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miR-21-5p ameliorates Busulfan-induced testicular dysfunction and maintains spermatogenesis
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作者 Mengfei Zhang Shicheng Wan +15 位作者 Wenbo Chen Donghui Yang Congliang Wang Balun Li Aierken Aili Xiaomin Du Yunxiang Li Wenping Wu Yuqi Wang Fangde Xie Xuan Luo Na Li Xueling Li Lei Yang Ahmed Hamed Arisha Jinlian Hua 《Journal of Integrative Agriculture》 2025年第12期4744-4759,共16页
Spermatogonial stem cells(SSCs)are the key to maintaining production of the sperms and healthy offsprings,and also treating breeding livestock's reproductive damage and infertility.micro RNAs act a decisive role i... Spermatogonial stem cells(SSCs)are the key to maintaining production of the sperms and healthy offsprings,and also treating breeding livestock's reproductive damage and infertility.micro RNAs act a decisive role in regulating gene expression in many cells and tissues,including in processes such as proliferation,self-renewal,differentiation,and apoptosis of stem cells.However,the miRNA mechanism in regulation of SSCs is still unclear.Here,high-throughput sequencing was used to identify specific miRNAs.We confirmed that miR-21-5p was concentrated in both goat and mouse SSCs,and enhanced the proliferation and antiapoptotic ability of SSCs.In vivo experiments have shown that miR-21-5p resisted the damage of the chemotherapy drug Busulfan to germ cells,ameliorated Busulfan-induced testicular dysfunction,and maintained spermatogenesis.Further RNA-seq and target gene prediction revealed that SPRY1 and FASLG are targets of miR-21-5p,thereby activating downstream signaling pathways such as MAPK/ERK,PI3K-AKT,and apoptosis.In summary,miR-21-5p is crucial for the self-renewal and maintenance of SSCs.This study provides new avenues for treating breeding livestock's reproductive damages,infertility,oligospermia,and other conditions. 展开更多
关键词 miR-21-5p spermatogonial stem cells INFERTILITY busulfan apoptosis
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Optimal dose of busulfan for depleting testicular germ cells of recipient mice before spermatogonial transplantation 被引量:6
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作者 De-Zhi Wang Xin-Hua Zhou +1 位作者 Yu-Lin Yuan Xin-Min Zheng 《Asian Journal of Andrology》 SCIE CAS CSCD 2010年第2期263-270,共8页
Successful spermatogonial transplantation requires depletion of the host germ cells to allow efficient colonization of the donor spermatogonial stem cells. Although a sterilizing drug,busulfan (Myleran),is commonly ... Successful spermatogonial transplantation requires depletion of the host germ cells to allow efficient colonization of the donor spermatogonial stem cells. Although a sterilizing drug,busulfan (Myleran),is commonly used for preparing a recipient mouse before transplantation,the optimal dose of this drug has not yet been defined.The present study investigated the effects of different doses of busulfan (10-50 mg per kg body weight) on survival rate,testicular mass and histomorphology,and on the haploid spermatids and spermatozoa of male BALB/c mice.The results suggest that a dosage of 30 mg kg^-1 is optimal for the ablative treatment withbusulfan used to prepare the recipient mice. This dose results in an adequate depletion of the host germ cells for colonization of donorderived spermatogonial stem cells and causes the lowest death rate of the animals. 展开更多
关键词 busulfan germ cells infertility MICE myleran spermatogonial transplantation TESTIS
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Establishing a nonlethal and efficient mouse model of male gonadotoxicity by intraperitoneal busulfan injection 被引量:5
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作者 Yun Xie Cun-Can Deng +8 位作者 Bin Ouyang Lin-Yan Lv Jia-Hui Yao Chi Zhang Hai-Cheng Chen Xiao-Yan Liang Xiang-Zhou Sun Chun-Hua Deng Gui-Hua Liu 《Asian Journal of Andrology》 SCIE CAS CSCD 2020年第2期184-191,共8页
An ideal animal model of azoospermia would be a powerful tool for the evaluation of spermatogonial stem cell(SSC)transplantation.Busulfan has been commonly used to develop such a model,but 30%–87%of mice die when adm... An ideal animal model of azoospermia would be a powerful tool for the evaluation of spermatogonial stem cell(SSC)transplantation.Busulfan has been commonly used to develop such a model,but 30%–87%of mice die when administered an intraperitoneal injection of 40 mg kg^?1.In the present study,hematoxylin and eosin staining,Western blot,immunofluorescence,and quantitative real-time polymerase chain reaction were used to test the effects of busulfan exposure in a mouse model that received two intraperitoneal injections of busulfan at a 3-h interval at different doses(20,30,and 40 mg kg^?1)on day 36 or a dose of 40 mg kg^?1 at different time points(0,9,18,27,36,and 63 days).The survival rate of the mice was 100%.When the mice were treated with 40 mg kg^?1 busulfan,dramatic SSC depletion occurred 18 days later and all of the germ cells were cleared by day 36.In addition,the gene expressions of glial cell line-derived neurotrophic factor(GDNF),fibroblast growth factor 2(FGF2),chemokine(C-X-C Motif)ligand 12(CXCL12),and colony-stimulating factor 1(CSF1)were moderately increased by day 36.A 63-day,long-term observation showed the rare restoration of endogenous germ cells in the testes,suggesting that the potential period for SSC transplantation was between day 36 and day 63.Our results demonstrate that the administration of two intraperitoneal injections of busulfan(40 mg kg^?1 in total)at a 3-h interval to mice provided a nonlethal and efficient method for recipient preparation in SSC transplantation and could improve treatments for infertility and the understanding of chemotherapy-induced gonadotoxicity. 展开更多
关键词 AZOOSPERMIA busulfan gonadotoxicity INFERTILITY RECIPIENT preparation spermatogonial stem cell
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Accelerated ovarian aging in mice by treatment of busulfan and cyclophosphamide 被引量:3
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作者 Yan JIANG Jing ZHAO +5 位作者 Hui-jing QI Xiao-lin LI Shi-rong ZHANG Daniel W.SONG Chi-yang YU Jian-gang GAO 《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 SCIE CAS CSCD 2013年第4期318-324,共7页
Busulfan/cyclophosphamide(Bu/Cy) conditioning regimen has been widely used to treat cancer patients,while their effects on major internal organs in females are not fully understood.We treated female mice with Bu/Cy,an... Busulfan/cyclophosphamide(Bu/Cy) conditioning regimen has been widely used to treat cancer patients,while their effects on major internal organs in females are not fully understood.We treated female mice with Bu/Cy,and examined the histopathology of major internal organs on Day 30 after the treatment.The results show that Bu/Cy treatment affected the ovaries most extensively,while it had less effect on the spleen,lungs,and kidneys,and no effect on the heart,liver,stomach,and pancreas.To better understand the effect of Bu/Cy on the ovaries,we counted follicles,and determined the levels of ovarian steroids.The Bu/Cy-treated mice showed a reduction of primordial and primary follicles(P<0.01) on Day 30 and a marked loss of follicles at all developmental stages(P<0.01) on Day 60.Plasma levels of estradiol and progesterone in Bu/Cy-treated mice decreased by 43.9% and 61.4%,respectively.Thus,there was a gradual process of follicle loss and low estradiol in Bu/Cy-treated mice;this is a profile similar to what is found in women with premature ovarian failure(POF).The Bu/Cy-treated mice may serve as a useful animal model to study the dynamics of follicle loss in women undergoing POF. 展开更多
关键词 Premature ovarian failure busulfan CYCLOPHOSPHAMIDE CHEMOTHERAPY Mouse model
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Proliferation of exogenously injected primordial germ cells (PGCs) into busulfan-treated chicken embryos 被引量:2
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作者 H. Furuta N. Fujihara 《Asian Journal of Andrology》 SCIE CAS CSCD 1999年第4期187-190,共4页
Aim: This study was designed to investigate the effect of busulfan treatment on the proliferation of chicken primordialgerm cells (PGCs) in vivo, focusing on the preferential settlement of PGCs onto the germinal ridge... Aim: This study was designed to investigate the effect of busulfan treatment on the proliferation of chicken primordialgerm cells (PGCs) in vivo, focusing on the preferential settlement of PGCs onto the germinal ridges of chicken em-bryos. Methods: Busulfan (250 ng/egg) was injected into the egg white of freshly oviposited fertilized eggs, whichwere then incubated. Embryonic development and viability were examined, and exogenous PGCs collected from embry-onic blood vessels were injected into the germinal crescent region of recipient embryos. The number of PGCs residedonto germinal ridges of the right and left sides were compared. Results: Busulfan had a slight harmful effect on theembryo viability and the PGCs proliferation. The number of PGCs resided onto the left side of germinal ridges wasslightly higher as compared with the right side. Conclusion: Busulfan suppressed the viability of embryos and the pro-liferation of endogenous PGCs in the recipient embryos. However, the number of exogenous PGCs proliferated washigher in embryos treated with busulfan than those without busulfan. Data also suggest the possibility of a preferentialresidence of PGCs toward the left side of the germinal crescent region as compared with the fight, which may be due toa more advanced functional development of the left gonad than the right. (Asian J Androl 1999 Dec; 1: 187-190) 展开更多
关键词 chick embryo germ cells PROLIFERATION busulfan
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Screening for urinary markers predicting hematopoietic stem cell injury induced by busulfan using genetically diverse mice 被引量:1
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作者 Yuhang Sun Bowen Guan +4 位作者 Xing Liu Lingyan Zhang Xinpei Wang Aimin Meng Ran Gao 《Animal Models and Experimental Medicine》 CAS CSCD 2023年第2期146-154,共9页
Background:Busulfan(BU)is an alkylating agent used as a conditioning agent prior to hematopoietic stem cell(HSC)transplantation as it is known to be cytotoxic to host hematopoietic stem and progenitor cells.The suscep... Background:Busulfan(BU)is an alkylating agent used as a conditioning agent prior to hematopoietic stem cell(HSC)transplantation as it is known to be cytotoxic to host hematopoietic stem and progenitor cells.The susceptibility of HSCs to BU injury plays an important role in the myeloablative efficacy of BU.Different susceptibilities were demonstrated in genetically diverse(GD)mice in our preliminary research.Methods:Three strains of GD mice with different susceptibilities to BU-i nduced HSC injury were used for screening biological markers of HSC injury susceptibility in urine.The urine proteins were analyzed using liquid chromatography coupled with tandem mass spectrometry to screen for differentially expressed proteins.Screening for possible biomarkers based on differences in protein expression abundance was validated using enzyme-l inked immunoassay(ELISA).Results:Functional analysis showed that the differential proteins were all involved in a series of biological pathways related to cellular senescence,apoptosis,and angiogenesis;whereas the differential proteins of the high-susceptible strain were enriched for the regulation of bone marrow microenvironment pathways,those of low-susceptible strain were enriched for the proapoptotic effect of GTPase pathways.Based on protein abundance differences,several urinary proteins that may be indicative of susceptibility were screened,and ELISA validation results showed that angiotensin-converting enzyme may be a potential biomarker predicting HSC susceptibility for BU conditioning.Conclusions:This study indicates that urinary protein levels can reflect differences in susceptibility to BU-i nduced HSC injury.Using GD mice to construct genetic difference models will provide preclinical data for screening BU-related biological markers. 展开更多
关键词 angiotensin I converting enzyme busulfan hematopoietic stem cell injury inbred genetic diversity mice urinary marker
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Ameliorative effects of melatonin and zinc oxide nanoparticles treatment against adverse effects of busulfan induced infertility in male albino mice
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作者 AMOURA M.ABOU-EL-NAGA SHAKER A.MOUSA +2 位作者 FAYEZ ALTHOBAITI EMAN FAYAD ENGY S.FAHIM 《BIOCELL》 SCIE 2022年第2期535-545,共11页
Testicular damage is one of the most hazardous effects as it’s associated with azoospermia.Busulfan(Bu)is a highly toxic chemotherapeutic drug that affects testis.Thirty male Swiss albino mice divided into six groups... Testicular damage is one of the most hazardous effects as it’s associated with azoospermia.Busulfan(Bu)is a highly toxic chemotherapeutic drug that affects testis.Thirty male Swiss albino mice divided into six groups of 5 animals each.Control(oral 0.9%saline daily for 75 days);Mel(20 mg/kg/day orally for 30 days);ZnO NPs(5 mg/kg/day i.p.for 30 days);BU(single i.p.injection of 40 mg/kg and then left for 45 days);BU+Mel(single 40 mg/kg dose of BU and left for 45 days followed by 20 mg/kg/day Mel for 30 days);BU+ZnO NPs(single dose of 40 mg/kg of BU and left for 45 days,then 5 mg/kg/day ZnO NPs for 30 days).Preparation and Characterization of ZnO NPs.Specimens from testis prepared for ultrastructural investigations using TEM after Masson’s trichrome and toluidine blue staining.BU induced histological and ultrastructural damage of the testis.Moreover,the present results could be concluded that Mel or ZnO NPs can protect the testicular tissue against ultrastructural alterations induced by BU by its antioxidant and anti-apoptotic effects. 展开更多
关键词 busulfan MELATONIN Zinc oxide nanoparticles ULTRASTRUCTURE TESTIS Mice
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Protective effects of honey compound syrup on busulfan-induced azoospermia in male rats
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作者 Seyyed Shamsadin Athari Keivan Lorian +2 位作者 Haniye Kashafroodi Saadat Ghafarzadeh Rasool Choopani 《Asian pacific Journal of Reproduction》 2021年第6期284-290,共7页
Objective:To evaluate the protective effects of honey compound syrup on sperm count and testis tissue in rats.Methods:Thirty rats were randomly assigned to five groups.The control group received 1 mL normal saline wit... Objective:To evaluate the protective effects of honey compound syrup on sperm count and testis tissue in rats.Methods:Thirty rats were randomly assigned to five groups.The control group received 1 mL normal saline with dimethyl sulfoxide intraperitoneally;the busulfan group received busulfan 10 mg/kg body weight at the first and twenty-first days of the experiment via intraperitoneal injection;the last three groups received busulfan 10 mg/kg body weight to induce azoospermia,and then received 1.0,1.5,or 2.0 mg/kg honey compound syrup,respectively,after induction of azoospermia.After administration,the testis and epididymis of all rats were removed.Then,reproductive organ weight and sperm parameters(sperm concentration,epididymal sperm reserve and daily sperm production)were measured.After hematoxylin-eosin staining,seminiferous tubule cells and diameters were assessed.Results:Busulfan damaged the testis tissue and impaired spermatogenesis.Administration of honey compound syrup in three doses improved testis tissue and spermatogenesis.The protective effects of honey compound syrup may relate to the antioxidant properties of honey and other compounds in this syrup.Conclusions:Administration of honey compound syrup could be an ameliorative agent for the side effects of chemotherapy drugs such as busulfan on the male reproductive system. 展开更多
关键词 busulfan AZOOSPERMIA Honey compound syrup Sperm Rat Iranian traditional medicine
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Allogeneic and autologous stem cell transplantation with busulfan, cyclophosphamide, and etoposide conditioning therapy for relapsed/refractory non-Hodgkin lymphoma
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作者 Neelima Vidula Andrew M. Evens +9 位作者 Irene B. Helenowski Borko Jovanovic Jane N. Winter Jayesh Mehta Seema Singhal Stephanie F. Williams Olga Frankfurt Jessica K. Altman Joanne Monreal Leo I. Gordon 《Modern Chemotherapy》 2013年第4期57-65,共9页
The optimal stem cell transplantation (SCT) conditioning therapy for relapsed/refractory non-Hodgkin lymphoma (NHL) is not clearly defined. In a retrospective analysis, we examined 25 patients with “high risk” relap... The optimal stem cell transplantation (SCT) conditioning therapy for relapsed/refractory non-Hodgkin lymphoma (NHL) is not clearly defined. In a retrospective analysis, we examined 25 patients with “high risk” relapsed/refractory NHL who received busulfan, cyclophosphamide, and etoposide (Bu/Cy/VP16) conditioning with autologous or allogeneic SCT. The majority of patients had aggressive histology and 52% had primary refractory NHL. Furthermore, 48% of patients had chemotherapy-resistant disease at the time of SCT. Fifty-six percent of patients underwent allogeneic SCT, while 44% had autologous SCT. The median engraftment time for neutrophils and platelets was 13.5 and 14 days, respectively. The 100-day treatment-related mortality (TRM) was 16%, while the 2-year non-relapse mortality (NRM) rate was also 16%. At a median follow-up of 15 months, the estimated 2-year disease-free survival (DFS) rate was 64% (95% confidence interval (CI): 36%-82%) and the estimated 2-year overall survival (OS) was 69% (95% CI: 40%-86%). Furthermore, the 2-year disease-specific survival (DSS) rate was 73% (95% CI: 40%-90%). Using Cox proportional hazard modeling, the International Prognostic Index at time of relapse predicted DFS and OS. Altogether, Bu/Cy/VP16 was associated with early TRM;however, late toxicities (including NRM) were uncommon resulting in relatively good survival rates in a high-risk relapsed/refractory NHL population. 展开更多
关键词 Stem Cell Transplantation busulfan CYCLOPHOSPHAMIDE ETOPOSIDE NON-HODGKIN Lymphoma
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苯妥英钠与左乙拉西坦对造血干细胞移植患儿白消安血药浓度的影响
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作者 徐世希 曾广庭 +6 位作者 王静宇 刘淑兰 刘静 邓铂彦 罗继名 林杰 王安发 《中国当代儿科杂志》 北大核心 2025年第11期1378-1383,共6页
目的研究预防性使用苯妥英钠(phenytoin,PHT)或左乙拉西坦(levetiracetam,LEV)对造血干细胞移植患儿白消安(busulfan,BU)血药浓度的影响。方法回顾性纳入郴州市第一人民医院2023年9月—2025年2月接受BU+环磷酰胺+氟达拉滨预处理的造血... 目的研究预防性使用苯妥英钠(phenytoin,PHT)或左乙拉西坦(levetiracetam,LEV)对造血干细胞移植患儿白消安(busulfan,BU)血药浓度的影响。方法回顾性纳入郴州市第一人民医院2023年9月—2025年2月接受BU+环磷酰胺+氟达拉滨预处理的造血干细胞移植患儿,按预防性抗癫痫方案分为PHT组(24例)与LEV组(26例),比较两组BU血药浓度的差异。结果BU滴注完0 h时,两组BU血药浓度比较差异无统计学意义(P>0.05)。BU滴注完1 h、2 h、4 h时,LEV组BU血药浓度均高于PHT组(P<0.05)。LEV组BU药时曲线下面积_(0~∞)(area under the drug concentration time curve from 0 to∞,AUC_(0~∞))大于PHT组(P<0.001),且LEV组AUC_(0~∞)达标率高于PHT组(73%vs 21%,P<0.001)。两组间造血细胞植活时间及BU的药物不良反应发生率比较差异无统计学意义(P>0.05)。结论相较PHT,使用LEV预防癫痫时,BU的血药浓度和AUC_(0~∞)达标率更高。暂未发现PHT及LEV对BU的疗效及安全性影响有差异。 展开更多
关键词 白消安 苯妥英钠 左乙拉西坦 血药浓度监测 药物相互作用 造血干细胞移植 儿童
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白消安缓释剂对鸡内源性生殖细胞消减能力和孵化性能的影响
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作者 杜洪峰 葛采月 +7 位作者 张洲颖 章琦 倪爱心 韩昕彤 李云雷 陈继兰 刘胜军 孙研研 《中国农业大学学报》 北大核心 2025年第11期136-144,共9页
为分析种蛋中注射白消安对鸡内源性生殖细胞的消减能力和孵化性能的影响,以寻求最优化的使用方式,本研究采用芝麻油和乳化器制备白消安缓释剂,分别按照最终注射白消安剂量为每个蛋0(不注射的空白对照组和只注射不含白消安的试剂的试验... 为分析种蛋中注射白消安对鸡内源性生殖细胞的消减能力和孵化性能的影响,以寻求最优化的使用方式,本研究采用芝麻油和乳化器制备白消安缓释剂,分别按照最终注射白消安剂量为每个蛋0(不注射的空白对照组和只注射不含白消安的试剂的试验对照组)、50、75和100μg注射到孵化3 h的种蛋的卵黄中,比较各组鸡胚内源性生殖细胞消减情况和孵化性能。结果表明:1)白消安注射引起7胚龄性腺中原始生殖细胞数量显著减少(P<0.05),具备很好的消减能力,其中75和100μg组原始生殖细胞数量差异不显著(P>0.05),但显著少于对照组和50μg组(P<0.05)。2)在孵化性能方面,75μg组死胚率(43.2%)远小于100μg组(71.6%)。3)雏鸡及死胚解剖发现各试验组性腺相对较小,部分消化道(肌胃)受到不同程度损伤。综上,白消安缓释剂可以有效去除内源性生殖细胞,并成功孵化,75μg/蛋的剂量是制备移植受体的最适浓度,而在控制死胚率方面仍然有很大研究空间。 展开更多
关键词 白消安 不育受体 种系传播率 毒性作用
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褪黑素通过抑制铁死亡改善环磷酰胺和白消安诱导的早发性卵巢功能不全小鼠的研究
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作者 裴娇娇 腊晓琳 《中国医药科学》 2025年第8期4-8,21,共6页
目的探讨褪黑素通过抑制铁死亡途径对环磷酰胺和白消安诱导的早发性卵巢功能不全(POI)小鼠的保护作用及机制。方法选用6周龄CD1雌性小鼠,随机分为对照组、POI组和POI+褪黑素组。建立POI模型后,检测小鼠体重、卵巢湿重、血清激素水平、... 目的探讨褪黑素通过抑制铁死亡途径对环磷酰胺和白消安诱导的早发性卵巢功能不全(POI)小鼠的保护作用及机制。方法选用6周龄CD1雌性小鼠,随机分为对照组、POI组和POI+褪黑素组。建立POI模型后,检测小鼠体重、卵巢湿重、血清激素水平、卵泡计数及铁死亡相关指标。结果POI组小鼠体重、卵泡数量及激素水平显著低于对照组(P<0.05),铁死亡标志物丙二醛、核因子E2相关因子2、溶质载体家族7成员11、谷胱甘肽过氧化物酶4均升高(P<0.01)。褪黑素干预后,小鼠体重、卵泡数量、血清激素水平均显著改善(P<0.05),铁死亡相关标志物丙二醛、谷胱甘肽及核因子E2相关因子2表达水平显著降低(P<0.01)。结论褪黑素通过抑制铁死亡途径改善POI,具有潜在临床应用价值。 展开更多
关键词 早发性卵巢功能不全 铁死亡 褪黑素 环磷酰胺 白消安
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HPLC-MS/MS同时快速测定儿童微量血浆中白消安与苯妥英
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作者 丁维靖 姜锡娟 +1 位作者 秦亚彬 赵宜乐 《中国医院药学杂志》 北大核心 2025年第10期1106-1111,共6页
目的:建立一种高效液相色谱串联质谱法(HPLC-MS/MS)同时测定儿童微量血浆中白消安与苯妥英,用于接受造血干细胞移植患儿的治疗药物监测。方法:采用甲醇沉淀蛋白法处理儿童血浆样品,以Phenomenex Kinetex EVO C_(18)(30 mm×2.1 mm,... 目的:建立一种高效液相色谱串联质谱法(HPLC-MS/MS)同时测定儿童微量血浆中白消安与苯妥英,用于接受造血干细胞移植患儿的治疗药物监测。方法:采用甲醇沉淀蛋白法处理儿童血浆样品,以Phenomenex Kinetex EVO C_(18)(30 mm×2.1 mm,2.6μm)色谱柱分离2种化合物,流动相为2 mmol·L^(–1)乙酸铵+0.1%甲酸水(A)和2 mmol·L^(–1)乙酸铵+0.1%甲酸乙腈(B)梯度洗脱;质谱检测采用电喷雾离子源正离子模式,并通过多反应监测扫描方式进行分析,监测离子对:白消安m/z 264.0→151.1,苯妥英m/z 253.1→182.1,采用稳定同位素内标法定量。结果:白消安在质量浓度20~2560ng·mL^(–1)范围内线性关系良好(r=0.9994),苯妥英在0.4~51.2μg·mL^(–1)范围内线性关系良好(r=0.9958),其准确度、精密度、稳定性和基质效应等均符合要求。将建立并经过验证的检测方法成功应用于3例接受造血干细胞移植治疗前同时使用白消安和苯妥英的患儿血药浓度测定。结论:该法操作简便快速,仅需微量血浆即可准确定量,可用于接受造血干细胞移植前患儿血浆中白消安和苯妥英的治疗药物监测。 展开更多
关键词 HPLC-MS/MS 白消安 苯妥英 治疗药物监测
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白消安消除鸡内源性原始生殖细胞的作用机制与应用研究
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作者 彭溢秀 《现代牧业》 2025年第1期13-18,共6页
白消安(Busulfan)作为一种传统的烷化抗癌药,广泛应用于临床治疗,但其生殖毒性显著。近年来,白消安在鸡胚中消除内源性原始生殖细胞(PGCs)的研究受到关注。PGCs作为生殖细胞前体细胞,在生殖系统发育和遗传信息传递中发挥着关键作用。而... 白消安(Busulfan)作为一种传统的烷化抗癌药,广泛应用于临床治疗,但其生殖毒性显著。近年来,白消安在鸡胚中消除内源性原始生殖细胞(PGCs)的研究受到关注。PGCs作为生殖细胞前体细胞,在生殖系统发育和遗传信息传递中发挥着关键作用。而消除内源性PGCs为研究生殖系统的重建和基因编辑技术以及转基因模型的构建提供了理想的实验平台。综述了白消安在鸡PGCs消除中的作用机制、应用方法及在转基因技术、遗传改良与物种保护中的潜在应用。通过分析现有研究成果与面临的挑战,为未来白消安在生殖生物学和农业领域的进一步应用提供了参考,并探讨了该技术的伦理问题和发展方向。 展开更多
关键词 白消安 消除 原始生殖细胞
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淫羊藿苷改善白消安联合环磷酰胺诱导的雄性小鼠生殖功能损伤的作用研究
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作者 吴瑶 时姗姗 +3 位作者 柳海燕 黄皓 石兴华 侯景 《中华男科学杂志》 2025年第1期25-33,共9页
目的:通过小鼠体内外实验综合评价淫羊藿苷对雄性小鼠生殖功能损伤的缓解作用。方法:体外分离KM小鼠睾丸间质细胞,CCK-8法考察淫羊藿苷对小鼠睾丸间质细胞的毒性影响;KM小鼠随机分成6组,分别为正常对照组,模型对照组(白消安10 mg/kg联... 目的:通过小鼠体内外实验综合评价淫羊藿苷对雄性小鼠生殖功能损伤的缓解作用。方法:体外分离KM小鼠睾丸间质细胞,CCK-8法考察淫羊藿苷对小鼠睾丸间质细胞的毒性影响;KM小鼠随机分成6组,分别为正常对照组,模型对照组(白消安10 mg/kg联合环磷酰胺120 mg/kg给药3 d),建模后淫羊藿苷低、中、高剂量给药组(淫羊藿苷灌胃20、40、80 mg/kg)以及阳性对照组(五子衍宗丸灌胃2 g/kg),连续给药30 d,生殖脏器称重计算脏器系数,并进行精子计数;HE染色观察睾丸组织病理学变化;ELISA法检测血清睾酮水平;比色法检测睾丸氧化应激指标和NO信号通路指标;qPCR法检测促凋亡基因Fas、Bax的表达情况。结果:细胞实验证实淫羊藿苷对分离的小鼠睾丸间质细胞无毒性作用,并可有效减少环磷酰胺、白消安诱导的细胞毒性作用,促进睾酮的分泌。小鼠生殖功能损伤模型结果显示,80 mg/kg的淫羊藿苷能显著提高睾丸脏器指数、促进精子生成量(P<0.05),但对附睾脏器指数影响较小。睾丸组织形态学观察发现淫羊藿苷处理后小鼠睾丸结构显著改善,生精小管界膜完整,各类生精细胞数量增多。小鼠睾丸氧化应激结果分析可知,与模型对照组比较,淫羊藿高剂量组中MDA含量显著降低(P<0.01),T-AOC、T-SOD表达量显著上升(P<0.05);同时,睾丸组织中NO含量和NOS酶活水平较模型对照组显著下降(P<0.01)。qPCR结果显示淫羊藿苷对促凋亡基因Bax和Fas的mRNA水平表达呈现出抑制作用。结论:淫羊藿苷可能通过提升睾丸抗氧化水平,降低NOS活性进而抑制NO水平,并调节白消安和环磷酰胺诱导的睾丸细胞凋亡作用,从而改善氧化应激状态对小鼠睾丸功能的损伤,发挥睾丸生精功能的保护作用。 展开更多
关键词 淫羊藿苷 环磷酰胺 白消安 生殖功能 氧化应激 小鼠
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不同剂量白消安对ICR雄性小鼠生精功能障碍影响
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作者 栾晓花 吕跃 张再新 《系统医学》 2025年第8期1-5,共5页
目的探讨不同剂量的白消安对ICR雄性小鼠生精功能的影响。方法2023年1—12月于山东大学妇儿与生殖健康研究院(山东大学附属生殖医院)开展本研究,共纳入60只ICR雄性小鼠,按随机数字表法分为对照组和造模组。其中,对照组小鼠腹腔注射等量... 目的探讨不同剂量的白消安对ICR雄性小鼠生精功能的影响。方法2023年1—12月于山东大学妇儿与生殖健康研究院(山东大学附属生殖医院)开展本研究,共纳入60只ICR雄性小鼠,按随机数字表法分为对照组和造模组。其中,对照组小鼠腹腔注射等量二甲基亚砜;造模组根据白消安剂量不同进一步分为模型1组(20 mg/kg)、模型2组(30 mg/kg)和模型3组(40 mg/kg),每组15只。实验过程中,分别于造模第2周、3周、4周检测各组小鼠的精子浓度、精子活力、体质量、睾丸湿重及组织病理学变化,以评估白消安对小鼠生精功能的影响。结果造模第2周和第3周,各组小鼠精子活力比较,差异均无统计学意义(P均>0.05);第4周,模型2组精子活力为(63.41±6.85)%、模型3组精子活力为(59.15±6.83)%,均低于对照组的(78.17±7.95)%,差异均有统计学意义(t=5.447,7.028;P均<0.05)。造模第3周,模型1组、模型2组、模型3组的精子浓度低于对照组;第4周,模型1组、模型2组、模型3组的精子浓度均低于对照组,差异均有统计学意义(P均<0.05)。各组小鼠体质量变化比较,差异均无统计学意义(P均>0.05)。造模第3周,模型1组、模型2组、模型3组的睾丸湿重低于对照组;第4周,模型1组、模型2组、模型3组的睾丸湿重均低于对照组,差异均有统计学意义(P均<0.05)。结论随着造模时间的增加,白消安剂量达到20 mg/kg时,就会对生精功能造成影响,随着剂量、时间的增加,影响越严重。 展开更多
关键词 白消安 小鼠实验 生精功能 不育
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High dose melphalan (HDM) is superior to cyclophosphamide plus etoposide and busulfan (CVB) as the conditioning regimen in autologous stem cell transplantation for multiple myeloma
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作者 GU Jingli 《China Medical Abstracts(Internal Medicine)》 2019年第4期230-231,共2页
Objective To compare the efficacy,response and survival between high-dose melphalan(HDM)and cyclophosphamide+etoposide+busulfan(CVB)as the conditioning regimen in autologous stem cell transplantation(ASCT)for newly di... Objective To compare the efficacy,response and survival between high-dose melphalan(HDM)and cyclophosphamide+etoposide+busulfan(CVB)as the conditioning regimen in autologous stem cell transplantation(ASCT)for newly diagnosed multiple myeloma(NDMM).Methods 123 consecutive NDMM patients who had received PAD induction with subsequent ASCT from Jan 2011 to Aug 2017 were retrospectively studied.The CVB group and HDM group had 82 and 41 patients respectively.Results①No differences existed between these 2 groups in non-hematological side effects. 展开更多
关键词 HDM CVB busulfan
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基于FAERS数据库的白消安不良事件信号挖掘与分析 被引量:5
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作者 王广飞 张俊琦 +3 位作者 黄怡蝶 王月玥 翟晓文 李智平 《药物流行病学杂志》 CAS 2024年第3期259-268,共10页
目的 利用美国食品药品管理局不良事件报告系统(FAERS)数据库对白消安的药品不良事件(ADE)进行研究,挖掘潜在的ADE信号,为临床安全用药提供参考。方法 检索FAERS数据库中2004年第1季度至2023年第1季度的数据,通过数据清洗、目标药物名... 目的 利用美国食品药品管理局不良事件报告系统(FAERS)数据库对白消安的药品不良事件(ADE)进行研究,挖掘潜在的ADE信号,为临床安全用药提供参考。方法 检索FAERS数据库中2004年第1季度至2023年第1季度的数据,通过数据清洗、目标药物名称标准化,获得以白消安为首要怀疑药物的ADE记录。采用报告比值比法、比例报告比值法和综合标准法挖掘白消安ADE信号,并利用信息成分法进行信号强弱判断。以《国际医学用语词典》对ADE进行系统器官分类(SOC),并按照ADE发生频次和信号强度分别排序。结果 共获得20 326份以白消安为首要怀疑药物的ADE报告,涉及患者5 615例,男性患者比例高于女性(40.71%vs.30.74%);年龄小于18岁占31.56%;上报人群主要为医师(33.71%)、其他健康专业人员(24.35%)以及药师(23.86%);上报国家主要为美国(29.69%)、日本(15.78%)、法国(11.79%)。共挖掘出白消安相关ADE信号556个,其中117个ADE信号未被药品说明书收载。556个ADE信号中,发生频次前五位ADE分别为产品用于未经批准的适应证、肝小静脉闭塞症、黏膜炎症、巨细胞病毒感染和移植物抗宿主病;信号强度排名前五位ADE分别为肝小静脉闭塞症、急性移植物抗宿主病、静脉闭塞性疾病、移植物抗宿主病以及慢性移植物抗宿主病。挖掘的ADE信号共累及23个SOC,数量排名前三的SOC分别为感染及侵染类疾病,各类检查,良性、恶性及性质不明的肿瘤(包括囊状和息肉状)。结论 白消安临床应用中,应警惕肝小静脉闭塞症、感染、移植物抗宿主病、神经相关毒性和血栓性微血管病等易造成严重后果的ADE,临床药师协助医师做好ADE的预防方案,提高白消安的使用安全性。 展开更多
关键词 白消安 FAERS数据库 药品不良事件 信号挖掘 药物警戒
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脊髓损伤模型小胶质细胞的高效移植替换策略
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作者 曾凡卓 李雨欣 +4 位作者 孙嘉晨 谷欣阳 文山 田鹤 梅晰凡 《中国组织工程研究》 CAS 北大核心 2024年第7期1007-1014,共8页
背景:由于脊髓损伤的发生率逐年升高,且脊髓损伤后神经再生困难,因此如何促进脊髓损伤的恢复和提高脊髓损伤后干细胞及其他治疗细胞的移植效率,一直是临床及科研的研究热点和重点。目的:建立脊髓损伤模型小鼠脊髓小胶质细胞高效率移植... 背景:由于脊髓损伤的发生率逐年升高,且脊髓损伤后神经再生困难,因此如何促进脊髓损伤的恢复和提高脊髓损伤后干细胞及其他治疗细胞的移植效率,一直是临床及科研的研究热点和重点。目的:建立脊髓损伤模型小鼠脊髓小胶质细胞高效率移植替换的方式。方法:选取8-10周龄CX3CR1 creER^(-/+)::LSL-BDNF^(-/+)-tdTomato小鼠,CX3CR1^(+/GFP)小鼠,β-actin GFP小鼠及C57BL/6J野生型小鼠。按照实验要求随机分为6组:(1)假手术组:只掀除小鼠椎板而不做损伤,使用8只基因型为C57BL/6J野生型小鼠;(2)脊髓打击损伤组:使用8只基因型为C57BL/6J野生型小鼠;(3)脊髓钳夹损伤组,使用8只基因型为C57BL/6J野生型小鼠;(4)连体共生脊髓打击损伤组:通过手术将血液发绿色荧光的β-actin GFP小鼠与C57BL/6J野生型小鼠分别缝合在一起,使用8只β-actin GFP小鼠和8只C57BL/6J野生型小鼠;(5)Mr BMT-X Ray组(PLX5622清除脊髓小胶质细胞加X射线辐射清髓移植组):将4只CX3CR1 cre ER^(-/+)::LSL-BDNF^(-/+)-tdTomato小鼠骨髓细胞移植给8只C57BL/6J野生型小鼠并进行脊髓打击损伤造模;(6)Mr BMT-Busulfan组(PLX5622清除脊髓小胶质细胞加Busulfan清髓移植组):将4只CX3CR1^(+/GFP)小鼠的骨髓细胞移植给8只C57BL/6J野生型小鼠,只观察细胞移植替换比例,不进行脊髓损伤造模处理。假手术组、脊髓打击损伤组、脊髓钳夹损伤组小鼠在脊髓损伤后第14天灌流取材,连体共生脊髓打击损伤组小鼠在脊髓损伤后第7天灌流取材,Mr BMT-X Ray组小鼠在脊髓损伤后第28天灌流取材,Mr BMT-Busulfan组在移植后第28天灌流取材,取材部位为以小鼠脊髓T10节段为中心共1.2 cm长的脊髓;为观察Mr BMT-X Ray组和Mr BMT-Busulfan组是否会发生脑部的移植替换,故需额外留存小鼠的脑组织。通过使用转基因小鼠、连体共生及免疫荧光检测损伤区域移植和替换的细胞数目与比例。结果与结论:与传统的经外周血移植方式即连体共生脊髓打击损伤组小鼠的细胞移植效率(9.8%)相比,新型移植方式Mr BMT-X Ray和Mr BMT-Busulfan可以大幅度提高脊髓小胶质细胞的移植替换比例,分别可以达到84.8%和95.6%,差异有显著性意义(P<0.05)。结果表明,新型的细胞移植方式Mr BMT-X Ray和Mr BMT-Busulfan可以实现脊髓小胶质细胞的高效率替换,可以改善传统细胞移植方式存在的细胞移植效率低、存活数目少及分化不清楚的问题,并且Mr BMT-X Ray可以实现仅替换小鼠的脊髓小胶质细胞,而Mr BMT-Busulfan则可以避免X射线辐射移植方式可能造成的脑部炎症和损伤。 展开更多
关键词 脊髓损伤 细胞移植替换 小胶质细胞 巨噬细胞 Mr BMT-X Ray Mr BMT-busulfan
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褪黑素缓解白消安损伤小鼠睾丸的机理研究
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作者 吴开慧 张留光 +5 位作者 汪超 许师源 刘松奇 原开敏 王栋 庞云渭 《畜牧兽医学报》 CAS CSCD 北大核心 2024年第6期2486-2497,共12页
旨在揭示褪黑素(melatonin, MT)缓解白消安损伤睾丸的机理,提高白消安制备精原干细胞移植受体的效率,并探究其对白消安毒害雄性生精机能的治疗作用。本研究以6~7周ICR雄鼠为模型动物,分为对照组,白消安处理组和白消安+褪黑素处理组,每组... 旨在揭示褪黑素(melatonin, MT)缓解白消安损伤睾丸的机理,提高白消安制备精原干细胞移植受体的效率,并探究其对白消安毒害雄性生精机能的治疗作用。本研究以6~7周ICR雄鼠为模型动物,分为对照组,白消安处理组和白消安+褪黑素处理组,每组8个重复,于注射后第7天取样。通过ELISA检测睾丸组织的炎性细胞因子水平,并对睾丸和附睾进行HE染色。此外,免疫组化或免疫荧光检测血睾屏障(blood-testis barrier, BTB)相关蛋白的表达情况,以分析MT对BTB影响。结果表明,小鼠经白消安注射后,联合MT处理,观察到MT显著缓解了睾丸重和睾体率下降的趋势,并减缓了精子数量下降的速度;睾丸组织HE染色和炎性细胞因子检测发现,MT显著减缓了核转录因子κB(nuclear transportation factorκB,NF-κB)、p-NF-κB、白介素-1β(interleukin-1β,IL-1β)、肿瘤坏死因子-ɑ(tumor necrosis factor-ɑ,TNF-α)及髓过氧化物酶(myeloperoxidase, MPO)水平的上升趋势,从而减少了组织中炎性细胞浸润;免疫组化或免疫荧光检测发现,MT缓解了白消安处理导致的BTB组成蛋白(Occludin、connexin-43、N-cadherin)和细胞骨架蛋白(F-actin和Vimentin)含量的下降。综上,MT通过下调睾丸组织中炎性细胞因子水平,缓解白消安诱发的小鼠睾丸炎症反应;并通过减缓BTB相关蛋白含量的下降,缓解白消安对BTB和支持细胞的损伤,进而缓解小鼠生精机能的损伤。 展开更多
关键词 褪黑素 白消安 睾丸炎 血睾屏障 细胞骨架
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