中文摘要：

目的探讨嗜铬粒蛋白A（CGA）衍生多肽CGA47-66（CHR）对脓毒症小鼠血脑屏障通透性的影响。方法健康雄性C57BL／6小鼠120只，按随机数字表法分组，每组12只。72只用于观察脂多糖（LPS）诱导小鼠脑组织含水量和脑组织伊文思蓝（EB）含量的动态变化。另48只分为生理盐水对照组（NS组）、LPS诱导脓毒症模型组（LPS组）、低剂量CHR预处理组（CL＋LPS组）及高剂量CHR预处理组（CH＋LPS组）o腹腔注射10mg／kg、LPS0．1mL制备脓毒症小鼠模型；NS组注射等量生理盐水；CL＋LPS组和cH＋LPs组于注射LPS前10min分别腹腔注射CHR15．5ug／kg和77．5ug／kg。6h后经尾静脉注射2％EB4mL／kg，检测脑组织含水量和EB含量；采用荧光示踪法定性观察血脑屏障通透性变化；苏木素一伊红（HE）染色后观察脑组织病理学改变。结果注射LPS后随着时间的延长，脑组织含水量和EB含量均逐渐增加，脑组织含水量与对照组出现统计学差异的时间早于EB含量变化的时间（分别为3h和6h）。LPS组脑组织含水量及EB含量均较NS组明显升高[脑组织含水量：（79．77±0．62）％比（78．28±0．44）％，P〈0．01；EB含量（ug／g）：13．87±4．50比7．13±1．76，P〈0．05]；而两个CHR预处理组均可逆转LPS诱导的脑组织含水量和EB含量增高，以CH＋LPS组效果更加明显[脑组织含水量：（78．15±0．73）％比（79．77±0．62）％，EB（ug／g）：7．09±2．59比13．87±4．50，均P〈0．05]。EB荧光观察结果显示，NS组荧光信号仅存在于脑膜；LPS组脑实质中可见EB荧光广泛分布，说明EB渗漏较NS组明显；两个CHR预处理组脑实质中EB荧光减少，说明EB渗漏明显减少，且以高剂量组改善更为明显。HE染色显示，NS组脑血管结构清晰，周围间隙未见明显增大；LPS组脑组织结构疏松，小血管周围间隙明显增宽，水肿明显；两个CHR预处理组脑水肿较LPS

英文摘要：

Objective To explore the effect of chromofungin （CHR）, a chromogranin A （CGA） derived peptide CGA47-66, on hyper-permeability of blood brain barrier in septic mice. Methods 120 healthy male C57BL/6 mice were randomly divided into groups, with 12 mice in each group. Seventy-two mice were used for dynamic observation of the contents of water and Evan blue （EB） in brain tissue after being treated with lipopolysaccharide （LPS）. Another 48 mice were divided into normal saline control group （NS group）, LPS induced sepsis model group （LPS group）, low-dose CHR pretreatment group （CL＋LPS group）, and high-dose CHR pretreatment group （CH＋LPS group）. The septic model was reproduced by intraperitoneal injection of 10 mg/kg LPS 0.1 mL, and the mice in NS group was given equal volμme of normal saline. The mice in CL＋LPS group and CH＋LPS group were intraperitoneally injected with 15.5 p.g/kg and 77.5 p.g/kg CHR 10 minutes before LPS injection. Six hours after LPS injection, 4 mL/kg of 2% EB was injected via caudal vein, the contents of water and EB in brain tissue were determined, and EB immune fluorescence in brain tissue was determined to assess the changes in permeability of blood brain barrier. Brain pathology was observed with hematoxylin and eosin （HE） staining. Results With the extension of time after LPS injection, the contents of water and EB in brain tissue were gradually increased, and the time of difference with statistical significance appeared earlier when compared with that of control group in the contents of water than that in EB contents （3 hours and 6 hours, respectively）. The contents of water and EB in brain tissue in LPS group were significantly increased as compared with NS group [water content： （79.77＋0.62）% vs. （78.28＋0.44）%, P 〈 0.01; EB content （ug/g）： 13.87＋4.50 vs. 7.13＋1.76, P 〈 0.05]. CHR pretreatment with either of two dosages could reverse the increase in water and EB contents in brain tissue induced by LPS, and the effec