葡萄糖酸锌对矽肺大鼠脂质过氧化及抗氧化酶活性的影响

本文报告了葡萄糖酸锌，对矽肺大鼠预防性治疗和病后治疗脂质过氧化及抗氧化酶活性的影响。实验分为正常对照组、染尘对照组、葡萄糖酸锌１３ＬＤ５０治疗组和１５ＬＤ５０治疗组，疗程９０天。结果表明，治疗组大鼠血清过氧化脂质（ＬＰＯ）含量明显低于染尘对照组（Ｐ＜０．０５～０．００１），红细胞超氧化物岐化酶（ＳＯＤ）活性显著高于染尘对照组，以预防性治疗最明显。上述结果提示，葡萄糖酸锌有抑制或干扰石英引发的脂质过氧化反应的作用，同时本实验为进一步研究矽肺的抗氧化治疗提供了实验依据。     

抗矽口服液对大鼠实验性矽肺疗效观察

本文报告了抗矽口服液对大鼠实验性矽肺的治疗效果，结果表明，治疗组大鼠全肺湿重，干重，胶原蛋白和血清铜蓝蛋白（ＣＰ），过氧化脂质（ＬＰＯ），血清及每克肺（干重）的铜（Ｃｕ）含量均低于石英对照组，而红细胞超氧化物歧化酶（ＳＯＤ），血清及每克肺（干重）锌（Ｚｎ）含量则高于石英对照组，有显著性差异（Ｐ〈０．０５或Ｐ〈０．０１），肺纤维化程度治疗组多属Ｉ级或Ⅱ级，而石英对照组多属Ⅲ级或Ⅱ级～Ⅲ级。结果提示，     

汉防己甲素对矽肺大鼠肺中Ⅰ、Ⅲ型胶原基因表达的影响

使用Ｐｒｏα１（Ⅰ）、Ｐｒｏα１（Ⅲ）人胶原ｃＤＮＡ探针，采用ｃＤＮＡ－ｍＲＮＡ班点杂交技术，观察了染尘２个月、４个月的矽肺大鼠及汉防己甲素治疗１个月和３个月的矽肺大鼠肺组织中Ⅰ型、Ⅲ型胶原的ｍＲＮＡ水平的改变情况。实验结果表明，矽肺组织中Ⅰ、Ⅲ型胶原ｍＲＮＡ的含量比正常肺组织明显增加（Ｐ＜０．０５），汉防己甲素治疗后Ⅰ、Ⅲ型胶原正常含量则较矽肺组织显著减少。因此，我们认为矽肺病变组织中胶原纤维的积聚是由石英粉尘引起胶原基因表达改变所致；汉防己甲素能直接或间接地抑制胶原基因的转录，从而抑制矽肺病变中胶原蛋白的合成。     

SiO_2粉尘对大鼠肺组织与血清过氧化脂质水平的影响

目前对矽肺的发病机理,有种见解认为,SiO_2粉尘被吞噬细胞胞饮后发生分子水平的作用,是由于SiO_2催化脂质过氧化反应引起的。体外试验证明石英粉尘与豚鼠肺泡巨噬细胞在37℃下孵育1h,可使肺泡巨噬细胞的过氧化反应增强。对大鼠肺组织的脂质过氧化具有一定的剂量—效应关系,表现为双向性。而     

牛磺酸对染矽尘大鼠肺组织纤维化的防治作用

目的探讨牛磺酸对大鼠矽肺纤维化的影响及作用。方法实验大鼠随机分为对照组、模型组和牛磺酸治疗组,每组8只。检测各组大鼠血浆丙二醛(MDA)含量和超氧化物歧化酶(SOD)活力的变化,进行肺湿干重、肺系数测定及肺组织病理学检查。结果牛磺酸可显著降低染矽尘大鼠肺内MDA含量,抑制组织脂质过氧化的发生,提高SOD活力。牛磺酸治疗组大鼠肺湿干重、肺系数及病理学指标皆得到显著改善。结论牛磺酸对二氧化硅引起的大鼠矽肺纤维化有一定的防治作用。     

石英对大鼠血、肺和肺冲洗液中磷脂含量的影响

近年来,人们对脂质在矽肺发病中的作用引起广泛注意,石英微粒进入肺脏,引起矽肺病变,肺组织脂质代谢紊乱,磷脂含量增加,肺冲洗液磷脂含量也随着病变的发展而变化。本实验在观察石英对大鼠肺和肺冲洗液磷脂影响的同时,特别观察血磷脂含量的变化,并试用它作为判别氮氧喹哌和磷酸喹哌治疗大鼠矽肺效果的观察指标,借以探索磷脂在矽肺发病过程中的作用,为矽肺的实验研究和临床诊断提供依据。     

原油蒸气吸入引起大鼠肺脂质过氧化损伤的研究

给予大鼠吸入原油蒸气１５ｇ／ｍ３×８ｈ（急性染毒Ⅰ组）、３０ｇ／ｍ３×８ｈ（急性染毒Ⅱ组）、３ｇ／ｍ３×８ｈ／ｄ×３０ｄ（亚急性染毒组），观察血液和肺组织ＧＳＨ、ＭＤＡ含量和ＧＳＨ－Ｐｘ活性变化。结果３个染毒组大鼠血ＧＳＨ含量均明显减少；肺ＧＳＨ－Ｐｘ活性均有所下降，尤以２个急性染毒组酶活性下降显著（Ｐ＜０．０１），急性染毒Ⅱ组大鼠肺ＧＳＨ－Ｐｘ活性仅约为对照组的１／３；急性染毒Ⅱ组大鼠肺ＭＤＡ含量轻度增高，血ＭＤＡ含量显著增高（Ｐ＜０．０５）。本研究提示原油蒸气吸入，可削弱机体氧自由基清除系统的抗脂质过氧化损伤的活性，并引起一定程度的生物膜脂质过氧化损伤。表明脂质过氧化损伤反应可能是原油蒸气吸入引起肺损伤的机理之一。     

染石英及石棉尘大鼠肺灌洗液SDS-PAGE测定

目的探讨尘肺发病机理。方法采用ＳＤＳ－聚丙烯酰胺凝胶电泳（ＳＤＳ－ＰＡＧＥ）技术对染石英（２５ｍｇ／只）或石棉尘（５ｍｇ／只）大鼠支气管肺泡灌洗液（ＢＡＬＦ）进行了测定,并在光镜下观察天狼星红染色肺组织Ⅰ、Ⅲ型胶原分布情况。结果染石英不同时间大鼠ＢＡＬＦ中存在５条分子量分别为９０,６６,６０,２５,１４ＫＤ的蛋白质条带。染石棉大鼠ＢＡＬＦ仅有一条带,分子量为６６ＫＤ。染石英两周时,大鼠肺组织细胞纤维性结节中即有少量Ⅰ型胶原沉积,２个月时Ⅰ型胶原明显增加、粗大。石棉组３个月时肺间质中有Ⅰ型胶原存在。两组均未见明显Ⅲ型胶原。结论染石英大鼠ＢＡＬＦ中不同分子量蛋白质的出现可能对矽肺的发生有一定的促进作用     

青石棉染尘大鼠血,肺中SOD,LPO变化的研究

对大鼠经气管内注入青石棉纤维，在染尘后９０、１８０、２７０、３６０和５４０天动态观察血和肺中超氧化物歧化酶（ＳＯＤ）、脂质过氧化物（ＬＰＯ）及ＳＯＤ／ＬＰＯ比值的变化。结果表明，青石棉可诱发大鼠血和肺组织中自由基反应增强，ＳＯＤ活性降低，脂质过氧化反应增高，ＬＰＯ含量升高，抗氧化能力降低，ＳＯＤ／ＬＰＯ比值降低，体内抗氧化和脂质过氧化平衡失调。     

苯并（a）芘染毒大鼠血、肺中SOD、LPO及SOD／LPO变化的研究

用苯并（ａ）芘对大鼠经气管内染毒，在染毒后９０、１８０、２７０、３６０和５４０天时动态观察肺组织和血中超氧化物歧化酶（ＳＯＤ）、脂质过氧化物（ＬＰＯ）及ＳＯＤ／ＬＰＯ比值的变化．结果表明，苯并（ａ）芘可诱发大鼠血和肺组织中自由基反应增强，ＳＯＤ活性降低，脂质过氧化反应增高，ＬＰＯ含量升高，抗氧化能力降低，ＳＯＤ／ＬＰＯ比值降低．体内抗氧化和脂质过氧化平衡失调．     

21─氨基类固醇U─75412E对石英细胞毒性抑制作用的研究

观察了２１一氨基类固醇类药物Ｕ一７５４１２Ｅ对石英致肺巨噬细胞损伤的抑制作用。结果表明，Ｕ一７５４１２Ｅ具有很强的清除活性氧基团稳定细胞膜作用，显著降低了过氧化氢，乳酸脱氢酶和超氧化物歧化酶的释放。阻断了石英对肺泡巨噬细胞的损伤。     

Utilization and metabolism of [U-14C]4' galactosyllactose (O-beta-D-galactopyranosyl-(1----4)-O-beta-D-galactopyranosyl-(1----4)- D-glucopyranose) in rats

O-beta-D-Galactopyranosyl-(1----4)-O-beta-D-galactopyranosyl- (1----4)-D-glucopyranose (designated as 4'GL) are produced from lactose with Cryptococcus laurentii OKN-4. Excretion and metabolism of 4'GL in rats were examined using a radioisotope technique. [U-14c]4'GL was synthesized from [U-14C]lactose by Cryptococcus laurentii OKN-4. The 14CO2 in expired air was counted after oral administration of [U-14C]4'GL or [U-14C]lactose in conventional rats, rats treated with antibiotics and germ-free rats. The rate of 14CO2 excretion from conventional rats given [U-14C]4'GL was slower than that from those administered [U-14C]lactose. When [U-14C]4'GL was orally administered to rats given antibiotics, there was a 2-h delay in 14CO2 excretion, as compared to conventional rats. In germ-free rats, total excretion of 14CO2 from [U-14C]-4'GL decreased to about one-third of that of conventional rats during a 24-h period. Radioactivities in the serum, liver, and carcass of the [U-14C]4'GL oral administration group were lower than those of the [U-14C]lactose oral administration group. Radioactivities in the feces and urine however, were higher in [U-14C]4'GL group than in [U-14C]lactose group.     

姜黄素对人骨肉瘤细胞株/阿霉素多药耐药逆转作用的实验研究

目的观察姜黄素对多药耐受糖蛋白(P-gp)介导的人骨肉瘤细胞株/阿霉素(U-2OS/ADM)细胞多药耐药(MDR)的逆转作用。方法以阿霉素为诱导药物,人骨肉瘤细胞系U-2OS为诱导对象,采用大剂量冲击法建立人骨肉瘤多药耐药细胞系模型(U-2OS/ADM),采用MTT法检测姜黄素作用于U-2OS/ADM细胞前后对化疗药物的逆转;流式细胞仪检测细胞内罗丹明-123积聚和外排的影响。结果 MTT显示姜黄素20μmol/L能增加不同浓度阿霉素对U-2OS/ADM细胞的抑制作用(P<0.01),且姜黄素对阿霉素为2.0μg/ml时的U-2OS/ADM细胞抑制作用增加幅度达49%。FCM结果显示,姜黄素能增加阿霉素对U-2OS/ADM的细胞毒性作用,且呈剂量依赖关系。结论姜黄素可有效逆转U-2OS/ADM细胞的多药耐药现象的作用。     

Oxidation of dietary stearic, oleic, and linoleic acids in growing pigs follows a biphasic pattern

We used the pig as a model to assess the effects of dietary fat content and composition on nutrient oxidation and energy partitioning in positive energy balance. Pigs weighing 25 kg were assigned to either: 1) a low fat-high starch diet, or 2) a high saturated-fat diet, or 3) a high unsaturated-fat diet. In the high-fat treatments, 20% starch was iso-energetically replaced by 10.8% lard or 10.2% soybean oil, respectively. For 7 d, pigs were fed twice daily at a rate of 1200 kJ digestible energy · kg(-0.75) · d(-1). Oral bolus doses of [U-(13)C] glucose, [U-(13)C] α-linoleate, [U-(13)C] stearate, and [U-(13)C] oleate were administered on d 1, 2, 4, and 6, respectively, and (13)CO(2) production was measured. Protein and fat deposition were measured for 7 d. Fractional oxidation of fatty acids from the low-fat diet was lower than from the high-fat diets. Within diets, the saturated [U-(13)C] stearate was oxidized less than the unsaturated [U-(13)C] oleate and [U-(13)C] linoleate. For the high unsaturated-fat diet, oxidation of [U-(13)C] oleate was higher than that of [U-(13)C] linoleate. In general, recovery of (13)CO(2) from labeled fatty acids rose within 2 h after ingestion but peaked around the next meal. This peak was induced by an increased energy expenditure that was likely related to increased eating activity. In conclusion, oxidation of dietary fatty acids in growing pigs depends on the inclusion level and composition of dietary fat. Moreover, our data suggest that the most recently ingested fatty acids are preferred substrates for oxidation when the direct supply of dietary nutrients has decreased and ATP requirements increase.     

Food intake in baboons: effects of a long-acting cholecystokinin analog

Food intake of four adult male baboons (Papio c. anubis) was monitored during daily experimental sessions lasting 22h. Food was available under a two-component operant schedule. Following completion of the first "procurement component" response requirement, access to food, i.e. a meal, became available under the second "consumption component" during which each response produced a 1-g food pellet. After a 10-min interval in which no response occurred, the consumption component was terminated. A long-acting cholecystokinin (CCK) analog U-67827E (U-67: 0.80-3.2 micrograms/kg) was administered, in the thigh muscle, at 1100 hrs immediately prior to the start of the daily session on Tuesdays and Fridays. U-67 significantly reduced intake during the first 8-h of the session, and intake during the entire 22-h session. The decreased intake was due to a significant decrease in the size of the first meal of the session as a consequence of decreased duration of feeding without a change in response rate. U-67 also produced dose-dependent increases in latency to the first meal of up to 2.5 h. These results demonstrate that a long-acting CCK analog decreases food intake over a prolonged period of time in a naturalistic feeding situation. In addition, the effects of U-67 were limited to the consumption component, suggesting that this CCK analog affected food intake by interacting with physiological mechanisms specifically associated with feeding.     

Functional alterations of alveolar macrophages subjected to smoke exposure and antioxidant lazaroids.

Acute inhalation of diesel fuel-polycarbonate plastic (DFPP) smoke causes severe lung injury, leading to acute respiratory distress syndrome (ARDS) and death. It has been reported that the initiation of acute lung injury is associated with the activation of pulmonary alveolar macrophages (PAM). To further explore the pathogenesis, alveolar macrophages (AM) of New Zealand rabbits ventilated and exposed to a 60 tidal volume of DFPP smoke in vivo were recovered at 1 h post-smoke. Smoke exposure induced significant increases in both mRNA and protein levels for PAM tumor necrosis factor-alpha (TNF-alpha), when compared to smoke control. Smoke also induced a biphasic response (inhibited at 2 h, enhanced at 24 h after cell isolation) in the production of superoxide (O2-) by PAM. However, aerosolized lazaroid, U75412E (1.6 mg/kg body weight), significantly attenuated smoke-induced expression in AM TNF-alpha at the protein level but not at the mRNA level, and smoke-induced changes in AM production of O2-. This study suggests that highly expressing AM TNF-alpha following smoke may be a key contributor to the cascade that establishes an acute injury process and exacerbates oxidant-derived cell injury. Whereas, the lazaroid may ameliorate smoke-induced lung injury by attenuating AM TNF-alpha release, in addition to its primary antioxidative mechanism.     

Attachment reaction of rat uterine luminal epithelium V. Suppression of the attachment reaction by some antifertility agents

The effects of the postcoitally active antifertility agents U-11,555A, U-11,100A, MER-25, ICI-46,474, 66/179, F-6103, F-6255, F-6278 and ORF-4563 on the ultrastructure of the rat uterine luminal epithelium were studied in spayed, virgin rats under three experimental conditions.

1. Expt. I. When given separately, all agents gave an estrogen-like response. This was most marked with the F-compounds and ORF-4563.

2. Expt. II. In progesterone-treated rats, the F-compounds and ORF-4563 changed the ultrastructure profoundly, while the other compounds had little effect.

3. Expt.III. A combination of progesterone and estradiol renders the epithelium suitable for implantation; a parallel change in the ultrastructure is the attachment reaction.

When given before estradiol, each compound except U-11,555A inhibited the attachment reaction in most animals.

In conclusion, the F-compounds and ORF-4563 had strong estrogenic effects in all tests. Their antifertility activity is probably related to this property. The other substances were almost indistinguishable from estradiol in Expt. I but did not induce an attachment reaction in Expt. II as estradiol does. In Expt. III these substances, except U-11,555A, seemed to act like anti-estrogens, interfering with the attachment-inducing effect of estradiol, which may explain their antifertility activity. How U-11,555A exerts its antifertility activity is not clear.     

Induction of tumor necrosis factor-alpha by cefodizime in U-937 cells

Cefodizime has modulating effects on the release of diverse cytokines. We determined the modulator activity of this antibiotic on the production of TNF in human monocytic U-937 cells. The measurement of TNF was carried out by ELISA test and by a L-929 cells-based citotoxic bioassay. The results showed that cefodizime alone induced the production of TNF on U-937 cells, however, the addition of LPS led to a decrease in the release of this cytokine (p < 0.05). On the other hand, the combination of cefodizime-PMA had a synergic effect (p < 0.05), while addition of LPS to this combination caused a decrease of TNF production (p < 0.05). With these results we conclude that cefodizime modulates the production of TNF in U-937 cells, which is down regulated by the addition of LPS.     

Induction of Cell Cycle Arrest and Apoptosis in Human Osteosarcoma U-2 OS Cells by Solanum lyratum Extracts

This research focused on a Chinese herb medicine, Solanum lyratum Thunb (Solanaceae) by ethanol extracts (SLE) for investigating the molecular anticancer mechanism in vitro for exploring the means of cell death through the effects on mitochondrial function. We found that SLE induced cytotoxic effects in human osteosacroma U-2 OS cells, and these effects include cell morphological changes, a decrease of the percentage of viable cells and induction of apoptosis. The results suggest that cell death induced by SLE is closely related to apoptosis based on the observations of DAPI staining and sub-G1 phase in U-2 OS cells. Flow cytometric assays also showed that SLE promoted the production of reactive oxygen species and nitric oxide but decreased the levels of mitochondrial membrane potential and promoted the activations of caspase-8 and -9 in U-2 OS cells. SLE inhibited the level of Bcl-2 but promoted the Bax level, and both proteins led to the release of cytochrome c from mitochondria to cytosol and activation of caspase-9 and -3, resulting in the apoptotic death which is mediated through the mitochondrial pathway. Taken together, SLE was demonstrated to be effective in killing U-2 OS osteosacroma cells via the ROS-promoted and mitochondria- and caspase-dependent apoptotic pathways.     

The synthesized novel fluorinated compound (LJJ-10) induces death receptor- and mitochondria-dependent apoptotic cell death in the human osteogenic sarcoma U-2 OS cells

We designed the 6-fluoro-2-(3-fluorophenyl)-4-substituted anilinoquinazoline derivatives as less toxic anti-cancer candidates. Our result demonstrated that LJJ-10 has greater cytotoxicity than that of the other compounds in human osteogenic sarcoma U-2 OS cells. LJJ-10-induced apoptosis was associated with enhancing ROS generation, DNA damage, and an increase of the protein levels of Fas, FasL, FADD, caspase-8, cytochrome c, Apaf-1, AIF, Endo G, caspase-9 and caspase-3 in U-2 OS cells. LJJ-10-triggered growth inhibition was significantly attenuated by N-acetylcysteine, cyclosporine A, anti-FasL monoclonal antibody, and caspase-8, -9 and -3 specific inhibitors in U-2 OS cells. We suggest that LJJ-10-induced apoptotic cell death in U-2 OS cells through death receptor- and mitochondria-dependent apoptotic signaling pathways.