高原大鼠脑组织Rho激酶活性变化及其与高原脑水肿关系的实验研究  

Change of Rho kinase activity in brain tissue in high altitude condition and its relationship with high altitude cerebral edema ： experiment with rats

作　　者：邓志宽[1] 郑健[1] 赵士福[1] 李黔宁[1] 刘勇[1] 程赛宇[1] 

机构地区：[1]第三军医大学附属新桥医院神经内科,重庆400037

出　　处：《中华医学杂志》2009年第13期923-926,共4页National Medical Journal of China

基　　金：第三军医大学校中青年基金（2003D090）

摘　　要：目的观察高原大鼠模型脑组织Rho激酶（ROCK）活性的变化，观察其与血脑屏障通透性及脑水肿的关系，探讨ROCK活性变化在高原脑水肿发生机制中的作用。方法30只Wistar大鼠随机分入正常对照组（HC）、高原组（HA）及法舒地尔干预组（Fasudil）；建立高原大鼠模型；法舒地尔干预组在建模前给予腹腔注射盐酸法舒地尔30mg／kg。造模24h后迅速断头取前脑，应用Western印迹法测定大鼠脑组织内ROCK活性、干湿重法测定脑组织含水百分率及应用荧光素钠透过率测定血脑屏障通透性。结果HA组大鼠脑组织ROCK活性、脑组织含水率及NaFI均明显高于HC组（ROCK活性从0．15±0．02上升到0．524±0．08，脑组织含水率从76．3％±1．1％增加到80．6％±1．8％，NaFI透过率从558rfu／mg±61 rfu／mg上升到732rfu／mg±54 rfu／mg，分别P〈0．001，P〈0．001，P〈0．01），Fasudil干预组大鼠脑组织ROCK活性、脑组织含水率及NaFI与HC组比较差异无统计学意义（均P〉0．05）。Fasudil干预组大鼠脑组织ROCK活性、脑组织含水率及NaFI明显低于HA组大鼠（ROCK活性从0．52±0．08下降到0．16±0．04，脑组织含水率从80．6％±1．8％下降到77．2％±1．5％，NaFI透过率从732 rfu／mg±54 rfu／mg下降到569 rfu／mg±43 rfu／mg，分别P〈0．001，P〈0．001，P〈0．01）。结论高原环境下脑组织ROCK显著激活，ROCK的异常激活可能是高原脑水肿形成的关键环节。Objective To observe the change of Rho kinase activity in brain tissue in the high altitude condition and its relationship with blood brain barrier permiability and high altitude cerebral edema （HACE） , and to explore the pathological mechanism of HACE. Methods 30 Wistar rats were divided randomly into 3 equal groups, high altitude （HA） group put in low pressure cabin mimicking high altitude of 7000 m for 24hr and then gradually exposed to higher pressure until the normal pressure, fasudil group undergoing intraperitoneal injection of fasudil hydrochloride 30 mg/kg, a Rho-associated coiled-coilcontaining protein kinase （ROCK） inhibitor, and then treated as the HA group, and normal control group （ HC group）. Five rats from each were decapitated with their brains taken out. The ratio of dry brain weight and wet brain weight was calculated. Western blotting was used to detect the expression of ROCK. Another 5 rats from each groups underwent injection of sodium fluorescein into the caudal vein and then the rats were decapitated to examine the natrium （sodium） fluorescence index （NaFI） of the central brain slice so as to observe the blood brain barrier permeability. Results The ROCK activity in brain tissue, ratio of dry and wet brain weight and NaFI of the HA group were significantly higher than those of the HC group （ all P 〈 0. 001 ）, and ROCK activity in brain tissue, ratio of dry and wet brain weight and NaFI of the fasudil group were all significantly lower than those of the HA group （ all P 〈 0. 001 ） and not significantly different from those of the HC group （ all P 〉 0.05）. Conclusions ROCK in brain tissue is activated in high altitude condition, which may play a key role in the development of HACE.

关 键 词：RHO激酶 高原脑水肿 法舒地尔 大鼠 

分 类 号：R686[医药卫生—骨科学]