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一种合成磷酸钙纳米复合材料对大鼠肝癌发生的治疗作用

Therapeutic role of a synthesized calcium phosphate nanocomposite material on hepatocarcinogenesis in rats.

作者信息

Mohammed Magdy, Abdel-Gawad Eman, Awwad Sameh, Kandil Eman, El-Agamy Basma

机构信息

a Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt.

b Radioisotopes Department, Atomic Energy Authority, Cairo, Egypt.

出版信息

Biochem Cell Biol. 2016 Jun;94(3):279-88. doi: 10.1139/bcb-2015-0135.

Abstract

Nanotechnology research is booming worldwide, and the general belief is that medical and biological applications will form the greatest sector of expansion over the next decade. With this in mind, this study was designed to evaluate the therapeutic effects of a synthesized tricalcium phosphate nanocomposite material (nano-TCP) on hepatocarcinoma in a rat model, as initiated with diethylnitrosamine (DEN) and promoted with phenobarbital (PB). Hepatocarcinoma was induced with intraperitoneal injections of DEN (50 mg·(kg body mass)(-1)) 3 times a week for 2 weeks. Three weeks after the last dose of DEN, the rats received PB (0.05 %, w/v) in their drinking water for a further 6 weeks. Nano-TCP (100 mg·(kg body mass)(-1)) was administered intraperitoneally 3 times per week to rats with HCC. At the end of the experimental period, liver samples were collected from all animals for biochemical and histopathological analysis. The degree of DNA fragmentation was analyzed, in addition to immune status, by measuring the levels of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and interleukin-2 (IL-2). The activities of the most important free-radical scavengers of the antioxidant defense system as well as malondialdehyde (MDA) content and liver enzymes were measured. The levels of hepatic heat shock protein-70 (HSP-70), caspase-3, and metalloproteinase-9 were also measured as markers for inflammation and apoptosis. Histopathological examination of liver tissue was performed. The results revealed the potent efficacy of nano-TCP in repairing the fragmented DNA and ameliorating most of the investigated parameters by significant elevation in the levels of hepatic alanine aminotransferase (ALT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities. On the other hand, there was a significant decrease in hepatic gamma-glutamyl transpeptidase (γ-GT), MDA, IL-2, IFN-γ, TNF-α, matrix metalloproteinase-9 (MMP-9), HSP-70, and caspase-3 levels upon treatment. The findings form histopathological examination of the liver tissues agreed with the biochemical results and confirmed the difference between the control and treatment groups. In conclusion, nano-TCP succeeded in treating hepatocarcinoma efficiently, and presents a new hope for patients to get safe, fast, and effective treatment.

摘要

纳米技术研究在全球范围内蓬勃发展,人们普遍认为,医学和生物应用将在未来十年形成最大的扩张领域。考虑到这一点,本研究旨在评估一种合成的磷酸三钙纳米复合材料(纳米TCP)对大鼠肝癌模型的治疗效果,该模型由二乙基亚硝胺(DEN)引发,苯巴比妥(PB)促进。通过每周3次腹腔注射DEN(50 mg·(kg体重)(-1)),持续2周来诱导肝癌。在最后一剂DEN给药3周后,大鼠在饮用水中摄入PB(0.05%,w/v),持续6周。纳米TCP(100 mg·(kg体重)(-1))每周3次腹腔注射给肝癌大鼠。在实验期结束时,从所有动物收集肝脏样本进行生化和组织病理学分析。除了免疫状态外,还通过测量干扰素-γ(IFN-γ)、肿瘤坏死因子-α(TNF-α)和白细胞介素-2(IL-2)的水平来分析DNA片段化程度。测量了抗氧化防御系统中最重要的自由基清除剂的活性以及丙二醛(MDA)含量和肝酶。还测量了肝热休克蛋白-70(HSP-70)、半胱天冬酶-3和金属蛋白酶-9的水平,作为炎症和凋亡的标志物。对肝组织进行了组织病理学检查。结果显示,纳米TCP在修复片段化DNA以及通过显著提高肝丙氨酸转氨酶(ALT)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GPx)活性来改善大多数研究参数方面具有强大功效。另一方面,治疗后肝γ-谷氨酰转肽酶(γ-GT)、MDA、IL-2、IFN-γ、TNF-α、基质金属蛋白酶-9(MMP-9)、HSP-70和半胱天冬酶-3水平显著降低。肝脏组织的组织病理学检查结果与生化结果一致,并证实了对照组和治疗组之间的差异。总之,纳米TCP成功地有效治疗了肝癌,并为患者带来了获得安全、快速和有效治疗的新希望。

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