[關(guān)鍵詞]
[摘要]
目的 探討白藥子總生物堿對(duì) X 射線輻射損傷致小鼠白細(xì)胞減少的保護(hù)作用及其機(jī)制。方法 采用輻射法(一次性全身照射,照射劑量 2.5 Gy)制備白細(xì)胞減少癥小鼠模型,90 只昆明種小鼠隨機(jī)分為對(duì)照組,模型組,白藥子生物堿低、中、高劑量(1.25、2.50、5.00 mg·kg-1)組以及重組人粒細(xì)胞刺激因子(G-CSF)陽(yáng)性對(duì)照組,共 6 組,每組 15 只。除對(duì)照組外,各組小鼠均進(jìn)行 1 次性全身照射,白藥子總生物堿各組分別于照射前 3 d 及照射后連續(xù) ig 給藥 3、15 d,G-CSF 組于照射前 3 d sc 給藥,照射后 ig 給藥 15 d。實(shí)驗(yàn)結(jié)束后取小鼠股骨計(jì)算有核細(xì)胞數(shù)及 DNA 水平。處死小鼠后稱取小鼠肝臟、脾臟和胸腺質(zhì)量,計(jì)算臟器指數(shù)。采用血液學(xué)分析儀分別于照射前及照射后 3、7、15 d 對(duì)外周血細(xì)胞中的白細(xì)胞(WBC)進(jìn)行計(jì)數(shù)。收集小鼠血清,采用酶聯(lián)免疫吸附法檢測(cè)粒細(xì)胞-巨噬細(xì)胞集落刺激因子(GM-CSF)、血清 γ 干擾素(IFN-γ)、白細(xì)胞介素-3(IL-3)、白細(xì)胞介素-4(IL-4)、血管細(xì)胞黏附分子-1(VCAM-1)和可溶性細(xì)胞間黏附分子(SICAM-1)。通過(guò)蘇木精和伊紅染色檢測(cè)小鼠肝臟、脾臟的病理變化。電鏡觀察脾臟、肝臟的超微結(jié)構(gòu)。取肝臟組織,檢測(cè)抗氧化相關(guān)指標(biāo)。結(jié)果 白藥子總生物堿可以明顯抑制 X 射線照射后 14 d 內(nèi)外周血白細(xì)胞的減少,同時(shí)提高 X 射線輻射后的骨髓 DNA 水平及小鼠造血生長(zhǎng)因子 GM-CSF 水平,提高 X 射線輻射后免疫炎癥因子 IL-3、SICAM-1 水平,減輕肝臟和脾臟組織損傷,維持小鼠肝臟、脾臟正常功能,并顯著降低肝臟中的丙二醛(MDA)和黃嘌呤氧化酶(XOD)水平。結(jié)論 白藥子總生物堿增強(qiáng)免疫和造血功能,揭示其作為放射防護(hù)劑和輻射緩解劑的治療潛力。
[Key word]
[Abstract]
Objective To investigate the protective effect and the mechanism of the total alkaloids of Stephaniae Cepharantha Radix on leukopenia induced by X-ray radiation damage in mice. Methods A mouse model of leukopenia was made by radiation method (one-time whole-body irradiation, irradiation dose of 2.5 Gy). Kunming mice were randomly devided into six groups: control group, model group, total alkaloids of Stephaniae Cepharantha Radix low, medium, high dose (1.25, 2.50, 5.00 mg·kg-1) groups, and granulocyte colony-stimulating factor (G-CSF) positive control group with 15 animals in each group. Except for the control group, all groups of mice were subjected to one-time whole-body irradiation, and the total alkaloids of Stephaniae Cepharantha Radix were ig administered consecutively for 15 d before and after irradiation in each group, respectively, while the G-CSF group was sc administered for 3 d before irradiation and ig for 15 d after irradiation. The number of nucleated cells and DNA level were calculated after the experiment. Liver, spleen and thymus mass were weighed to calculate organ indices after execution of mice. White blood cells (WBC) in peripheral blood cells were counted before and 3, 7 15 d after, respectively, by using a hematology analyzer. Serum from mice were collected by enzyme-linked ELISA for granulocyte-macrophage colony-stimulating factor (GM-CSF), serum interferon (IFN-γ), interleukin-3 (IL-3), interleukin-4 (IL-4), vascular cell adhesion molecule 1 (VCAM-1) and soluble intercellular adhesion factor (SICAM-1). Pathologic changes in the liver and spleen of mice were detected by hematoxylin and eosin staining. The ultrastructure of spleen and liver was observed by electron microscopy. Liver tissue was obtained and tested for antioxidantrelated indices. Result It showed that the total alkaloids of Stephaniae Cepharantha Radix could significantly inhibit the reduction of peripheral blood leukocytes within 14 d after X-ray irradiation, at the same time increase the content of bone marrow DNA and the content of hematopoietic growth factor GM-CSF in mice after X-ray radiation, increase the content of immunoinflammatory factors IL-3 and SICAM-1 after X radiation, reduce the damage of liver and spleen tissues, maintain the normal function of the liver and spleen in mice, and significantly reduce the levels of malondialdehyde (MDA) and xanthine oxidase (XOD) in liver. Conclusion Enhancement of immune and hematopoietic functions by the total alkaloids of Stephaniae Cepharantha Radix reveals its therapeutic potential as a radioprotective and radiation mitigating agent.
[中圖分類號(hào)]
R285.5
[基金項(xiàng)目]