大鼠脑出血后活化星形胶质细胞EGFR-JAK1/STAT3表达及Genistein的抑制作用

EGFR-JAK1/STAT3 Expression in activated astrocytes after intracerebral hemorrhage and inhibition effect of genistein

目的探讨EGFR-JAK1/STAT3信号通路在大鼠脑出血后星形胶质细胞活化中的作用。方法 SD大鼠60只,随机分为ICH组、DMSO组、GST组,每组20只,Ⅶ型胶原酶注入苍白球进行脑出血造模。GST组在造模后每天腹腔注射Genistein溶液(50 mg/kg),DMSO组腹腔注射相同剂量DMSO溶液,一次/d。取术后1 d、7 d、14 d、28 d共4个时间点进行神经功能评分,各时间点每组随机取5只大鼠处死取脑,免疫组化检测EGFR、GFAP在星形胶质细胞中的表达变化,Western blot检测每各组p-JAK1、p-STAT3蛋白水平的表达。结果神经功能评分:GST组优于ICH组与DMSO组、ICH组与DMSO组比较差异无统计学意义(P>0.05);免疫组化显示脑出血后EGFR、GFAP表达增高,给予GST干预后,GFAP、EGFR表达显著少于ICH组及DMSO组,差异有统计学意义(P<0.05);7 d时p-JAK1/p-STAT3蛋白表达显著上升,予GST干预后,p-JAK1/p-STAT3蛋白水平较ICH组明显降低,差异有统计学意义(P<0.05),DMSO组EGFR、GFAP及p-JAK1/p-STAT3蛋白表达水平,与ICH组比较,差异无统计学意义(P<0.05)。结论脑出血所致星形胶质细胞活化与EGFR表达上调有关,抑制EGFR表达,可使pJAK1/p-STAT3蛋白表达水平下调,提示EGFR-JAK1/STAT3信号通路可能与脑出血后星形胶质细胞活化相关。

Objective Explore the effects of the EGFR-JAK1 / STAT3 signaling pathway in activation of astrocytes after rats with intracerebral hemorrhage in rats. Methods Sixty SD rats were randomized into 3 groups： ICH group、DSMO group、GST group. and every groups had 20 rats. Every groups rats were used to make cerebral hemorrhage model was mades by injecting VII collagenase into the caudate nucleus. The rats in GST groups were injected Genistein（ 50 mg / kg / d） once a day respectively until they were put to death. The rats in DSMO groups were injected with DMSO solution once a day respectively until they were put to death. In 1 d,7 d,14 d,28 d after the operation,all the rats＇ neurological function were graded. Five rats were randomly selected to sacrifice in each time point in each group. Meanwhile,immunohistochemistry was used to detect the expressions of GFAP and EGFR on astrocytes in the brain tissue,and westernblot Western blot was used to detect the expressions of p-JAK1 and p-STAT3. Results No significant differences between group DMSO and group ICH（ P 〉0. 05） were found in neurological function scores,While group GST is wass better than the former two groups（ P〈 0. 05）. Results of immunohistochemical indicated. The expression of GFAP and EGFR were increased after ICH. Compared with group DMSO and group ICH,in group GST,there was a statistical decline.（ P 〈0. 05）. In 7th after ICH,p-JAK1 and p-STAT3 protein expressions were increased,but in group GST p-JAK1 / p-STAT3 protein expressions were less than group DMSO and group ICH,which had significant differences（ P 〈0. 05）. The expression of GFAP、EGFR,p-JAK / p-STAT protein lerels levels were not affected by DMSO solution used for GST. Conclusion The expression of EGFR and p-JAK1 / pSTAT3 increased in astrocytes were activited activated after rats with intracerebral hemorrhage in rats. The expression of pJAK1 / p-STAT3 decreased after inhibiting the expression EGFR. EGFR-JAK1 / STAT3 signaling pathway may be associated with cerebral hemorrhage astrocyte activation.