姜黄素在荷瘤小鼠体内各组织的分布及药物动力学研究

目的研究姜黄素在荷HAC肿瘤小鼠体内各组织的分布及其药物动力学。方法给荷HAC肿瘤小鼠尾静脉注射姜黄素注射液(100mg/kg),分别在注射20,40,100min后取小鼠的肝、肾、肺、心、瘤块和腹水等组织抽提姜黄素,并用高效液相色谱法测定含量。结果给药后20min,测得荷HAC肿瘤小鼠肝、肾、肺、心、瘤块和腹水等组织内姜黄素含量分别为6.40,0.98,0.13,0.06,0.05,0.02μg/g;40min时,测得肝、肾、肺内含量分别为0.20,0.06,0.02μg/g,而其他组织未测得姜黄素;100min时,仅在肝脏测得0.04μg/g。结论姜黄素在荷HAC肿瘤小鼠体内的分布主要集中于肝脏,而病灶内含量很低,体内代谢均很快。     

Protective effect of triterpenoid fractions from the rhizomes of Astilbe chinensis on cyclophosphamide-induced toxicity in tumor-bearing mice

Aim of the study

The objectives of this study were to investigate the protective effect of the triterpenoid fractions from the rhizomes of Astilbe chinensis (Saxifragaceae) (ATF) on cyclophosphamide (CTX)-induced toxicity in tumor-bearing mice.

Materials and methods

The mice inoculated with mouse sarcoma S180 cells were treated with saline or CTX alone, or co-treated with CTX and ATF. The blood, femur bone, and serum samples were collected for determination of the haematological and biochemical parameters and splenocytes were for assay of proliferation, the activity of natural killer (NK) cells, and production of interleukin-2 (IL-2).

Results

ATF significantly increased the peripheral white blood cell (WBC) count and bone marrow cellularity (BMC) in CTX-treated S180-bearing mice. Increase of aspartate transanimase (AST), alanine transaminase (ALT), urea nitrogen (BUN), and creatinine in the serum of CTX-treated mice was significantly reversed by ATF. The lowered levels of splenocytes proliferation, NK cells activity, and IL-2 production from splenocytes in S180-bearing mice after CTX treatment were also increased by ATF administration.

Conclusions

ATF provides significant protection against CTX-induced hematotoxicity, hepatotoxicity, nephrotoxicity, and immunotoxicity, and might be helpful in abrogation of CTX-induced toxicity during the chemotherapy.     

中九食道康颗粒对荷瘤小鼠免疫功能的影响

目的研究中药制剂中九食道康颗粒对荷瘤小鼠免疫功能的影响。方法建立荷瘤小鼠模型,将小鼠随机分组:①正常对照组;②模型组;③中九食道康颗粒高、中、低剂量组;④环磷酰胺组。观察计算廓清指数、血清溶血素水平、胸腺指数和脾脏指数。结果中九食道康颗粒可增加荷瘤小鼠的网状内皮系统吞噬功能,使血清溶血素生成值升高;对荷瘤小鼠免疫器官重量的影响不显著。结论中九食道康颗粒具有提高体液免疫功能的作用。     

吴茱萸碱对肺癌荷瘤小鼠生长及HIF-1α/VEGF信号通路的影响

目的：探讨吴茱萸碱对Lewis肺癌荷瘤小鼠肿瘤生长及缺氧诱导因子-1α/血管内皮生长因子（HIF-1α/VEGF）信号通路的影响。方法：通过皮下注射Lewis肺癌细胞建立荷瘤小鼠模型,建模后分为模型对照组、阳性对照组（顺铂干预）及吴茱萸碱低、高剂量组,共干预14 d。通过检测各组小鼠造模给药期间肿瘤大小,计算抑瘤率,评价吴茱萸碱对肺癌荷瘤小鼠肿瘤生长的影响。此外,运用定量PCR（qPCR）法检测吴茱萸碱干预14 d后各组小鼠肿瘤组织中HIF-1α及VEGF mRNA表达的影响,免疫组织化学染色评估肿瘤组织中HIF-1α、VEGF及血小板-内皮细胞黏附分子（CD31）表达水平,计算肿瘤组织中微血管密度（MVD）。结果：吴茱萸碱对肺癌荷瘤小鼠肿瘤生长具有显著的抑制作用,阳性对照组及吴茱萸碱低、高剂量抑瘤率分别为53.13%、20.49%、38.54%;吴茱萸碱各给药剂量组可不同程度下调Lewis肺癌荷瘤小鼠肿瘤组织HIF-1α及VEGF基因及蛋白表达（P<0.01）,减少肿瘤组织中MVD（P<0.01）。结论：吴茱萸碱可抑制肺癌荷瘤小鼠肿瘤生长,其作用机制可能是通过减少肿瘤组织中HIF-1α及VEGF表达,抑制肿瘤中血管生成。     

胸廓外持续负压对健康犬血流动力学及呼吸力学的影响

目的　比较胸廓外持续负压(CNEP)和呼气末正压(PEEP)对健康犬血流动力学和呼吸力学的影响。方法　通过实验犬股静脉插入SwanGanz漂浮导管,监测不同通气状态下血流动力学,并记录呼吸力学指标。结果　CNEP与PEEP比较,前者对血流动力学和呼吸力学指标均无明显影响,同时对尿量也无影响。而PEEP不仅影响血流动力学和呼吸力学指标,还使尿量明显减少。结论　CNEP联合间歇正压通气(IPPV)不会对血流动力学和呼吸力学产生不利影响,因此在某些病理状态下可考虑选择CNEP。     

Disposition of conjugate-bound and free doxorubicin in tumor-bearing mice following administration of a BR96-doxorubicin immunoconjugate (BMS 182248)

Purpose: The chimeric BR96–doxorubicin (DOX) immunoconjugate, BMS 182248, has induced remissions and cures of human lung adenocarcinoma (L2987) implanted in athymic mice. The purpose of this study was to evaluate the biodistribution of DOX after BMS 182248 administration to tumor-bearing mice and to evaluate the ability of BMS 182248 to target DOX to tumors. Methods: For this evaluation, L2987-implanted mice were given BMS 182248 (5 mg DOX/kg; three doses 4 days apart) and the levels of both conjugate-bound and free DOX in plasma, tumor, liver and heart were determined. Results: Conjugate-bound DOX comprised the majority of plasma DOX, with relatively low levels of free DOX present. From plasma, conjugate-bound DOX distributed to the tissues examined with the order of concentration (per gram of tissue) being tumor > liver > heart. Free DOX was also detected in liver and heart, but at concentrations lower than those present after an equivalent DOX dose (5 mg/kg; three doses 4 days apart). The total exposure of heart to free DOX after BMS 182248 administration was about one- quarter of that found after the administration of DOX alone. The elimination kinetics of both conjugate-bound and free DOX from heart and liver after BMS 182248 administration paralleled those observed from plasma, indicating that equilibrium had been attained between these nontumor tissues and plasma. The elimination kinetics of both entities from tumors, however, were different from those from plasma, liver and heart. BMS 182248 produced sustained levels of both conjugate-bound and free DOX which were present throughout the experiment. This suggested that, in contrast to normal tissues, tumor tissue retention of BMS 182248 by antigen-promoted binding had occurred and that the kinetics of free DOX in the tumors were controlled by the rate of release of DOX from tumor-associated BMS 182248. As a result of this retention, the tumor concentrations of free DOX after BMS 182248 administration exceeded those produced by i.v. administration of DOX at the same dose, a finding consistent with the greater antitumor activity of BMS 182248 relative to DOX. BMS 182248 also liberated DOX upon incubation with rat liver lysosomes and was accumulated by L2987 cells in culture, with the subsequent intracellular release of DOX. Conclusions: BMS 182248 effectively delivered DOX to L2987 xenografts implanted in athymic mice and produced higher and more prolonged tumor concentrations of free DOX than the administration of DOX alone. Following BMS 182248 administration, normal tissues (liver and heart) were exposed to lower overall concentrations of free DOX than were produced by administration of an equivalent DOX dose. Received: 18 June 1996 / Accepted: 27 November 1996     

Tumor-associated Expression of a Serum Protein, Termed αX Protein (α-Inhibitor III), and Its mRNA in Rat Liver

A cDNA clone bearing the mRNA sequence for rat αX protein (αX) was isolated from a cDNA library constructed from rat liver mRNA. The nucleotide sequence of αX protein cDNA showed 97% homology with that of the 3' -proximal domain of α₁-inhibitor III cDNA. The amino acid sequence deduced from that of αX cDNA also exhibited high homology with the primary sequences of α₁-inhibitor III and α₂-macroglobulin. K231 ascites hepatoma cells were transplanted into male ACI rats, and the level of αX mRNA in the liver of the tumor-bearing rats was determined by RNA blot hybridization with the cDNA probe. The serum concentration of αX decreased to about 30% of the control value with time after transplantation. The amount of αX mRNA in the liver of tumor-bearing rats was proportional to the serum concentration of αX. The serum concentrations of transferrin and albumin in the tumor-bearing rats also decreased to about 30 and 60% of the normal levels, respectively. However, the amounts of mRNAs for transferrin and albumin in the liver of tumor-bearing rats did not decrease. These findings indicate that the mechanisms of tumor-associated decrease in the concentrations of different serum proteins In tumor-bearing rats may differ.     

Enhanced adriamycin—induced delayed gastrointestinal radiosensitivity in tumor-bearing mice

Intestinal proliferative activity in BDF, mice bearing the Lewis lung tumor (LL_ca/BDF₁) was markedly depressed with increasing tumor burden. When compared with non-tumor-bearing mice (BDF₁), integrated cell production over 7 days was reduced to 56% in animals with small (400 mm³) tumors and to 30% in animals with large (2500 mm³) tumors. Gastrointestinal radiosensitivity was measured by proliferative compensatory response kinetics to a radiation dose of 600 rad. The presence of tumor (mean tumor volume = 859 ± 209 mm³) delayed the jejunal response to radiation by 24 hr and reduced the integrated cell production from 136% in BDF₁ mice to 119% in the LL_ca/BDF₁ mice. While the presence of tumor did not alter the temporal response of the colonic epithelium to radiation, the compensatory peak was reduced from 248% (BDF₁) to 200% (LL_ca/BDF₁). Adriamycin (Adr; 10 mg/kg) given 60 days prior to radiation failed to enhance the jejunal radiosensitivity in BDF₁ mice. However, when tumor-bearing LL_ca/BDF₁ mice were treated under an identical dose and time configuration, the jejunal response to 600 rad was significantly impaired: proliferative peaks were reduced from 182 to 115% ; integrated cell production was reduced from 119 to 72%. In the colon of tumor-bearing mice, pretreatment with AdR reduced the proliferative compensatory peak from the subsequent radiation dose to 120% of pretreatment levels.     

灵芝多糖联合低剂量顺铂抑瘤作用及对荷瘤鼠免疫功能的影响

目的研究灵芝多糖与顺铂联合用药对荷瘤小鼠的肿瘤生长情况及其免疫功能的影响。方法Balb／c小鼠腋下接种小鼠肺癌细胞株Lewis5×10^6个细胞,待肿瘤至100min^3分组给药。分为对照组、灵芝多糖组（1次／2d,40mg／kg,灌胃）、顺铂组（1次／2d,2mg／kg,腹腔注射）和联合用药组（等剂量的顺铂和灵芝多糖）。每3天测量一次肿瘤的体积,30d后解剖,检测荷瘤小鼠的肿瘤大小、脾脏的变化,脾脏和外周血中免疫细胞的变化以及相关免疫细胞的功能。结果灵芝多糖可有效增加小剂量顺铂的抗肿瘤效果,提高荷瘤小鼠的存活率,使小鼠外周血中Th细胞向Thl转化,增加细胞免疫功能,并增加骨髓来源DC细胞表面CDllc分子的表达（与对照组比较灵芝多糖组从1．06％升至4．59％,与顺铂比较,联合用药组从2．8％升至7．21％）,提高抗原提呈能力。结论灵芝多糖可以提高荷瘤小鼠的免疫功能,与小剂量顺铂联合用药后,具有协同抗肿瘤生长作用,且可提高小鼠存活率。     

黑蒜水提液对小鼠肝癌H22移植性实体瘤的生长干预

目的:探讨黑蒜水提液对人肝癌SMMC 7721细胞及小鼠肝癌Hep.A22移植性实体瘤生长的作用。方法:体外培养SMMC 7721细胞,观察黑蒜水提液干预后对细胞增殖的影响;将昆明小鼠移植H22肝癌细胞后,分阴性对照组,环磷酰胺组,黑蒜水提液低、中、高剂量组,联合加热治疗组6个组,计算黑蒜水提液对肝癌实体瘤的抑瘤率、胸腺指数和脾指数;对小鼠血清细胞因子IL-2含量测定。结果:黑蒜水提液对肝癌肿瘤均有明显的抑制生长作用,抑瘤有效率可大于40%。结论:通过确定黑蒜水提液作为纯中药抗肿瘤药物的抑瘤作用,为临床应用提供实验依据。