丹参酮-ⅡA磺酸钠对脊髓缺血再灌注损伤NF-κB、VCAM-1和血液流变性的影响
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作者Author单位AddressE-Mail
张俐 ZHANG Li 福建中医药大学骨伤学院省部共建教育部重点实验室,福建 福州 350108 Key Laboratory of Ministry of Education of the People's Republic of China, School of Orthopaedics and Traumatology of TCM, Fujian University of Traditional Chinese Medicine, Fuzhou 351008, Fujian, China zhanglil626@163.com 
安国尧 AN Guo-yao 福建中医药大学骨伤学院省部共建教育部重点实验室,福建 福州 350108 Key Laboratory of Ministry of Education of the People's Republic of China, School of Orthopaedics and Traumatology of TCM, Fujian University of Traditional Chinese Medicine, Fuzhou 351008, Fujian, China  
张文光 ZHANG Wen-guang 福建中医药大学骨伤学院省部共建教育部重点实验室,福建 福州 350108 Key Laboratory of Ministry of Education of the People's Republic of China, School of Orthopaedics and Traumatology of TCM, Fujian University of Traditional Chinese Medicine, Fuzhou 351008, Fujian, China  
陈凯 CHEN Kai 福建中医药大学骨伤学院省部共建教育部重点实验室,福建 福州 350108 Key Laboratory of Ministry of Education of the People's Republic of China, School of Orthopaedics and Traumatology of TCM, Fujian University of Traditional Chinese Medicine, Fuzhou 351008, Fujian, China  
期刊信息:《中国骨伤》2012年,第25卷,第12期,第1016-1020页
DOI:10.3969/j.issn.1003-0034.2012.12.011
基金项目:国家自然科学基金(编号:30973765);国家新世纪人才支持计划(编号:NECT-09-0013);教育部博士点基金(编号:20113519110001)
中文摘要:

目的:观察丹参酮-ⅡA磺酸钠对脊髓缺血再灌注损伤关键因子核因子-κB (nuclear factor-kappaB,NF-κB)、血管细胞粘附分子-1(vascular cell adhesion molecule-1,VCAM-1)及血液流变性的影响,探讨该药对脊髓缺血再灌注损伤的作用及机制。

方法:选取3月龄新西兰家兔54只,体重为(2.0±0.2) kg,随机分为假手术组6只(术中仅分离腰动脉并于手术前后各0.5 h沿耳缘静脉注射生理盐水,0.8 ml/kg)、缺血组24只(分离后夹闭腰动脉,同上注射等剂量生理盐水)、丹参酮组24只(分离后夹闭腰动脉,同上注射等剂量丹参酮-ⅡA磺酸钠).分别于给药后0.5、1、4、8 h腹主动脉采血,用于检测全血粘度[高切(mpa.s)/150(l/s)、中切(mpa.s)/60(l/s)、低切(mpa.s)/10(l/s)]、毛细管血浆粘度、红细胞聚集指数、刚性指数、变形指数和电泳指数。同时取脊髓组织,分为两段,一段固定于4%的多聚甲醛中,另一段放入液氮中冻存,用免疫组化法和ELISA法检测3组各时点脊髓NF-κB、VCAM-1含量的变化。

结果:①脊髓缺血再灌注损伤后NF-κB表达,同一时点免疫组化图片中丹参酮组表达最少,缺血组中表达最高。②与假手术组相比,缺血组各时点VCAM-1表达显着升高,在0.5、1、4 h时差异显着(P<0.01),8 h时具有差异性(P<0.05);此外,丹参酮组与缺血组相比,0.5 h显着降低(P<0.01),1、4、8 h时降低且具有差异性(P<0.05).③假手术组始终无阳性血管表达,0.5 h缺血组、丹参酮组亦无阳性血管表达;1、4、8 h缺血组阳性血管表达率最高,其中1、4 h中丹参酮组与缺血组相比较差异显着(P<0.05),8 h差异显着(P<0.01).④缺血组各时点全血粘度在10 s-1、60 s-1、150 s-1升高,毛细管血浆粘度升高(P<0.05或P<0.01).丹参酮组各时间点毛细管血浆粘度、红细胞聚集率、细胞刚性指数、变形指数降低极其显着(P<0.01).

结论:丹参酮-ⅡA磺酸钠减轻脊髓缺血再灌注损伤可能是通过调控炎性因子NF-КB、VCAM-1的表达,降低全血粘度、毛细管血浆粘度、红细胞聚集和刚性指数、红细胞变形指数,从而有效改善血液流变性。
【关键词】脊髓缺血  脊髓损伤  血管细胞粘附分子-1  血液流变学
 
Effects of Tanshinone-ⅡA sulfonate on expression of Nuclear factor-kappaB,Vascular Cell Adhesion Molecule-1 and hemorrheology during spinal cord ischemia reperfusion injury
ABSTRACT  

Objective:To observe effects of Tanshinone-Ⅱ A sulfonate on expression of Nuclear factor-kappaB(NF-κB),Vascular Cell Adhesion Molecule-l (VCAM-1)and hemorrheology during spinal cord ischemia reperfusion injury,and explore the function and mechnism.

Methods:Fifty-four New Zealand rabbits (aged 3 months,weighted 2.0±0.2 kg) were randomly divided into 6 in sham group(lumbar artery were separated in operation,0.8 ml/kg saline were injected at 0.5 h before and after operation),24 in ischemia group( lumbar artery were clipped after seperation,and the same dose of saline),24 in Tanshinone group (lumbar artery were clipped after seperation,and the same dose of Tanshinone-ⅡA sulfonate) . Abdomincal aorta blood were drawed after treatment respectively at 0.5 h,1 h,4 h and 8 h,and tesetd whole blood viscosity[high cut (mpa.s)/150(l/s),middle cut (mpa.s)/60(l/s) and low cut (mpa.s)/10(l/s)],capillary plasma viscosity,red cell aggregation index,rigid index,deformation index and electrophoresis index. Spinal cord tissues were divided into two sections,one fixed in 4% paraformaldehyde,another stored in liquid nitrogen. Immunohistochemical method and ELISA were used to test change of content of NF-κB and VCAM-1.

Results:①The expression of NF-κB in Tanshinone group were lowest,and in ischemia group were highest. ②Compared with sham group,VCAM-1 in ischemia group at different time were obviously increased,especially at 0.5,1 and 4 h(P<0.01),and had meaning at 8 h(P<0.05). Compare between Tanshinone group and ischemia group,VCAM-1 at 0.5 h were obviously decreased(P<0.01),and had meaning at 1 h,4 h and 8 h(P<0.05).③There were no postive vasvular expression in sham group,and at 0.5 h in Tanshinone group and ischemia group. The highest postive vasvular expression in ischemia group were at 1 h,4 h and 8 h,and had significant meaning at 1 h and 4 h between ischemia group and Tanshinone group(P<0.05),and 8 h were obviously most. ④The whole blood viscosity in ischemia group at 10 s-1、60 s-1、150 s-1 were highest,and capillary viscosity increased(P<0.05 or P<0.01). While capillary viscosity,red cell aggregation index,figid index,deformation index in Tanshinone group decreased obviously(P<0.01).

Conclusion:Tanshinone-II A sulfonate can relieve spinal cord ischemia reperfusion injury by regulating expression of NF-KB,VCAM-1,decreasing whole blood viscosity,capillary plasma viscosity,red cell aggregation index,rigid index,and improve hemorhelogy.
KEY WORDS  Spinal cord ischemia  Spinal cord injuries  Vascular cell adhesion molecule-1  Hemorrheology
 
引用本文,请按以下格式著录参考文献:
中文格式:张俐,安国尧,张文光,陈凯.丹参酮-ⅡA磺酸钠对脊髓缺血再灌注损伤NF-κB、VCAM-1和血液流变性的影响[J].中国骨伤,2012,25(12):1016~1020
英文格式:ZHANG Li,AN Guo-yao,ZHANG Wen-guang,CHEN Kai.Effects of Tanshinone-ⅡA sulfonate on expression of Nuclear factor-kappaB,Vascular Cell Adhesion Molecule-1 and hemorrheology during spinal cord ischemia reperfusion injury[J].zhongguo gu shang / China J Orthop Trauma ,2012,25(12):1016~1020
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