中华妇产科杂志
中華婦產科雜誌
중화부산과잡지
CHINESE JOUNAL OF OBSTETRICS AND GYNECOLOGY
2013年
12期
935-938
,共4页
血栓形成%雷洛昔芬%雌激素类,共扼(USP)%药物疗法,联合%阉割%大鼠
血栓形成%雷洛昔芬%雌激素類,共扼(USP)%藥物療法,聯閤%閹割%大鼠
혈전형성%뢰락석분%자격소류,공액(USP)%약물요법,연합%엄할%대서
Thrombosis%Raloxifene%Estrogens,conjugated (USP)%Drug therapy,combination%Castration%Rats
目的 通过去势建立绝经大鼠模型,将雷洛昔芬(RLX)与不同剂量的结合雌激素(CEE)配伍,观察两药联合应用对绝经大鼠血栓前状态的影响.方法 将64只9～10月龄的健康雌性SD大鼠随机分为4组,每组8只.手术去势后1周进行药物干预,给药10周后处死.对照组:给予安慰剂(0.9％氯化钠溶液灌胃);RLX组:给予RLX 6 rmg/(kg·d);CEE组:给予CEE 0.07 mg/(kg·d);RLX+低量CEE组:给予RLX6 mg/(kg·d)+CEE 0.07 mg/(kg·d);RLX+高量CEE组:给予RLX 6 mg/(kg·d)+CEE 0.5 mg/(kg·d).采用凝血酶比浊法检测各组大鼠血浆纤维蛋白原(FIB)含量;采用发射底物法检测抗凝血酶Ⅲ(ATⅢ)活性;采用ELISA双抗体夹心法检测纤溶酶原激活物抑制剂1(PAI-1)、D二聚体(D-D)、血管性假血友病因子(vWF)含量;采用硝酸还原酶法检测NO含量.结果 (1)凝血及抗凝血指标:对照组FIB含量为(1.62 +0.22) g/L、RLX组为(2.02±0.54) g/L、RLX+低量CEE组为(1.97 ±0.16)g/L、RLX+高量CEE组为(2.00 ±0.18) g/L,后3组分别与对照组比较,差异均有统计学意义(P＜0.05);但后3组间比较,差异无统计学意义(P＞0.05).血浆ATⅢ活性各组间比较,差异均无统计学意义(P＞0.05).(2)纤溶和抗纤溶指标:对照组PAI-1含量为(14.1±2.8)μg/L,RLX组为(20.0±3.3)μg/L,RLX+低量CEE组为(41.5±5.5)μg/L,RLX+高量CEE组为(38.9±6.0)μg/L,后3组分别与对照组比较,差异均有统计学意义(P＜0.05);但血浆D-D含量各组间比较,差异无统计学意义(P＞0.05).(3)血管内皮功能:对照组血浆vWF含量为(43±7)％,RLX组为(49±5)％,RLX+低量CEE组为(46±6)％,RLX+高量CEE组为(36±5)％,RLX+高量CEE组血浆vWF含量明显低于其他3组,差异也有统计学意义(P＜0.05).各组NO含量比较,差异无统计学意义(P＞0.05).结论 在血栓形成的不同环节,RLX发挥了不同的效应,可能导致血栓形成的风险增加.CEE在纤溶和抗纤溶方面与RLX具有协同作用,可进一步增加RLX的致血栓效应;在血管内皮功能方面则起到一定保护作用,然而这种效应需要高剂量CEE才能显现.
目的 通過去勢建立絕經大鼠模型,將雷洛昔芬(RLX)與不同劑量的結閤雌激素(CEE)配伍,觀察兩藥聯閤應用對絕經大鼠血栓前狀態的影響.方法 將64隻9～10月齡的健康雌性SD大鼠隨機分為4組,每組8隻.手術去勢後1週進行藥物榦預,給藥10週後處死.對照組:給予安慰劑(0.9％氯化鈉溶液灌胃);RLX組:給予RLX 6 rmg/(kg·d);CEE組:給予CEE 0.07 mg/(kg·d);RLX+低量CEE組:給予RLX6 mg/(kg·d)+CEE 0.07 mg/(kg·d);RLX+高量CEE組:給予RLX 6 mg/(kg·d)+CEE 0.5 mg/(kg·d).採用凝血酶比濁法檢測各組大鼠血漿纖維蛋白原(FIB)含量;採用髮射底物法檢測抗凝血酶Ⅲ(ATⅢ)活性;採用ELISA雙抗體夾心法檢測纖溶酶原激活物抑製劑1(PAI-1)、D二聚體(D-D)、血管性假血友病因子(vWF)含量;採用硝痠還原酶法檢測NO含量.結果 (1)凝血及抗凝血指標:對照組FIB含量為(1.62 +0.22) g/L、RLX組為(2.02±0.54) g/L、RLX+低量CEE組為(1.97 ±0.16)g/L、RLX+高量CEE組為(2.00 ±0.18) g/L,後3組分彆與對照組比較,差異均有統計學意義(P＜0.05);但後3組間比較,差異無統計學意義(P＞0.05).血漿ATⅢ活性各組間比較,差異均無統計學意義(P＞0.05).(2)纖溶和抗纖溶指標:對照組PAI-1含量為(14.1±2.8)μg/L,RLX組為(20.0±3.3)μg/L,RLX+低量CEE組為(41.5±5.5)μg/L,RLX+高量CEE組為(38.9±6.0)μg/L,後3組分彆與對照組比較,差異均有統計學意義(P＜0.05);但血漿D-D含量各組間比較,差異無統計學意義(P＞0.05).(3)血管內皮功能:對照組血漿vWF含量為(43±7)％,RLX組為(49±5)％,RLX+低量CEE組為(46±6)％,RLX+高量CEE組為(36±5)％,RLX+高量CEE組血漿vWF含量明顯低于其他3組,差異也有統計學意義(P＜0.05).各組NO含量比較,差異無統計學意義(P＞0.05).結論 在血栓形成的不同環節,RLX髮揮瞭不同的效應,可能導緻血栓形成的風險增加.CEE在纖溶和抗纖溶方麵與RLX具有協同作用,可進一步增加RLX的緻血栓效應;在血管內皮功能方麵則起到一定保護作用,然而這種效應需要高劑量CEE纔能顯現.
목적 통과거세건립절경대서모형,장뢰락석분(RLX)여불동제량적결합자격소(CEE)배오,관찰량약연합응용대절경대서혈전전상태적영향.방법 장64지9～10월령적건강자성SD대서수궤분위4조,매조8지.수술거세후1주진행약물간예,급약10주후처사.대조조:급여안위제(0.9％록화납용액관위);RLX조:급여RLX 6 rmg/(kg·d);CEE조:급여CEE 0.07 mg/(kg·d);RLX+저량CEE조:급여RLX6 mg/(kg·d)+CEE 0.07 mg/(kg·d);RLX+고량CEE조:급여RLX 6 mg/(kg·d)+CEE 0.5 mg/(kg·d).채용응혈매비탁법검측각조대서혈장섬유단백원(FIB)함량;채용발사저물법검측항응혈매Ⅲ(ATⅢ)활성;채용ELISA쌍항체협심법검측섬용매원격활물억제제1(PAI-1)、D이취체(D-D)、혈관성가혈우병인자(vWF)함량;채용초산환원매법검측NO함량.결과 (1)응혈급항응혈지표:대조조FIB함량위(1.62 +0.22) g/L、RLX조위(2.02±0.54) g/L、RLX+저량CEE조위(1.97 ±0.16)g/L、RLX+고량CEE조위(2.00 ±0.18) g/L,후3조분별여대조조비교,차이균유통계학의의(P＜0.05);단후3조간비교,차이무통계학의의(P＞0.05).혈장ATⅢ활성각조간비교,차이균무통계학의의(P＞0.05).(2)섬용화항섬용지표:대조조PAI-1함량위(14.1±2.8)μg/L,RLX조위(20.0±3.3)μg/L,RLX+저량CEE조위(41.5±5.5)μg/L,RLX+고량CEE조위(38.9±6.0)μg/L,후3조분별여대조조비교,차이균유통계학의의(P＜0.05);단혈장D-D함량각조간비교,차이무통계학의의(P＞0.05).(3)혈관내피공능:대조조혈장vWF함량위(43±7)％,RLX조위(49±5)％,RLX+저량CEE조위(46±6)％,RLX+고량CEE조위(36±5)％,RLX+고량CEE조혈장vWF함량명현저우기타3조,차이야유통계학의의(P＜0.05).각조NO함량비교,차이무통계학의의(P＞0.05).결론 재혈전형성적불동배절,RLX발휘료불동적효응,가능도치혈전형성적풍험증가.CEE재섬용화항섬용방면여RLX구유협동작용,가진일보증가RLX적치혈전효응;재혈관내피공능방면칙기도일정보호작용,연이저충효응수요고제량CEE재능현현.
Objective To study effects of raloxifene (RLX) with different doses of conjugated equine estrogen(CEE) on prothrombotic profiles in the ovariectomized rats model.Methods Total of 32healthy female SD rats at age of 9 to 10 months were equally divided into every 8 rats at 4 groups randomly.One week after ovariectomized,they were treated by drugs,including control group with placebo(0.9％ Nacl intragastric administration),RLX group with RLX 6 mg/(kg · d),RLX and low CEE group with RLX 6 mg/(kg · d) + CEE 0.07 mg/(kg · d)and RLX and high CEE group with RLX 6 mg/(kg · d) + CEE 0.5mg/(kg· d)for 10 weeks before death.Thrombin turbidimetry method was used to evaluate the plasma fibrinogen(FIB),transmitting substrate method for antithrombin Ⅲ (AT Ⅲ) activity,double-antibody sandwich ELISA for plasminogen activator inhibitor 1 (PAI-1),D-dimer (D-D) and yon Willebrand factor (vWF) and nitrate reductase method for nitric oxide(NO).Results (1) Coagulation and anticoagulation indicators:it was observed (1.62 ± 0.22) g/L FIB at control group,(2.02 0.54) g/L at RLX group,(1.97 ±0.16) g/L at RLX and low CEE group,(2.00 0.18) g/L at RLX and high CEE group.There was a statistically significant difference between control group and any one of treatment groups(P ＜ 0.05) and no statistical significance among those three treatment groups (P ＞ 0.05).No significant change was observed in plasma AT Ⅲ activity among groups (P ＞ 0.05).(2) Fibrinolytic and anti-fibrinolytic indicators:it was observed (14.1 2.8) μg/L PAI-1 at control group,(20.0 ±3.3) μg/L at RLX group,(41.5 ±5.5) μg/L at RLX and low CEE group,(38.9 ± 6.0) μg/L at RLX and high CEE group.A remarkable increase was observed between control group and any one of treatment groups(P ＜0.05).But there was no significant difference of D-D among groups (P ＞ 0.05).(3) Endothelial function:it was (43 ± 7) ％ vWF at control group,(49±5)％ at RLX group,(46±6)％ at RLX and low CEE group,(36±5)％ at RLX and high CEE group.The vWF of RLX and high CEE group was the lowest among all groups (P ＜0.05).There was no difference of NO among groups (P ＞ 0.05).Conclusions In the different links of thrombosis,RLX gives different fuction and may increase the risk.CEE plays a synergism role in the matter of fibrinolysis and anti-fibrinolysis with RLX,further giving rise to thrombosis effect of RLX.And it also has a protective role in the function of vascular endothelium to some extent.But this only works with high dose.
