米诺环素对大鼠脑出血后bFGF表达的影响

The expression of bFGF after intracerebral hemorrhage treated with minocycline in rats

目的研究米诺环素(MC)对实验性脑出血后碱性成纤维细胞生长因子(bFGF)表达的影响。方法选用雄性SD大鼠110只,随机分为ICH组(n=50)、MC组(n=50)及假手术组(n=10),ICH组、MC组随机分为1、2、4、7和14d5个亚组(n=5),假手术组以建模后4d为总体对照点(免疫组化法n=5,RT-PCR法n=5)。采用Ⅳ型胶原酶注射法建立脑出血模型,MC组6h后腹腔注射MC(首次剂量:造模后6h腹腔注射MC(Sigma)45mg/kg,此后每12小时给予MC 22.5mg/kg)。ICH对照组及假手术组腹腔注射同等量的生理盐水。免疫组化及RT-PCR法检测bFGF的表达。结果血肿周围脑组织中胞浆内呈现棕黄色为bFGF阳性细胞,bFGF在神经细胞和血管内皮细胞均有表达。在4天时达高峰,各时间点ICH对照组和MC治疗组相比有显著性差异(P<0.05)。bFGF mRNA的表达水平4d时达到最高,而MC在1、2、4及7d各时间点均能减少VEGF mRNA的表达。结论 MC可降低大鼠脑出血后bFGF表达。

Objectives To establish a rat model of ICH by IV collagenase injection into striatum of rat brain fol- lowed by delayed Minocycline （MC） injection into peritoneal cavity and study the expression of bFGF after ICH. Methods 110 male SD rats （200-250g） were randomly divided into ICH control group （n=50）, MC treatment group （n= 50） and sham group （n= 10, with 4 days after modeling as the general control point, n= 5 for immunohistochemistry and n= 5 for RT-PCR）. Then, ICH control group and MC treatment group were randomly subdivided into 5 subgroups （ld, 2d, 4d, 7d, 14d. n=5）. Immunohistochemistry was used to detect basic fibroblast growth factor （bFGF） at different time point after ICH. The mRNA level of bFGF was measured by RT-PCR. Results bFGF positive cells were stained as yellow brown and found in different cells around the hematoma. Apparent expression was detected at ld, peaked at 4d and de- creased gradually as time proceeded following ICH. The bFGF mRNA expression was upregulated and MC was able to depress the expression of bFGF mRNA. Conclusion The expression of bFGF increased around the hematoma can be down-regulated by MC, which might be due to secondary inflammatory reaction inhibition by MC following ICH.