Background Hepatocellular carcinoma （HCC） ranked the second among the causes of cancer mortality in China since the 1990s. Up to now, medication still plays an important role in the treatment of HCC. The therapies b...Background Hepatocellular carcinoma （HCC） ranked the second among the causes of cancer mortality in China since the 1990s. Up to now, medication still plays an important role in the treatment of HCC. The therapies based on the allicin as a potential chemopreventive analog although is in its infancy at the present time, may have a significant role in the future management of HCC. Diallyl trisulfide （DATS） is a natural compound derived from garlic. In this study, we investigated the inhibitory effects of hepatic targeted polybutylcyanoacrylate nanoparticles of diallyl trisulfide （DATS-PBCA-NP） on orthotopic transplanted HepG2 hepatocellular carcinoma in nude mice. Methods DATS-PBCA-NP were detected by transmission electron microscope （TEM） and high-performance liquid chromatography （HPLC）. The orthotopic transplantation HCC models were established by implanting HCC HepG2 xenograft bits under the envelope of the mice liver. Successful models （n=29） were divided into 4 groups： normal saline （NS）, empty nanoparticles （EN）, DATS and DATS-PBCA-NP were intravenously administered to the mice respectively for 2 weeks. In vivo antitumor efficacy was evaluated by the measurement of tumor volume. Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling （TUNEL） assay and protein levels of apoptosis and cell proliferation proteins by immunoblotting in tumor tissues were performed to elucidate the possible mechanism. Results DATS-PBCA-NP possessed smooth and round appearance, dispersed well, and released in vitro in accord with double phase kinetics model. DATS-PBCA-NP changed the tissue/organ distribution of DATS in vivo. The successful rate of tumor implantation was 100%. Intravenous administration of DATS-PBCA-NP significantly retarded the growth of orthotopically transplanted hepatoma in BALB/c nude mice （compared with the other three groups, all P〈0.05） without causing weight loss （P〉0.05）. TUNEL staining showed that the tumors from DATS-PBCA-NP treated mice exh展开更多
基金a fund of the Natural Science Foundation of Shandong(No.Y2004C34)
文摘Background Hepatocellular carcinoma （HCC） ranked the second among the causes of cancer mortality in China since the 1990s. Up to now, medication still plays an important role in the treatment of HCC. The therapies based on the allicin as a potential chemopreventive analog although is in its infancy at the present time, may have a significant role in the future management of HCC. Diallyl trisulfide （DATS） is a natural compound derived from garlic. In this study, we investigated the inhibitory effects of hepatic targeted polybutylcyanoacrylate nanoparticles of diallyl trisulfide （DATS-PBCA-NP） on orthotopic transplanted HepG2 hepatocellular carcinoma in nude mice. Methods DATS-PBCA-NP were detected by transmission electron microscope （TEM） and high-performance liquid chromatography （HPLC）. The orthotopic transplantation HCC models were established by implanting HCC HepG2 xenograft bits under the envelope of the mice liver. Successful models （n=29） were divided into 4 groups： normal saline （NS）, empty nanoparticles （EN）, DATS and DATS-PBCA-NP were intravenously administered to the mice respectively for 2 weeks. In vivo antitumor efficacy was evaluated by the measurement of tumor volume. Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling （TUNEL） assay and protein levels of apoptosis and cell proliferation proteins by immunoblotting in tumor tissues were performed to elucidate the possible mechanism. Results DATS-PBCA-NP possessed smooth and round appearance, dispersed well, and released in vitro in accord with double phase kinetics model. DATS-PBCA-NP changed the tissue/organ distribution of DATS in vivo. The successful rate of tumor implantation was 100%. Intravenous administration of DATS-PBCA-NP significantly retarded the growth of orthotopically transplanted hepatoma in BALB/c nude mice （compared with the other three groups, all P〈0.05） without causing weight loss （P〉0.05）. TUNEL staining showed that the tumors from DATS-PBCA-NP treated mice exh
文摘目的建立稳定的改良小鼠脑死亡模型,分享脑死亡建模和维护经验。方法 C57BL/6小鼠随机数字表法分为脑死亡组(n=25)和假手术组(n=10),颅内插入2F Fogarty球囊导管并应用缓慢持续颅内加压法建立小鼠脑死亡模型,经口腔气管插管机械通气和颈静脉补液维持脑死亡状态,颈动脉插管监测心率和平均动脉压,假手术组插入球囊导管但不加压,光镜下观察供肝组织学改变(HE染色)。结果颅内加压20 min后成功诱导小鼠脑死亡,对应的球囊内平均液体量为(105.77±21.57)μl。濒临脑死亡期间平均动脉压和心率迅速升高达峰值后逐渐降低,峰值分别为(128.28±17.16)mm Hg(1 mm Hg=0.133 k Pa)和(434.16±55.75)次/min,均显著高于对应点的假手术对照组(均P=0.000)。在4 h的观察期内,72%(18/25)的小鼠平均动脉压和心率维持血流动力学稳定,麻醉和手术过程中未发生死亡事件。脑死亡小鼠供肝呈轻度的局部缺血性损伤(水肿、淤血、炎症浸润),假手术对照组小鼠供肝缺血性损伤程度较脑死亡组轻。结论本研究建模技术降低了手术难度和手术并发症,小鼠脑死亡模型稳定、可靠、具有可重复性。
