甘油果糖对宫内窘迫胎鼠保护作用的研究
摘要
目的:研究甘油果糖注射液对宫内缺氧缺血胎鼠脑组织自由基和细胞凋亡的影响,探讨甘油果糖对宫内窘迫胎鼠脑组织的保护作用。
方法:WiStay雌性大白鼠,于妊娠第19d通过无损伤动脉钳钳夹双侧子宫、卵巢血管20min建立缺血缺氧宮内窘迫模型。孕鼠随机分为假手术组(A组),缺血缺氧组(B组),甘油果糖治疗组(3.5ml/100g,腹腔注射):甘油果糖HI前30min治疗组(C组)和HI后立即治疗组(D组)。此后实验用母鼠均关腹放回原饲养环境中24h后,立即剖宮取胎,确定胎鼠是否存活,在每组存活胎鼠中随机抽取10只断头取脑,以比色法测定脑组织丙二醛(MDA)含量、TUNEL法观察脑海马区神经元凋亡。
结果:
1、与缺血缺氧组比较,C组、D组胎鼠死亡率明显降低(P＜0.05,P＜0.05)。
2、与缺血缺氧组比较,C组、D组脑组织MDA含量降低(P＜0.01,P＜0.05);与D组比较,C组脑组织MDA含量降低(P＜0.01)。
3、与假手术组比较,缺血缺氧组脑海马神经元凋亡数目明显增加(P＜0.01)。C组、D组与缺血缺氧组比较,海马区凋亡细胞数目减少(P＜0.01,P＜0.05)。C组凋亡细胞数目多于D组(P＜0.01)。
结论:
1、钳夹孕鼠子宫、卵巢血管造成胎鼠缺氧缺血模型是模仿临床围生期胎儿窘迫较为理想的动物模型。
2、实验证明甘油果糖能够通过胎盘屏障及血脑屏障,可能通过促进能量代谢途径对HIBD胎鼠起脑保护作用。甘油果糖是否可以通过直接清除自由基对HIBD起治疗作用需进一步研究探讨。
3、实验表明缺氧缺血性脑损伤前用药比其后用药效果更佳.
Objective: To study the effects of Glycerol Fructose on free radical andapoptosis of fetal rat brain sufered from intrauterine hypoxic-ischemicinjury,so as to explore the neuroprotective mechanisms of GlycerolFructose.
Methods: Wistar female rats of gravidity were randomly divided into fourgoups : ham operation group ( group A ) , HI group(group B), GlycerolFructose-treated group (3.5ml/100g, intraperitoneal injection) : GlycerolFructose-treated ahead of HI(group C) , Glycerol Fructose-treatedimmediately after HI (group D). On the nineteenth day after gravidity , wemade the model of fetal rat distress by clamping the maternal uterine andovarian vessels in group B、C、D. The rats in group C were given GlycerolFructose 30 min ahead of HI, the rats in group D were given Glycerol Fructoseimmediately after HI. Group A was sham operated.The rats were made dead at24h after HI by cutting head and brain tissues were separately taken .Wejudged whether the fetal rats living or not , chose ten fetal rats randomlyeach group and measured the content of MDA in fetal brains and detectedthe number of hippocampus apoptosis .
Results :
1、The mortality rate of group C and D decreased significantly than thatof HI group (P<0. 05, P<0. 05).
2、The content of brain tissue MDA in group C and D decreased significantlythan that of HI group (P< 0.01, P<0. 05). MDA in group D increasedsignificantly, higher than that of group C (P<0. 01).
3、The number of hippocampus apoptosis in HI group increased significantlythan that of ham operation group (P<0.01) .The number of cerebralhippocampus apoptosis in group C and D decreased significantly than thatof HI group (P<0. 01, P<0. 05). Group C and D were significantly different (P<0. 01).
Conclusions :
1、It may be an ideal method to made the model of fetal rat distress byclamping the maternal uterine and ovarian vessels.
2、Glycerol Fructose can pass placental barrier and hematoencephalicbarrier, Glycerol Fructose may protect brain by promoting energy metabolism.Whether Glycerol Fructose can protect brain by cleaning up free radicaldirectly, more research is needed.
3、Preventive medication before HIBD is better than medicine interventionafter HIBD .
方法:WiStay雌性大白鼠,于妊娠第19d通过无损伤动脉钳钳夹双侧子宫、卵巢血管20min建立缺血缺氧宮内窘迫模型。孕鼠随机分为假手术组(A组),缺血缺氧组(B组),甘油果糖治疗组(3.5ml/100g,腹腔注射):甘油果糖HI前30min治疗组(C组)和HI后立即治疗组(D组)。此后实验用母鼠均关腹放回原饲养环境中24h后,立即剖宮取胎,确定胎鼠是否存活,在每组存活胎鼠中随机抽取10只断头取脑,以比色法测定脑组织丙二醛(MDA)含量、TUNEL法观察脑海马区神经元凋亡。
结果:
1、与缺血缺氧组比较,C组、D组胎鼠死亡率明显降低(P＜0.05,P＜0.05)。
2、与缺血缺氧组比较,C组、D组脑组织MDA含量降低(P＜0.01,P＜0.05);与D组比较,C组脑组织MDA含量降低(P＜0.01)。
3、与假手术组比较,缺血缺氧组脑海马神经元凋亡数目明显增加(P＜0.01)。C组、D组与缺血缺氧组比较,海马区凋亡细胞数目减少(P＜0.01,P＜0.05)。C组凋亡细胞数目多于D组(P＜0.01)。
结论:
1、钳夹孕鼠子宫、卵巢血管造成胎鼠缺氧缺血模型是模仿临床围生期胎儿窘迫较为理想的动物模型。
2、实验证明甘油果糖能够通过胎盘屏障及血脑屏障,可能通过促进能量代谢途径对HIBD胎鼠起脑保护作用。甘油果糖是否可以通过直接清除自由基对HIBD起治疗作用需进一步研究探讨。
3、实验表明缺氧缺血性脑损伤前用药比其后用药效果更佳.
Objective: To study the effects of Glycerol Fructose on free radical andapoptosis of fetal rat brain sufered from intrauterine hypoxic-ischemicinjury,so as to explore the neuroprotective mechanisms of GlycerolFructose.
Methods: Wistar female rats of gravidity were randomly divided into fourgoups : ham operation group ( group A ) , HI group(group B), GlycerolFructose-treated group (3.5ml/100g, intraperitoneal injection) : GlycerolFructose-treated ahead of HI(group C) , Glycerol Fructose-treatedimmediately after HI (group D). On the nineteenth day after gravidity , wemade the model of fetal rat distress by clamping the maternal uterine andovarian vessels in group B、C、D. The rats in group C were given GlycerolFructose 30 min ahead of HI, the rats in group D were given Glycerol Fructoseimmediately after HI. Group A was sham operated.The rats were made dead at24h after HI by cutting head and brain tissues were separately taken .Wejudged whether the fetal rats living or not , chose ten fetal rats randomlyeach group and measured the content of MDA in fetal brains and detectedthe number of hippocampus apoptosis .
Results :
1、The mortality rate of group C and D decreased significantly than thatof HI group (P<0. 05, P<0. 05).
2、The content of brain tissue MDA in group C and D decreased significantlythan that of HI group (P< 0.01, P<0. 05). MDA in group D increasedsignificantly, higher than that of group C (P<0. 01).
3、The number of hippocampus apoptosis in HI group increased significantlythan that of ham operation group (P<0.01) .The number of cerebralhippocampus apoptosis in group C and D decreased significantly than thatof HI group (P<0. 01, P<0. 05). Group C and D were significantly different (P<0. 01).
Conclusions :
1、It may be an ideal method to made the model of fetal rat distress byclamping the maternal uterine and ovarian vessels.
2、Glycerol Fructose can pass placental barrier and hematoencephalicbarrier, Glycerol Fructose may protect brain by promoting energy metabolism.Whether Glycerol Fructose can protect brain by cleaning up free radicaldirectly, more research is needed.
3、Preventive medication before HIBD is better than medicine interventionafter HIBD .
引文
[1]乐杰主编.妇产科学[M],第6版.北京:人民卫生出版社,2005.48
[2]韩田骏.胎儿窘迫程度与新生儿预后关系探讨[M].广东医学,1999,20(6):458-459.
[3]邹继珍,胡岚,吴莎等.围产儿宫内窘迫的临床病理分析[M].中华围产医学杂志,2004,7(3):142-144
[4]毕红杰.49例胎儿宫内窘迫临床分析.新医学导刊,2008,7(3):43-44
[5]虞人杰,李黎,汤泽中.新生儿窒息多器官损害的临床研究.中华儿科杂志,1997,35(3):138-141
[6]Martinancel A,Carciaalix H,Cabanas FGF,et al.Multiplen involvement in perinatal asphyxia.J Pediatr,1995,12(?):786
[7]赵振河等.头部敷贴式亚低温对新生鼠缺氧缺血性脑损伤时脑组织内一氧化氮和丙二醛含量的影响.中国妇幼保健,2008,25(23):3587-3589
[8]苏浩彬,郑念时,陈琴.新生儿HIE血清SOD活性和MDA浓度变化及临床意义.中国优生与遗传杂志,2000,8(4):20-21
[9]陈广斌,陈华萍等.芍药苷对缺氧缺血性脑损伤新生大鼠脑组织丙二醛、超氧化物歧化酶的影响,实用儿科临床杂志,2008,23(16):1272-1273
[10]俞丹,毛萌,周晖等.宫内缺血缺氧致胚鼠脑细胞损伤凋亡的实验研究[J].四川大学学报(医学版),2004,35(3):354-357
[11]王乔,曾庆云等.TUNEL法原位检测凋亡细胞的某些改进.武汉大学学报,2001,22(3):283-284
[12]金汉珍,黄德双,官希古.实用新生儿学,第二版.北京:人民卫生出版社,2000:624-31
[13]薄涛,严超英,李巍等.结扎孕鼠双侧子宫动脉复制围产期缺氧缺血性脑损伤动物模型.中风与神经疾病杂志,2001,18(1):40-41
[14]Delivoria PM,Mishra OP.Mechainsms of cerebral injury in perinatal asphyxia and strategies for prevention[M].J Pediatr,1998,132:30-34.
[15]王万铁,徐正介,李东等.心肌缺血再灌注损伤时MAP与MDA的相关分 析.温州医学院学报,1997,27:76-78.
[16]Li Y,Sharov VG,Jiang N,et al.Ultrastructural and light microscopic evidence of apoptosis after middle cerebral artery occlusion in the rat[J],Am J Pathol,1995,146:1045-1051
[17]Dell AE,Chen Y,Engidawork E,etal Delayed neuronal death following perinatal asphxia in rat[J].Exp Brain Res,1997.115:105-115
[18]Charriam-Marlangue C,Margaill I,Represa A.et al.Apoptosis and necrosis after reversible focal ischemia,an in situ DNA fragementation analysis[J]J Cereb Blood Flow Metab 1996,16(2):186-194
[19]Cheng Y.Deshmukh MD.Costa A.el al.Caspase inhibitor afords neuroprotection with delayed administration in a rat model of neonatal hypoxic-ischermia brain injury[J]J Clin Invest,1998,101:1992-1999
[20]黄广.新生大鼠缺氧缺血性脑损伤后细胞凋亡与自由基损伤机制研究.河北医学,2008,14(3):255-256
[21]Hill IE,MacmanusJ P,Rasquinha I.etal.DNA fragmentation indicative of apoptosis following unilateral cerebral hypoxic -ischemia in the neonatal rat.Brain Research,1995,676:398-403
[22]Sidhu RS,Tuor UI,Bigio MR.et al.Nuclear condensation and fr augmentation following cerebral hypoxia-ischemia occurs more frequently in immature than older rats Neurosci Lett,1997;223:129-132
[23]Vannucci SJ,reinhartR,MaherF,et al.Alterations in GLUT1 and GLUT3 glucose transporter gene expression following unilateral hypoxia-ischemia in the immature rat brain[J].Brain Res Dev Brain Res,1998,107:155-264
[24]Bagenholm R,Nilsson UA,Kjellmer I.Formation of free radicals in hypoxic ischemic brain damage in the neonatal rat [J].Brain.Res,1997,773:132-138。
[25]Meada M.Meada M Analysis of oxidative in rat fetus induced by clamping and reperfusion of uterine vessels.Nippon sanka Fajinka Gakkai zassni,1996,48:111-117
[26]Baqenholm R,Nilssom UA,Gotborq CW,etal.Free radicals are formed in the brain of fetal sheep during reperfusion after cerebrad ischemia,pediatr Res,1998,43:271-275。
[27]宋薇薇,韩玉昆,尚涛.宫内窘迫胎鼠脑及肝组织自由基损伤的研究.中华妇产科杂志,1999,34(8):473-475。
[28]谢集建,扬勇,陈宝芳.缺血缺氧性脑损伤的发病机理研究进展.国外医学妇幼保健分册,2002,13(1):30-32。
[29]陈惠金.新生儿缺氧缺血性脑病的发病机制和防治进展.实用儿科临床杂志,1999:14(4):233-235
[30]赵晓晖,顾承志,黄怀宇,黄志东.甘油果糖对急性脑出血血液流变性及微循环的影响.中国微循环,2003,7(6):373-374
[1]张祥建,李翠宁.甘油果糖对人RBC、大鼠RBC的作用及输液安全性的研究.脑与神经疾病杂志,2004.12(2):91-96
[2]Bereczki D,Mihalka,DL.Szatmari S,et al.Mannitol use acute Stroke:case fatality at 30 days and 1 year.Stroke,2003,34:1730-1735
[3]Frank M S,Nahata MC,Hilty MD.a review of its pharmacology,Pharmacokinetics,adverse reactions and clinical use pharmacotherapy[J].Pharmacotherapy,1998,1(2):147-160
[4]Tsubokawa T,Katayama Y,Ishii S.Fructose-added glycerol for therapy of elevated intracranial pressure:analysis of the side effects of long-term administration in a multi-institutional trial [M];Neurological Research;1989年
[5]赵晓晖,顾承志.甘油果糖对急性脑出血血液流变性及微循环的影响.中国微循环,2003.7(6):373-374
[6]坪川孝志,石井昌三.Glycerol注射专用连续投与の临床效果.新药と临床.1986,35(2):134-140
[7]杨树源,岳勇.甘油果糖注射液降低颅内压的临床.中华神经外科杂志,1994,10(5):272-274
[8]野田行文,高野,铃木成生.Glycerol头盖内压下降作用.新药と临床,1977,26:175
[9]徐新,刘云。甘油果糖对血糖和胰岛素水平影响的临床观察.交通医学,2006.20(6):740
[10]班显明.甘油果糖与甘露醇联合治疗急性脑卒中高颅压的疗效观察.医学文选,2005.24(6):929-930
[11]施建生,樊兴娟.甘露醇和甘油果糖联合治疗脑出血临床研究.江苏医药,2000,30(5):368-369
[12]Qian DX.Huang DJ.He BW Effects of glycerin and fructose injection on hemorrheological properties after brain injuries [J].Chin J New Drug Rein,2000,19(5):359-363.
[13]于洪,刘昌义,宋本华.甘油果糖注射液治疗急性脑血管病的临床观察.齐齐哈尔医学院学报,2001.22(8):901
[14]范大公,赵伟.甘油果糖注射液和甘露醇用于缺血性脑梗死的比较研究.齐齐哈尔医学院学报,2002,23(7):754
[15]李群彦.甘油果糖注射液和甘露醇用于缺血性中风的比较研究[J].脑与神经疾病杂志,2001,9(5):313
[16]马春芳,李丽.七叶皂苷联合甘油果糖治疗跟骨骨折致关节肿胀疗效分析.中国药师,2008.11(4):445-446
[17]刘和亮,赵金垣.甘油果糖注射液对急性肺损伤治疗作用的实验研究.中国预防医学杂志,2001.2(1):22-25
[18]杨树源,岳勇.甘油果糖注射液降低颅内压的临床.中华神经外科杂志,1994,10(5):272-274
[19]野田行文,高野,铃木成生.Glycerol头盖内压下降作用.新药と临床,1977,26:175
[20]陈以翔,刘开明.纳络酮联合甘油果糖治疗尼尔氏病40例临床分析.Chinese journal of practical Chinese with modern medicine,2005VOL.(18) N0.23:1796
[21]伊藤义彰.抗脑水肿药[J],日本医学介绍,1998:(1):20.
[22]何冬英.甘油果糖治疗急性梅尼埃病32例临床分析[J].医学理论与实践,2000,13(9):527
[23]史铭宇,曹军.甘油果糖与甘露醇眼科应用观察.中国实用眼科杂志,2006.24(8):20-821
[24]闰惠青,黄高秀.两种降低青光眼眼压药物的效果比较.广西医学,2008.30(1):39-40
[25]李忠,赵继宗.甘油果糖治疗椎管肿瘤术后脊髓水肿临床效果观察.中华现代中函医杂志,2005.3(9):792
[26]Rash JE.Yasumura T.Hudson CS.Direct immunogold labeling aquaporin 4 in square arrays of astrocyte and ependymocyte plasma membranes in rat brain and spinal cord.Proc Natl Acad Sci USA.1998,95(20):11981-11986.
[27]李菊明.腰椎退变性疾患术后脱水剂的应用.现代中西医结合杂志,2008,17(33):5157-5158
[28]余庆宪,袁耀宗.甘油果糖在结肠镜检查前肠道清洁中的应用.中国消化内镜杂志,2001.18(5):309
[29]申颖,白莺,金旭,王保国.甘油果糖复合神经阻滞治疗颈源性头痛的临床观察.中国康复理论与实践,2008.14(6):506-507
[30]田力,梁靓靓.甘露醇和甘油果糖对脑出血患者肾功能损害的临床观察[J].中国老年学杂志,2007,3(27):479-480.
[2]韩田骏.胎儿窘迫程度与新生儿预后关系探讨[M].广东医学,1999,20(6):458-459.
[3]邹继珍,胡岚,吴莎等.围产儿宫内窘迫的临床病理分析[M].中华围产医学杂志,2004,7(3):142-144
[4]毕红杰.49例胎儿宫内窘迫临床分析.新医学导刊,2008,7(3):43-44
[5]虞人杰,李黎,汤泽中.新生儿窒息多器官损害的临床研究.中华儿科杂志,1997,35(3):138-141
[6]Martinancel A,Carciaalix H,Cabanas FGF,et al.Multiplen involvement in perinatal asphyxia.J Pediatr,1995,12(?):786
[7]赵振河等.头部敷贴式亚低温对新生鼠缺氧缺血性脑损伤时脑组织内一氧化氮和丙二醛含量的影响.中国妇幼保健,2008,25(23):3587-3589
[8]苏浩彬,郑念时,陈琴.新生儿HIE血清SOD活性和MDA浓度变化及临床意义.中国优生与遗传杂志,2000,8(4):20-21
[9]陈广斌,陈华萍等.芍药苷对缺氧缺血性脑损伤新生大鼠脑组织丙二醛、超氧化物歧化酶的影响,实用儿科临床杂志,2008,23(16):1272-1273
[10]俞丹,毛萌,周晖等.宫内缺血缺氧致胚鼠脑细胞损伤凋亡的实验研究[J].四川大学学报(医学版),2004,35(3):354-357
[11]王乔,曾庆云等.TUNEL法原位检测凋亡细胞的某些改进.武汉大学学报,2001,22(3):283-284
[12]金汉珍,黄德双,官希古.实用新生儿学,第二版.北京:人民卫生出版社,2000:624-31
[13]薄涛,严超英,李巍等.结扎孕鼠双侧子宫动脉复制围产期缺氧缺血性脑损伤动物模型.中风与神经疾病杂志,2001,18(1):40-41
[14]Delivoria PM,Mishra OP.Mechainsms of cerebral injury in perinatal asphyxia and strategies for prevention[M].J Pediatr,1998,132:30-34.
[15]王万铁,徐正介,李东等.心肌缺血再灌注损伤时MAP与MDA的相关分 析.温州医学院学报,1997,27:76-78.
[16]Li Y,Sharov VG,Jiang N,et al.Ultrastructural and light microscopic evidence of apoptosis after middle cerebral artery occlusion in the rat[J],Am J Pathol,1995,146:1045-1051
[17]Dell AE,Chen Y,Engidawork E,etal Delayed neuronal death following perinatal asphxia in rat[J].Exp Brain Res,1997.115:105-115
[18]Charriam-Marlangue C,Margaill I,Represa A.et al.Apoptosis and necrosis after reversible focal ischemia,an in situ DNA fragementation analysis[J]J Cereb Blood Flow Metab 1996,16(2):186-194
[19]Cheng Y.Deshmukh MD.Costa A.el al.Caspase inhibitor afords neuroprotection with delayed administration in a rat model of neonatal hypoxic-ischermia brain injury[J]J Clin Invest,1998,101:1992-1999
[20]黄广.新生大鼠缺氧缺血性脑损伤后细胞凋亡与自由基损伤机制研究.河北医学,2008,14(3):255-256
[21]Hill IE,MacmanusJ P,Rasquinha I.etal.DNA fragmentation indicative of apoptosis following unilateral cerebral hypoxic -ischemia in the neonatal rat.Brain Research,1995,676:398-403
[22]Sidhu RS,Tuor UI,Bigio MR.et al.Nuclear condensation and fr augmentation following cerebral hypoxia-ischemia occurs more frequently in immature than older rats Neurosci Lett,1997;223:129-132
[23]Vannucci SJ,reinhartR,MaherF,et al.Alterations in GLUT1 and GLUT3 glucose transporter gene expression following unilateral hypoxia-ischemia in the immature rat brain[J].Brain Res Dev Brain Res,1998,107:155-264
[24]Bagenholm R,Nilsson UA,Kjellmer I.Formation of free radicals in hypoxic ischemic brain damage in the neonatal rat [J].Brain.Res,1997,773:132-138。
[25]Meada M.Meada M Analysis of oxidative in rat fetus induced by clamping and reperfusion of uterine vessels.Nippon sanka Fajinka Gakkai zassni,1996,48:111-117
[26]Baqenholm R,Nilssom UA,Gotborq CW,etal.Free radicals are formed in the brain of fetal sheep during reperfusion after cerebrad ischemia,pediatr Res,1998,43:271-275。
[27]宋薇薇,韩玉昆,尚涛.宫内窘迫胎鼠脑及肝组织自由基损伤的研究.中华妇产科杂志,1999,34(8):473-475。
[28]谢集建,扬勇,陈宝芳.缺血缺氧性脑损伤的发病机理研究进展.国外医学妇幼保健分册,2002,13(1):30-32。
[29]陈惠金.新生儿缺氧缺血性脑病的发病机制和防治进展.实用儿科临床杂志,1999:14(4):233-235
[30]赵晓晖,顾承志,黄怀宇,黄志东.甘油果糖对急性脑出血血液流变性及微循环的影响.中国微循环,2003,7(6):373-374
[1]张祥建,李翠宁.甘油果糖对人RBC、大鼠RBC的作用及输液安全性的研究.脑与神经疾病杂志,2004.12(2):91-96
[2]Bereczki D,Mihalka,DL.Szatmari S,et al.Mannitol use acute Stroke:case fatality at 30 days and 1 year.Stroke,2003,34:1730-1735
[3]Frank M S,Nahata MC,Hilty MD.a review of its pharmacology,Pharmacokinetics,adverse reactions and clinical use pharmacotherapy[J].Pharmacotherapy,1998,1(2):147-160
[4]Tsubokawa T,Katayama Y,Ishii S.Fructose-added glycerol for therapy of elevated intracranial pressure:analysis of the side effects of long-term administration in a multi-institutional trial [M];Neurological Research;1989年
[5]赵晓晖,顾承志.甘油果糖对急性脑出血血液流变性及微循环的影响.中国微循环,2003.7(6):373-374
[6]坪川孝志,石井昌三.Glycerol注射专用连续投与の临床效果.新药と临床.1986,35(2):134-140
[7]杨树源,岳勇.甘油果糖注射液降低颅内压的临床.中华神经外科杂志,1994,10(5):272-274
[8]野田行文,高野,铃木成生.Glycerol头盖内压下降作用.新药と临床,1977,26:175
[9]徐新,刘云。甘油果糖对血糖和胰岛素水平影响的临床观察.交通医学,2006.20(6):740
[10]班显明.甘油果糖与甘露醇联合治疗急性脑卒中高颅压的疗效观察.医学文选,2005.24(6):929-930
[11]施建生,樊兴娟.甘露醇和甘油果糖联合治疗脑出血临床研究.江苏医药,2000,30(5):368-369
[12]Qian DX.Huang DJ.He BW Effects of glycerin and fructose injection on hemorrheological properties after brain injuries [J].Chin J New Drug Rein,2000,19(5):359-363.
[13]于洪,刘昌义,宋本华.甘油果糖注射液治疗急性脑血管病的临床观察.齐齐哈尔医学院学报,2001.22(8):901
[14]范大公,赵伟.甘油果糖注射液和甘露醇用于缺血性脑梗死的比较研究.齐齐哈尔医学院学报,2002,23(7):754
[15]李群彦.甘油果糖注射液和甘露醇用于缺血性中风的比较研究[J].脑与神经疾病杂志,2001,9(5):313
[16]马春芳,李丽.七叶皂苷联合甘油果糖治疗跟骨骨折致关节肿胀疗效分析.中国药师,2008.11(4):445-446
[17]刘和亮,赵金垣.甘油果糖注射液对急性肺损伤治疗作用的实验研究.中国预防医学杂志,2001.2(1):22-25
[18]杨树源,岳勇.甘油果糖注射液降低颅内压的临床.中华神经外科杂志,1994,10(5):272-274
[19]野田行文,高野,铃木成生.Glycerol头盖内压下降作用.新药と临床,1977,26:175
[20]陈以翔,刘开明.纳络酮联合甘油果糖治疗尼尔氏病40例临床分析.Chinese journal of practical Chinese with modern medicine,2005VOL.(18) N0.23:1796
[21]伊藤义彰.抗脑水肿药[J],日本医学介绍,1998:(1):20.
[22]何冬英.甘油果糖治疗急性梅尼埃病32例临床分析[J].医学理论与实践,2000,13(9):527
[23]史铭宇,曹军.甘油果糖与甘露醇眼科应用观察.中国实用眼科杂志,2006.24(8):20-821
[24]闰惠青,黄高秀.两种降低青光眼眼压药物的效果比较.广西医学,2008.30(1):39-40
[25]李忠,赵继宗.甘油果糖治疗椎管肿瘤术后脊髓水肿临床效果观察.中华现代中函医杂志,2005.3(9):792
[26]Rash JE.Yasumura T.Hudson CS.Direct immunogold labeling aquaporin 4 in square arrays of astrocyte and ependymocyte plasma membranes in rat brain and spinal cord.Proc Natl Acad Sci USA.1998,95(20):11981-11986.
[27]李菊明.腰椎退变性疾患术后脱水剂的应用.现代中西医结合杂志,2008,17(33):5157-5158
[28]余庆宪,袁耀宗.甘油果糖在结肠镜检查前肠道清洁中的应用.中国消化内镜杂志,2001.18(5):309
[29]申颖,白莺,金旭,王保国.甘油果糖复合神经阻滞治疗颈源性头痛的临床观察.中国康复理论与实践,2008.14(6):506-507
[30]田力,梁靓靓.甘露醇和甘油果糖对脑出血患者肾功能损害的临床观察[J].中国老年学杂志,2007,3(27):479-480.