不同剂量活血灵方对骨折后深静脉血栓的预防作用
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摘要
目的:探究中药方剂活血灵对骨折后下肢深静脉血栓的预防作用及其作用机制。方法:60只1月龄Wistar大鼠随机平均分成空白组,模型组,阳性药物组,活血灵低、中、高剂量组。采用创伤性造模方法制备大鼠骨折模型;各组在造模前1周灌胃,每天1次,连续14d;于造模后第7天取各组大鼠大隐静脉血栓测量重量,取各组大鼠腹腔血液检测凝血功能、生化法检测SOD、GSH-Px、MDA的含量。采用ELISA检测静脉组织、血清中炎症因子水平。结果:凝血检测,模型组较空白组的凝血时间缩短(P<0.01),阳性药物组、活血灵各剂量组凝血时间较模型组有所改善(P<0.05,P<0.01)。氧化应激检测,模型组与空白组SOD、GSH-Px、MDA含量比较,差异有统计学意义(P<0.01),阳性药物组、活血灵各剂量组与模型组比较,差异有统计学意义(P<0.05,P<0.01);炎症因子检测,模型组与空白组IL-1β、TNF-α含量比较,差异有统计学意义(P<0.01),阳性药物组、活血灵各剂量组IL-1β、TNF-α与模型组比较,差异有统计学意义(P<0.01)。结论:活血灵可通过改善凝血指标,减少血管内皮损伤抑制氧化应激反应及控制炎症,实现预防下肢深静脉血栓。
Objective: To explore prevention effect of Huoxueling formula(HXL) on venous thrombosis of lower limb after fracture and its possible mechanism. Methods: Sixty one-month-old wistar rats were randomly divided into blank group, model group, positive drug group, and HXL low, middle and high dose groups. The fracture model of rats was prepared by the method of traumatic modeling. Each group was intragastric administration once a day for 14 consecutive days, before the model was established. On the 7 th day after modeling, the weight of the great saphenous vein thrombosis in each group was measured, and the peritoneal blood of each group was used to detect coagulation function and biochemical method was used to detect the contents of SOD, GSH-Px and MDA. The levels of inflammatory factors in vein tissue and serum were detected by ELISA. Results: Coagulation test: The clotting time of the model group was shorter than that of the blank group(P<0.01). The clotting time of the positive drug group, the HXL groups were improved compared with the model group(P<0.05, P<0.01). Oxidative stress test: The contents of SOD, GSH-Px was decreased, while the MDA was increased in the model group compared with the blank group(P<0.01). The three indexes of the positive drug group, HXL groups were improved compared with the model group(P<0.01). Inflammatory factors detection: The contents of IL-1β and TNF-α in the model group were increased compared with the blank group(P<0.01). The contents of IL-1β and TNF-α in the positive drug group, HXL groups were improved compared with the model group(P<0.01). Conclusion: HXL can prevent deep venous thrombosis of lower limb, by improving the blood coagulation index, reducing the vascular endothelial injury inhibited oxidative stress respond and controlling inflammation.
Objective: To explore prevention effect of Huoxueling formula(HXL) on venous thrombosis of lower limb after fracture and its possible mechanism. Methods: Sixty one-month-old wistar rats were randomly divided into blank group, model group, positive drug group, and HXL low, middle and high dose groups. The fracture model of rats was prepared by the method of traumatic modeling. Each group was intragastric administration once a day for 14 consecutive days, before the model was established. On the 7 th day after modeling, the weight of the great saphenous vein thrombosis in each group was measured, and the peritoneal blood of each group was used to detect coagulation function and biochemical method was used to detect the contents of SOD, GSH-Px and MDA. The levels of inflammatory factors in vein tissue and serum were detected by ELISA. Results: Coagulation test: The clotting time of the model group was shorter than that of the blank group(P<0.01). The clotting time of the positive drug group, the HXL groups were improved compared with the model group(P<0.05, P<0.01). Oxidative stress test: The contents of SOD, GSH-Px was decreased, while the MDA was increased in the model group compared with the blank group(P<0.01). The three indexes of the positive drug group, HXL groups were improved compared with the model group(P<0.01). Inflammatory factors detection: The contents of IL-1β and TNF-α in the model group were increased compared with the blank group(P<0.01). The contents of IL-1β and TNF-α in the positive drug group, HXL groups were improved compared with the model group(P<0.01). Conclusion: HXL can prevent deep venous thrombosis of lower limb, by improving the blood coagulation index, reducing the vascular endothelial injury inhibited oxidative stress respond and controlling inflammation.
引文
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[7]于明薇,杨国旺,王笑民.化瘀丸联合化疗对小鼠Lewis肺癌生长及血栓形成相关因子的影响.中华中医药杂志,2012,27(12):3179-3183
[8]沈素红,郭艳幸,席占国,等.洛阳正骨传统方药活血灵预防骨科术后下肢深静脉血栓形成的临床研究.中国中医骨伤科杂志,2011,19(3):21-22
[9]赵学凌,吴雪梅,王兵,等.大鼠创伤性肢体深静脉血栓形成新型动物模型的建立.昆明医学院学报,2005(1):4-8
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[11]JoséA Diaz AEH,Christine M Alvarado,Alexandra M Berguer,et al.Thrombogenesis with continuous blood flow in the inferior vena cava.Thrombosis&Haemostasis,2010,104(2):366-375
[12]Ji Y Q,Feng M,Zhang Z H,et al.Varied response of the pulmonary arterial endothelium in a novel rat model of venous thromboembolism.Chinese Medical Journal,2013,126(1):114-117
[13]Aghourian M N,LemariéC A,Blostein M D.In vivo monitoring of venous thrombosis in mice.Journal of Thrombosis&Haemostasis,2012,10(3):447-452
[14]Cooley B C,Szema L,Chen C Y,et al.A murine model of deep vein thrombosis:characterization and validation in transgenic mice.Thrombosis&Haemostasis,2005,94(3):498-503
[15]G eier B,Muthwerthmann D,Barbera L,et al.Laparoscopic ligation of the infrarenal vena cava in combination with transfemoral thrombin infusion:a new animal model of chronic deep venous thrombosis.European Journal of Vascular&Endovascular Surgery the Official Journal of the European Society for Vascular Surgery,2005,29(5):542-548
[16]Brandt M,Sch?nfelder T,Schwenk M,et al.Deep vein thrombus formation induced by flow reduction in mice is determined by venous side branches.Clinical Hemorheology&Microcirculation,2014,56(2):145-152
[17]李润平,曹永兵,张汉明,等.三七总皂甙和银杏叶提取物预防急性氧中毒的实验研究.中国应用生理学杂志,2004(2):98-101
[18]Lubos E,Handy D E,Loscalzo J.Role of oxidative stress and nitric oxide in atherothrombosis.Frontiers in Bioscience A Journal&Virtual Library,2008,13(5):5323
[19]Eguchi Y,Takahari Y,Higashijima N,et al.Nicorandil attenuates FeCl(3)-induced thrombus formation through the inhibition of reactive oxygen species production.Circulation Journal Official Journal of the Japanese Circulation Society,2009,73(3):554-561
[20]De M R,Hoeth M,Hofer-Warbinek R,et al.The transcription factor NF-kappa B and the regulation of vascular cell function.Arteriosclerosis Thrombosis&Vascular Biology,2000,20(11):E83
[21]Ishibashi T.Molecular Hydrogen:New antioxidant and antiinflammatory therapy for rheumatoid arthritis and related diseases.Current Pharmaceutical Design,2013,19(35):6375-6381
[2]Heit JA,O’Fallon W M,Petterson T M,et al.Relative impact of risk factors for deep vein thrombosis and pulmonary embolism:A population-based study.Archives of Internal Medicine,2002,162(11):1245
[3]Eikelboom J W,Quinlan D J,Douketis J D.Extended-duration prophylaxis against venous thromboembolism after total hip or knee replacement:a meta-analysis of the randomised trials.Lancet,2001,358(9275):9-15
[4]Day S M,Reeve J L,Pedersen B,et al.Macrovascular thrombosis is driven by tissue factor derived primarily from the blood vessel wall.Blood,2005,105(1):192-198
[5]Ekim M,ekeroglu M R,Balahoroglu R,et al.Roles of the oxidative stress and ADMA in the development of deep venous thrombosis.Biochemistry Research International,2014,2014(2014):703128
[6]郭齐,赵乐,郝伟,等.牡丹皮有效组分重组方对大鼠体外血栓形成及血液流变学的影响.中华中医药杂志,2010,25(2):231-233
[7]于明薇,杨国旺,王笑民.化瘀丸联合化疗对小鼠Lewis肺癌生长及血栓形成相关因子的影响.中华中医药杂志,2012,27(12):3179-3183
[8]沈素红,郭艳幸,席占国,等.洛阳正骨传统方药活血灵预防骨科术后下肢深静脉血栓形成的临床研究.中国中医骨伤科杂志,2011,19(3):21-22
[9]赵学凌,吴雪梅,王兵,等.大鼠创伤性肢体深静脉血栓形成新型动物模型的建立.昆明医学院学报,2005(1):4-8
[10]Zhou J,May L,Liao P,et al.Inferior vena cava ligation rapidly induces tissue factor expression and venous thrombosis in rats.Arteriosclerosis Thrombosis&Vascular Biology,2009,29(6):863
[11]JoséA Diaz AEH,Christine M Alvarado,Alexandra M Berguer,et al.Thrombogenesis with continuous blood flow in the inferior vena cava.Thrombosis&Haemostasis,2010,104(2):366-375
[12]Ji Y Q,Feng M,Zhang Z H,et al.Varied response of the pulmonary arterial endothelium in a novel rat model of venous thromboembolism.Chinese Medical Journal,2013,126(1):114-117
[13]Aghourian M N,LemariéC A,Blostein M D.In vivo monitoring of venous thrombosis in mice.Journal of Thrombosis&Haemostasis,2012,10(3):447-452
[14]Cooley B C,Szema L,Chen C Y,et al.A murine model of deep vein thrombosis:characterization and validation in transgenic mice.Thrombosis&Haemostasis,2005,94(3):498-503
[15]G eier B,Muthwerthmann D,Barbera L,et al.Laparoscopic ligation of the infrarenal vena cava in combination with transfemoral thrombin infusion:a new animal model of chronic deep venous thrombosis.European Journal of Vascular&Endovascular Surgery the Official Journal of the European Society for Vascular Surgery,2005,29(5):542-548
[16]Brandt M,Sch?nfelder T,Schwenk M,et al.Deep vein thrombus formation induced by flow reduction in mice is determined by venous side branches.Clinical Hemorheology&Microcirculation,2014,56(2):145-152
[17]李润平,曹永兵,张汉明,等.三七总皂甙和银杏叶提取物预防急性氧中毒的实验研究.中国应用生理学杂志,2004(2):98-101
[18]Lubos E,Handy D E,Loscalzo J.Role of oxidative stress and nitric oxide in atherothrombosis.Frontiers in Bioscience A Journal&Virtual Library,2008,13(5):5323
[19]Eguchi Y,Takahari Y,Higashijima N,et al.Nicorandil attenuates FeCl(3)-induced thrombus formation through the inhibition of reactive oxygen species production.Circulation Journal Official Journal of the Japanese Circulation Society,2009,73(3):554-561
[20]De M R,Hoeth M,Hofer-Warbinek R,et al.The transcription factor NF-kappa B and the regulation of vascular cell function.Arteriosclerosis Thrombosis&Vascular Biology,2000,20(11):E83
[21]Ishibashi T.Molecular Hydrogen:New antioxidant and antiinflammatory therapy for rheumatoid arthritis and related diseases.Current Pharmaceutical Design,2013,19(35):6375-6381