透明质酸合成酶1在脑出血后脑组织透明质酸含量及相对分子质量变化过程中的作用  

Role of Hyaluronan Synthase 1 in the Changes of Hyaluronan Content and Size Distribution after Intracerebral Hemorrhage in Mice

作　　者：丁宏岩[1] 姜家珍[2,3] 唐宇平[1] 董漪[1] 董强[1] 任惠民[1] 卓丽圣 木全弘治[3] 

机构地区：[1]复旦大学附属华山医院神经内科,200040 [2]复旦大学附属华山医院危重病科,200040 [3]日本爱知医科大学

出　　处：《中国临床神经科学》2013年第2期138-145,共8页Chinese Journal of Clinical Neurosciences

摘　　要：目的观察透明质酸合成酶1(HAS1)在脑出血后脑内透明质酸(HA)含量和相对分子质量变化过程中的作用。方法采用自体血注射法制作HAS1基因敲除小鼠和野生型C57BL/6J小鼠脑出血模型。分别分为出血后24 h组、出血后72 h组和对照组(不注自体血,余同),每组均n=6。提取出血侧半球脑组织的HA,经凝胶层析分离后用ELISA方法检测HA的总量和相对分子质量分布。Real time PCR方法观察HAS1、HAS2、HAS3和透明质酸分解酶(Hyal)mRNA表达水平的变化。通过对野生型C57BL/6J小鼠和HAS1基因敲除小鼠的比较,评价HAS1在此过程中的作用。结果脑出血后,①野生型C57BL/6J小鼠脑HA含量基本不变,仅在出血后72 h组呈轻微下降,但HA相对分子质量分布有显著变化,出血后24 h组呈现一过性的大分子HA的比例增加。②HAS1基因敲除小鼠脑内HA总量比野生型C57BL/6J小鼠减少1/4。出血后72 h组的HA总量明显下降,而且出血后24 h组的大分子HA比例不升反降,至出血后72 h后也未见恢复。③出血后,基因表达均随时间而增加,增幅大小顺序为HAS2>HAS3>HAS1,Hyal1>Hyal3>Hyal2。野生型C57BL/6J和HAS1基因敲除小鼠间只有HAS3的表达有差异。结论 HAS1基因敲除导致脑内HA总量减少1/4,脑出血后24 h HAS3基因表达代偿性增加,导致脑出血后脑内大分子HA含量下降。Aim To reveal the role ofhyaluronan synthase I（HAS1） in the changes ofhyaluronan （HA） content and size distribution after intracerebral hemorrhage（ICH） in mice. Methods ICH model was established by injecting autologous blood into right caudate nuclei. HA in the hemorrhagic hemispheres were extracted from the non- operated mice, 24 h post ICH, and 72 h post ICH groups （n=6 in each group） and then separated by gel filtration chromatography. HA amounts were measured by ELISA. The mRNA amounts of HAS 1, HAS2, HAS3 and hyaluronidase 1 （Hyall）, Hyal2, Hyal3 were measured by real-time PCR. The role of HAS 1 was evaluated by comparing the results from wild type C57BL/6J mice and HAS1 knockout mice. Results HA content did not change significantly after ICH in the wild type mice, though showing a slight decrease at 72 h post ICH. However, the size distribution of HA changed significantly, showing a transient increase in the percentage of high molecular weight HA at 24 h post ICH. In the absense of HAS1, the HA content decreased by 25.6%, and the decrease of HA content at 72 h post ICH was more significant than that in the wild type mice. In addition, the percentage of high molecular weight HA rather decreased at 24 h post ICH, and did not recovered at 72 h post ICH, in sharp contrast with that in the wild type mice. The gene expression of HAS1-3 and Hyall-3 increased along with time after ICH. The order by the extent of increment was HAS2〉HAS3〉HAS1 and Hyall〉 Hyal3〉 Hyal2. Only HAS3 expression may be higher in HAS1 group than WT（P=0.05）. Conclusion The absence of HAS1 resulted in 25.6% decreased of total HA content in brain, and induced a compensatory unregulation of HAS3 gene expression at 24 h post ICH, which finally brought about high molecular weight HA decreased after ICH.

关 键 词：脑出血 透明质酸 透明质酸合成酶1 透明质酸分解酶 相对分子质量 

分 类 号：R979.5[医药卫生—药品]