绿舒筋总生物碱对人肝癌细胞抑制作用

目的:研究绿舒筋对体外培养肝癌细胞株的抑制效应.方法:采用乳酸脱氢酶释放法测定绿舒筋、5-Fu、环磷酰胺对体外培养肝癌细胞株的毒性作用.结果:绿舒筋具有抑制肿瘤生长作用,并随药物浓度增加其效应增强,其效应类似于5-Fu和环磷酰胺.结论:绿舒筋具有较好的抗肿瘤细胞生长作用,可望成为临床抗癌药物.     

2型糖尿病患者血清瘦素与脂肪肝的相关性研究

目 的 探讨２型 糖 尿病 患者 血 清瘦 素水 平 与脂 肪 肝、脂 代谢 、性 别、体 重指 数 （ＢＭ Ｉ）及胰 岛 素 抵 抗的相 关 性。 方法 随机 选取１０８例２型糖 尿 病患 者根 据 是否 合并 脂 肪肝 分 为 糖 尿病 合 并 脂 肪 肝组 （ＤＦＬ）和糖 尿 病无 脂肪 肝 组 （ＤＮＦ），测 量 身 高 、体 重 、空 腹 血 清 胆 固 醇 （ＴＣ）、甘 油 三 酯 （ＴＧ ）、高 密 度 脂 蛋 白 （Ｈ ＤＬ）、低 密 度 脂 蛋 白（ＬＤＬ）、载 脂 蛋白Ａ （ＡｐｏＡ ）、载 脂蛋 白Ｂ（ＡｐｏＢ）和 空 腹血 糖 （ＦＰＧ ）、真胰 岛 素 （ＦＴＩ）、瘦 素 （ＬＥＰ）及 馒 头 餐后 ２ ｈ真 胰岛 素 （ＰＴＩ），以 胰 岛素 敏 感 指 数（ＩＳＩ）＝１／（ＦＰＧ ×ＦＴＩ）作 为 胰 岛 素 敏 感 指 数 ，对 瘦 素 与 脂 肪 肝 、ＢＭ Ｉ、及 糖 脂 代 谢 指 标及胰 岛 素敏 感 指数 做相 关 性分 析。 结 果 ①糖 尿 病 合并 脂 肪 肝 的发 病 率 为４３．６％ ；② ＤＦＬ组 的瘦 素 、体重 指 数 和血脂 水 平高 于ＤＮ Ｆ组 ，胰 岛素 敏 感指 数ＤＦＬ组低 于ＤＮ Ｆ组 ；③ Ｄ ＦＬ组和ＤＮ Ｆ组女 性瘦 素 均明 显高 于 男性 ；④多元 素线性 回 归表 明瘦 素 与性 别、体重 指 数、空 腹 胰岛 ?     

Characteristic expression profiles induced by genotoxic carcinogens in rat liver.

When applied in toxicological studies, the recently developed gene expression profiling techniques using microarrays, which brought forth the new field of toxicogenomics, facilitate the interpretation of a toxic compound's mechanism of action. In this study, we investigated whether genotoxic carcinogens at doses known to induce liver tumors in the 2-year rat bioassay deregulate a common set of genes in a short-term in vivo study and, if so, whether these deregulated genes represent defined biological pathways. Rats were dosed with the four genotoxic hepatocarcinogens dimethylnitrosamine (4 mg/kg/day), 2-nitrofluorene (44 mg/kg/day), aflatoxin B1 (0.24 mg/kg/day), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK, 20 mg/kg/day). After treatment for up to 14 days, the expression profiles of the livers were analyzed on Affymetrix RG_U34A microarrays. Among the significantly upregulated genes were a set of target genes of the tumor suppressor protein p53, indicating a DNA damage response. Such a response was expected and, therefore, confirmed the validity of our approach. In addition, the gene expression changes suggest a specific detoxification response, the activation of proliferative and survival signaling pathways, and some cell structural changes. These responses were strong throughout the 14 day time course for 2-nitrofluorene and aflatoxin B1; in the case of dimethylnitrosamine and NNK, the effects were weakly detectable at day 1 and then increased with time. For dimethylnitrosamine and aflatoxin B1, which caused observable inflammation in vivo, we found a corresponding upregulation of inflammatory genes at the same time points. Thus, by the toxicogenomic analysis of short-term in vivo studies, we identified genes and pathways commonly deregulated by genotoxic carcinogens, which may be indicative for the early events in tumorigenesis and, thus, predictive of later tumor development.     

Neoplastic and preneoplastic lesions induced by melamine in rat urothelium are modulated by dietary polyunsaturated fatty acids

The modulatory effects of polyunsaturated fatty acids (PUFA) on urinary tract tumorigenesis of 275 Wistar rats were evaluated by treating animals with the tumorigenic agent melamine. Rats were fed with formulae containing 6% of 4 varieties of fats: fish oil enriched in n-3 PUFA (FO), corn oil enriched in n-6 (CO), olein containing mainly n-9 oleic acid (O), and 98% stearic acid (SA), the latter two being essential (EFA)-deficient inducers. Two commercially fed control groups with (CM) and without (C) melamine were used. Animals were autopsied at 22–25 and at 36–40 weeks. Hepatic fatty acids showed that O and SA groups were EFA-deficient. Simple well differentiated hyperplasias were significantly higher in the FO lot, whereas dysplasia was increased in the CO, O and SA lots. Most of the animals fed for 36–40 weeks with the three latter formulae developed the more severe lesions. Increased urothelial proliferation was more frequent in EFA-deficient rats. The apoptosis/mitosis ratio was higher in O, SA and CO fed animals with respect to FO and chow ones. Results show that dietary PUFA modulate differentially both normal and pre-neoplastic urothelial proliferation induced by melamine. FO, rich in n-3 fatty acids, showed a strong protective effect.     

凉血解毒、滋肾柔肝法治疗慢性肝炎肝纤维化40例临床观察

目的:研究中药对慢性肝炎肝纤维化的治疗作用.方法:治疗组(40例)予以凉血解毒、滋肾柔肝中药治疗,对照组(30例)予以澳泰乐冲剂和大黄虫丸,疗程6个月,观察肝纤维化指标的变化情况.结果:治疗组病人经治疗后血清透明质酸(HA)、层粘蛋白(LM)、Ⅳ型胶原肽(C-Ⅳ)及Ⅲ型前胶原肽(PⅢP)均明显降低,与对照组比较,有显著性差异(P《0.05).结论:凉血解毒、滋肾柔肝法是治疗慢性肝炎肝纤维化的重要法则,所选方药是临床治疗慢性肝炎肝纤维化的有效药物.     

龙眼参对小鼠化学性肝损伤的保护作用及其机制研究

目的 :研究龙眼参对小鼠化学性肝损伤的保护作用及其机制。方法 :分别对四氯化碳、硫代乙酰胺和对乙酰氨基酚所致小鼠化学性肝损伤模型进行分组对照实验 ,并对各项相关指标进行测定和比较。结果 :与模型组比较 ,龙眼参治疗组ALT活性明显降低 ;肝脏细胞色素P450 及细胞色素b5 含量升高 ;肝组织丙二醛的含量显著降低 ;苯胺羟化酶及氨基比林 -N -去甲基酶活性增强 ;肝微粒体Ca2 + -ATP酶的活性明显降低 ;谷胱甘肽及谷胱甘肽过氧化物酶的水平明显提高。结论 :龙眼参对小鼠化学性肝损伤具有保护作用 ,其机制可能与其抗氧自由基、抑制脂质过氧化、诱导肝药酶活性和阻滞Ca2 +通道的作用有关。     

沙苑子黄酮对DMN诱导的大鼠肝纤维化形成的影响

目的　观察沙苑子黄酮对二甲基亚硝胺 (DMN)诱导的大鼠肝纤维化形成的影响。方法　采用DMN诱导大鼠肝纤维化 ,期间给予灌服沙苑子黄酮 (30 ,6 0 ,12 0mg·kg-1) ,设秋水仙碱组作对照 ,给药 4wk后 ,测定血清谷丙氨转氨酶(ALT)、谷草转氨酶 (AST)活性、总蛋白 (TP)和白蛋白 (Alb)含量 ,放射免疫分析法测定血清透明质酸 (HA)、层粘连蛋白(LN)含量。光镜和电镜观察肝细胞结构和肝纤维化程度。结果　沙苑子黄酮预防给药 ,明显降低DMN诱导肝纤维化大鼠血清ALT、AST活性 (P <0 0 1,P <0 0 1) ,提高血清TP和Alb含量 (P <0 0 5 ,P <0 0 1) ,降低血清HA和LN含量 (P <0 0 1)。病理学观察结果 ,沙苑子黄酮预防组大鼠胶原纤维沉积明显减轻 ,假小叶结构明显减少 ,电镜观察显示 ,沙苑子黄酮组肝细胞结构接近正常 ,disse间隙、肝细胞内胶原纤维明显减少。结论　沙苑子黄酮预防给药 ,可抑制DMN诱导的大鼠肝纤维化形成     

奥曲肽对肝癌细胞SMMC-7721增殖的抑制作用

目的 :探讨奥曲肽抑制肝癌细胞生长的作用。方法 :人肝癌细胞SMMC 772 1培养于含 10 %胎牛血清、10 0U·ml-1青霉素、链霉素的RPMI16 40培养液中。以 4个稀释度 10 -5、10 -4、10 -3 、10 -2 g·L-1将奥曲肽加入培养液 ,于加药后第 4 8h行MTT比色实验检测生长抑制率。奥曲肽浓度为 10 -3 g·L-1时于0、6、12、2 4、36h行DNA染色分析细胞周期。结果 :MTT比色法测定显示奥曲肽抑制肝癌细胞的生长 ,在浓度为 10 -5、10 -4、10 -3 、10 -2 g·L-1作用 4 8h生长抑制率分别为 9.33%、 12 .70 %、 19.70 %、2 0 .93%。药物作用 12、2 4h ,G0 -G1期细胞比例增加 ,G2 -M期细胞比例减少。结论 :奥曲肽抑制体外培养的人肝癌细胞的增殖 ,机制可能是将肝癌细胞阻滞于G0 -G1期 ,阻止细胞进入G2 -M期。     

奥利司他对肥胖IGT人群糖尿病预防效果

目的 探讨奥利司他(Orlistat,赛尼可)对肥胖糖耐量低减(IGT)患者的干预效果。方法 患者随机分两组奥利司他治疗组(50例)和对照组(51例),治疗为期1年,于治疗前后测量血脂、口服糖耐量试验(OGTT)、体重、身高等指标。结果1年后,治疗组上述指标明显改善(P<0.01),其恶化为糖尿病的发病率明显低于对照组(P<0.01)。结论 在肥胖IGT干预治疗中,奥利司他加饮食和运动治疗后可使体重减轻,改善糖耐量,明显减少糖尿病的发生。     

Organ slice viability extended for pathway characterization: an in vitro model to investigate fibrosis.

Liver slice viability is extended to 96 h for rat, expanding the use of this in vitro model for studying mechanisms of injury and repair, including pathways of fibrosis. The contributing factors to increased organ slice survival consist of the use of a preservation solution for liver perfusion and slice preparation, obtaining rats that are within the weight range of 250-325 g, placing a cellulose filter atop the titanium mesh roller-insert to support the slice, and maintaining the slices in an optimized culture medium which is replaced daily. The liver slices remain metabolically active, synthesizing adenosine triphosphate (ATP), glutathione, and glycogen, and exhibit preserved organelle integrity and slice morphology. Slice preparation results in 2-cut surfaces which likely triggers a repair and regenerative response. The fibrogenic pathways are evident by the activation of stellate cells, the proliferation of myofibroblast-like cells, and an increased collagen deposition by 48 h. Markers indicative of activated stellate cells, alpha-smooth muscle actin, collagen 1a1, desmin, and HSP47 are substantiated by real time-PCR. Increased staining of alpha-smooth muscle actin initially around the vessels and by 72-96 h in the tissue is accompanied by increased collagen staining. Microarray gene expression revealed extracellular matrix changes with the up-regulation of cytoskeleton, filaments, collagens, and actin genes; and the down-regulation of genes linked with lipid metabolism. The improvements in extending liver slice survival, in conjunction with its three-dimensional multi-cellular complexity, increases the application of this in vitro model for investigating pathways of injury and repair, and fibrosis.