[1]李晓博,郭亚鹏,姜 海,等.阿糖胞苷诱导母鼠成纤维细胞生长因子4表达情况及其与胎鼠多指畸形关系研究[J].陕西医学杂志,2022,51(6):659-663.[doi:DOI:10.3969/j.issn.1000-7377.2022.06.004]
　LI Xiaobo,GUO Yapeng,JIANG Hai,et al.Expression of fibroblast growth factor 4 in maternal rats induced by cytarabine and its relationship with polydactyly in fetal rat[J].,2022,51(6):659-663.[doi:DOI:10.3969/j.issn.1000-7377.2022.06.004]
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阿糖胞苷诱导母鼠成纤维细胞生长因子4表达情况及其与胎鼠多指畸形关系研究
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《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
51
期数:
2022年6期
页码:
659-663
栏目:
基础研究
出版日期:
2022-06-05

文章信息/Info

Title:
Expression of fibroblast growth factor 4 in maternal rats induced by cytarabine and its relationship with polydactyly in fetal rat
作者:
李晓博1; 郭亚鹏1; 姜 海1; 同毓龙1; 李 涛1; 陈 明2
(1.西北妇女儿童医院骨科,陕西 西安 710061; 2.空军军医大学唐都医院骨科,陕西 西安 710038)
Author(s):
LI Xiaobo; GUO Yapeng; JIANG Hai; TONG Yulong; LI Tao; CHEN Ming
(Department of Orthopedics,Northwest Women's and Children's Hospital,Xi'an 710061,China)
关键词:
阿糖胞苷;  成纤维细胞生长因子4;  多指畸形;  氧化应激;  炎症因子;  关系
Keywords:
Cytarabine;  Fibroblast growth factor 4;  Polydactyly;  Oxidative stress;  Inflammatory factor;  Relationship
分类号:
R 682.1
DOI:
DOI:10.3969/j.issn.1000-7377.2022.06.004
文献标志码:
A
摘要:
目的:探究阿糖胞苷诱导母鼠成纤维细胞生长因子4(FGF4)的表达情况,分析其与胎鼠多指畸形的关系。方法:16只雌性大鼠和8只雄性大鼠以2:1比例交配。受孕后第8天将大鼠分为对照组(健康受孕大鼠,8只)和糖胞苷诱导组(妊娠第11天早晨以100 mg/kg的剂量腹腔注射阿糖胞苷,8只)。比较两组大鼠受孕后不同时间点体重。比较两组大鼠死胎、血肿及肢体异常情况。观察阿糖胞苷诱导组大鼠骨组织形态变化。采用免疫印迹法和整体原位杂交法比较两组大鼠FGF4蛋白表达情况。比较两组大鼠氧化应激标志物[丙二醛(MDA)、谷胱甘肽(GSH)、超氧化物歧化酶(SOD)]和炎症因子[肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β和IL-6]基因相对表达量。结果:阿糖胞苷诱导组大鼠受孕后第7 天体重与对照组比较差异无统计学意义(P>0.05),第14、21天体重低于对照组(均P<0.05)。阿糖胞苷诱导组死胎、血肿和肢体异常比例高于对照组,但差异无统计学意义(均P>0.05)。大鼠胚胎成熟后,通过肢体外观和X射线图像可以观察到拇指的多指和并指畸形。免疫印迹结果显示,阿糖胞苷诱导组FGF4蛋白表达高于对照组(P<0.05)。整体原位杂交结果显示,阿糖胞苷诱导组FGF4染色强度高于对照组(P<0.05)。阿糖胞苷诱导组GSH和SOD低于对照组,MDA高于对照组(均P<0.05)。阿糖胞苷诱导组TNF-α、IL-1β和IL-6基因相对表达量高于对照组(均P<0.05)。结论:阿糖胞苷可诱导母鼠胚胎肢芽尖端FGF4的表达,增加氧化应激和炎症反应,进而引起胚胎肢芽发育异常,最终导致胎鼠先天性多指畸形。
Abstract:
Objective:To explore the expression of fibroblast growth factor 4(FGF4)in maternal rats induced by cytarabine and analyze the relationship with polydactyly in fetal rat.Methods: Sixteen female rats and eight male rats were mated in a ratio of 2 to 1.Rats were divided into control group(healthy pregnant rats,8 rats)and cytarabine-induced group(cytarabine was injected intraperitoneally at a dose of 100 mg/kg in the morning of the 11th day of pregnancy,8 rats).The weight of rats at different time points after pregnancy was compared between the two groups.The stillbirth,hematoma and limb abnormalities were compared between the two groups.The morphological change of bone tissue in cytarabine-induced rats was observed.The expression of FGF4 protein in the two groups was compared by Western blot and whole mount in situ hybridization.The relative expression of oxidative stress markers [malondialdehyde(MDA),glutathione(GSH),superoxide dismutase(SOD)] and inflammatory factors [tumor necrosis factor(TNF)-α,interleukin(IL)-1β and IL-6] genes were compared between the two groups.Results:There was no significant difference in body weight between cytarabine-induced group and control group on the 7th day of pregnancy(P>0.05),but the body weight on the 14th and 21st day was lower than that of control group(all P<0.05).The proportions of stillbirth,hematoma and limb abnormalities in the cytarabine-induced group were higher than those in the control group,but the differences were not statistically significant(all P>0.05).After maturation of rat embryos,polydactyly and syndactyly of the thumb can be observed through limb appearance and X-ray images.Immunoblotting showed that the expression of FGF4 protein in cytarabine-induced group was higher than that in control group(P<0.05).The results of whole mount in situ hybridization showed that the staining intensity of FGF4 in cytarabine-induced group was higher than that in control group(P<0.05).In the cytarabine-induced group,GSH and SOD were lower than those in the control group,and MDA was higher than those in the control group(all P<0.05).The relative expression of TNF-α,IL-1β and IL-6 genes in cytarabine-induced group were higher than those in the control group(all P<0.05).Conclusion:Cytarabine can induce the expression of FGF4 at the tip of limb bud of maternal rat embryo,increase oxidative stress and inflammation,and then cause abnormal development of limb bud of embryo,and finally lead to congenital polydactyly of fetal rat.

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备注/Memo

备注/Memo:
基金项目:陕西省卫生健康科研基金资助项目(2018D038)
更新日期/Last Update: 2022-06-06