 mRNA水平显著上调、IRS2 mRNA水平显著下凋;但两者在抵抗素 RBP联合下预组则尤明显变化.结论 RBP能拮抗抵抗素抑制肝细胞糖原合成的作用,但对正常肝细胞糖原合成功能无明显影响.     

异丙酚对脓毒症大鼠肝细胞凋亡的影响

目的：探讨异丙酚对脓毒症大鼠肝细胞凋亡及肝功能的影响。方法：Wistar大鼠30只随机分为假手术组、对照组和异丙酚组，每组10只，其中对照组和异丙酚组采用盲肠结扎穿刺术（CLP）致脓毒症模型，检测肝细胞凋亡的情况，并测定丙氨酸氨基转移酶（ALT）和乳酸脱氢酶（LDH）的水平，假手术组麻醉后不行CLP术，其余同实验组。结果：对照组、异丙酚组肝细胞凋亡指数较假手术组均明显增加（P〈0．01），但异丙酚组肝细胞凋亡指数较对照组显著降低（P〈0．01）。结论：异丙酚具有抑制脓毒症大鼠肝细胞凋亡的作用，对脓毒症大鼠肝细胞具有一定的保护作用。     

氯霉素对小白鼠血象的影响

氯霉素作为第一个广谱抗生素自1947年起曾广泛应用于临床,但因其毒性(引起再障)而限制其应用,然而某些临床资料说明氯霉素虽然可造成骨髓损害,但停药后大多数可恢复。本文采用小白鼠口服氯霉素观察对末梢血液有形成分生成的抑制作用,现将结果报告如下。 1 资料与方法小白鼠10只,鼠龄40～60d,雌雄兼有,体重20g。盐酸氯霉素(齐齐哈尔第二制药厂制品)。将小鼠随机编号、称重,开始采用灌胃给药的方法(药物浓度     

二甲基甲酰胺对大鼠肝细胞钙稳态的影响

二甲基甲酰胺(DMF)是一种用途广泛的有机溶剂,文献报道,DMF为亲肝性毒性,其作用详细机理尚未阐明。为探讨DMF对肝细胞钙稳态的影响及其与肝细胞损伤的关系,我们选用磷酸化酶a作为肝细胞浆钙离子浓度的间接指标,测定DMF与原代培养的大鼠肝细胞孵育一定时间后胞浆磷酸化酶a活性,同时测定GPT、GOT漏出量,并用台盼蓝拒染法观察细胞生长状况。     

低剂量的硒与镉联合作用对大鼠肝细胞DNA损伤的影响

目的 研究低剂量的亚硒酸钠和氯化镉联合作用对离体大鼠肝细胞DNA损伤的影响。方法 在2．185、4．375和8．750μmol／L的剂量条件下，亚硒酸钠和氯化镉联合作用，用单细胞凝胶电泳检测大鼠肝细胞DNA损伤。结果 2．185μmol／L的亚硒酸钠对2．185μmol／L的氯化镉引起的DNA损伤拮抗作用不明显，但有拮抗作用的趋势；4．375μmol／L亚硒酸钠对4．375μmol／L氯化镉引起的DNA损伤有明显的拈抗作用；而在8．750μmol／L的剂量下，亚硒酸钠与氯化镉存在相互拈抗的关系。结论 在硒和镉对大鼠肝细胞DNA损伤的联合作用中，较低剂量的亚硒酸钠对氯化镉没有拮抗作用，而在一定的剂量条件下，亚硒酸钠和氯化镉存在着相互拮抗的关系。     

肝细胞生长因子对四氯化碳损伤原代培养大鼠肝细胞的保护作用

采用大鼠离体肝细胞原代培养24 h，并利用CCl₄造成急性肝细胞损伤模型，检定肝细胞生长因子(HGF)对肝细胞损伤的影响. 结果表明：HGF可显著降低中毒肝细胞及细胞膜脂质过氧化物水平, 抑制肝细胞脂质过氧化, 并降低谷丙转氨酶和谷草转氨酶水平, 稳定质膜；显著促进中毒肝细胞RNA和DNA的合成；超微病理证实HGF能减轻CCl₄对肝细胞质膜，染色质, 线粒体, 内质网及核蛋白体的损害.     

肝细胞生长因子对四氯化碳损伤原代培养大鼠肝细胞的保护作用

采用大鼠离体肝细胞原代培养２４ｈ，并利用ＣＣｌ４造成急性肝细胞损伤模型，检定肝细胞生长因子（ＨＧＦ）对肝细胞损伤的影响．结果表明：ＨＧＦ可显著降低中毒肝细胞及细胞膜脂质过氧化物水平，抑制肝细胞脂质过氧化，并降低谷丙转氨酶和谷草转氨酶水平，稳定质膜；显著促进中毒肝细胞ＲＮＡ和ＤＮＡ的合成；超微病理证实ＨＧＦ能减轻ＣＣｌ４对肝细胞质膜，染色质，线粒体，内质网及核蛋白体的损害     

Effect of clofibrate on DNA synthesis in rat liver and kidney

A single dose of clofibrate (400 mg/kg), given to rats, increased the incorporation of (^3H)thymidine into liver DNA, in a period of 20–30 h after administration. However, (^3H)thymidine incorporation into hepatic DNA of rats treated repeatedly was identical to that of control animals. After the administration of a single dose of clofibrate a small increase in (^3H)thymidine incorporation also occurred in kidney DNA; repeated doses, however, resulted in a marked suppression of labeling.Dedicated to Professor Dr. med. Herbert Remmer on the occasion of his 65th birthday     

T细胞在小鼠脊髓损伤与修复中的作用

目的 研究T细胞在小鼠脊髓损伤(SCI)与修复中的作用.方法 用BALB/C-NU小鼠(N组)、BALB/C-NU同胞小鼠(H组)、ICR小鼠(I组)建立不完全SCI模型,每组21只.术前、术后1、3、7、14、28、42、56d行脊髓运动功能(BBB)评分,免疫组化染色检测损伤区脊髓CD3、CD68和神经生长因子(NGF)表达.结果 H、I组在术后各时间点BBB评分均低于N组(P＜0.05或P＜0.01);除术后14d,H组和I组间BBB评分差异无统计学意义(P＞0.05).SCI后,各组CD3、CD68和NGF阳性细胞表达均上调;其中,H、I组CD3、NGF表达明显高于N组(P＜0.01).结论早期T细胞对SCI可能有损伤作用,而后期可能有促进修复作用.     

卡维地洛对血管平滑肌细胞DNA合成的影响

目的 :探讨卡维地洛对血管平滑肌细胞(VSMC)增殖的影响及其可能机制。方法 :通过贴壁细胞培养法建立豚鼠主动脉血管平滑肌细胞模型 ,应用 [3 H]TDR掺入试验研究卡维地洛对反应性氧族 (reactiveoxygenspecies ,ROS)、血管紧张肽Ⅱ(angiotensinⅡ ,AngⅡ )及胎牛血清 (fetalcalfserum ,FCS)诱导的血管平滑肌细胞增殖的影响。结果 :卡维地洛呈剂量依赖性地抑制ROS ,AngⅡ及FCS诱导的血管平滑肌细胞DNA合成 ,最大抑制率分别为 (48± 15 ) % ,(42± 7) %和 (44± 14) %。结论 :卡维地洛对ROS及AngⅡ诱导的血管平滑肌细胞DNA合成呈剂量相关性的抑制作用 ,提示卡维地洛可能通过抗氧化的途径抑制血管平滑肌细胞增殖     

Decreased cisplatin damage-dependent DNA synthesis in cellular extracts of mismatch repair deficient cells

The proficiency of both nucleotide excision repair (NER) and DNA mismatch repair (MMR) influences cellular sensitivity to cisplatin (cis-diamminedichloroplatinum). To gain further insight into how MMR may influence platinum drug sensitivity, the effect of loss of MMR on repair synthesis was measured in vitro by a commonly used method that relies on whole-cell extracts to drive [alpha-32P]dATP incorporation into cisplatin-damaged plasmid DNA. Extracts evaluated include those from cells with or without functional hMLH1 (HCT116+ch2 versus HCT116+ch3, respectively) and hMSH2 (HEC59 versus HEC59+ch2, respectively). Loss of MMR in the HCT116 system was associated with a 2.8-fold reduction in cisplatin damage-specific DNA synthesis, whereas it was associated with a 3.0-fold reduction in the HEC59 system, suggesting that a decrease in the ability to repair cisplatin-damaged DNA accompanies loss of MMR. An in vitro DNA excision assay that utilized a substrate containing a site-specific cisplatin adduct was performed. Using this highly NER-specific assay, no significant difference was apparent between the extracts derived from NER-proficient versus -deficient cells. These and other data lead us to suggest that the increase in apparent repair synthesis in platinum-damaged plasmids by extracts from MMR-proficient versus -deficient cellular extracts may reflect a distinct and possibly adverse DNA synthetic process rather than productive NER.     

Enhanced liver DNA synthesis in partially hepatectomized rats pretreated with 2,3,7,8-tetrachlorodibenzo-p-dioxin

The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on liver DNA synthesis was studied in rats after a $\text{1}\text{3}$ hepatectomy. The rats were maintained on a controlled feeding schedule and were treated with 5 μg/kg of TCDD or acetone/corn oil (control). Five days after treatment a $\text{1}\text{3}$ hepatectomy was performed and at designated times thereafter liver DNA synthesis was measured by [³H]thymidine incorporation into DNA. The main finding was that liver DNA synthesis was increased 8- to 10-fold by TCDD over that which was observed in control rats. This increase occurred after a latency period that was appropriate for the regenerative liver DNA synthesis response. Other experiments showed that increased incorporation of thymidine in TCDD-treated rats could be blocked by hydroxyurea, an inhibitor of semiconservative DNA synthesis, and that the increased incorporation was secondary to increased DNA synthesis and not increased thymidine kinase activity. Thus, hepatocytes in TCDD-treated rats respond in a quantitatively different manner than control rats to the same proliferative signal, $\text{1}\text{3}$ hepatectomy. Liver DNA synthesis in nonhepatectomized TCDD-treated rats tended to be greater than control, but the difference was not statistically significant.     

Effect of various iron chelating agents on DNA synthesis in human cells

A number of hydroxamic acid derivatives, including salicyl-, octano-, decano- and dodecanohydroxamic acid and rhodotorulic acid, inhibited ³H-thymidine incorporation into DNA, lowered the concentration of dATP and raised the concentration of dTTP in human PHA-stimulated lymphocytes. These effects suggest that these compounds, like desferrioxamine, inhibit ribonucleotide reductase, an iron-requiring enzyme. On the other hand, benzoic acid derivatives did not inhibit ribonucleotide reductase assessed by the dATP and dTTP pool changes, although some did inhibit DNA synthesis judged by ³H-thymidine incorporation into DNA. A number of other compounds known to chelate iron also inhibited DNA synthesis without inhibiting ribonucleotide reductase. These results suggest that different iron binding compounds affect different iron pools in the cell and that some of them may have use as cytotoxic agents.     

Effect of anticonvulsants on in vitro prothrombin synthesis in adult and fetal rat liver

Prothrombin synthesis in a postmitochondrial supernatant fraction of rat liver from vitamin K-deficient rats was unchanged in the presence of 10^?3m concentrations of phenobarbital, phenytoin, or primidone. Warfarin (10^?5m) significantly decreased prothrombin synthesis with 4.4 X 10^?7 or 2.2 × 10^?6m vitamin K added to the incubation medium whereas phenytoin (10^?3m) had no affect. Pretreatment of vitamin K-deficient adult male rats for 2 days with phenobarbital (80 mg/kg), phenytoin (200 mg/kg), or primidone (200 mg/kg) did not alter in vitro prothrombin synthesis. Pregnant vitamin K-deficient rats were treated from the 14th to 20th day of gestation with 100 mg/kg phenytoin or 80 mg/kg phenobarbital. Although the fetuses contained significant quantities of phenytoin (95.4 ± 37.5 μg/ml serum) or phenobarbital (32.25 ± 4.51 μg/ml serum), prothrombin synthesis by fetal liver was unaffected. Feeding a diet deficient in both vitamin K and folic acid to pregnant rats treated with phenytoin (100 mg/kg) also did not alter prothrombin synthesis but appeared to increase fetal accumulation of phenytoin (289 ± 109.9 μg/ml serum).