心肌营养素-1基因治疗大鼠脑损伤后心肌营养素-1和caspase-3的表达变化  

Expression changes of cardiotrophin-1 and caspase-3 in rats undergone cardiotrophin-1 gene therapy after traumatic brain injury

作　　者：杨云华[1] 廖维宏[1] 伍亚民[1] 张正丰[1] 李栋平[2] 邓洵鼎[2] 秦培韬[2] 

机构地区：[1]第三军医大学附属大坪医院野战外科研究所第三研究室、创伤、烧伤与复合伤国家重点实验室,重庆400042 [2]成都军区昆明总医院神经外科

出　　处：《中华创伤杂志》2007年第8期565-569,共5页Chinese Journal of Trauma

摘　　要：目的 观察外源性心肌营养素-1（CT-1）基因被载体重组腺病毒（Adv）导入损伤大脑细胞后在细胞中表达的情况及其对凋亡基因半胱氨酸天冬氨酸特异性蛋白酶-3（caspase-3）表达的影响，了解CT-1对损伤大脑神经元的作用和机制。方法 建立大鼠创伤性脑损伤（TBI）模型，于损伤脑区局部注射Adv—CT-1，应用免疫组化技术检测伤后及治疗后CT-1和caspase-3基因的表达变化。结果 TBI后1，3，7d，大脑皮层和海马等损伤脑区CT-1基因表达轻度增加；伤后12h、1，3，7d，在大脑皮层和海马等损伤脑区caspase-3基因表达明显增加，1d达高峰，3—7d逐渐降低。Adv—CT-1转染损伤脑区治疗后12h-7d，大脑皮层和海马等损伤脑区CT—1表达明显增加，7d达高峰；治疗后12h～7d在大脑皮层和海马等损伤脑区caspase-3基因表达较损伤对照组明显减少。结论 TBI后CT-1基因表达轻度增加，可能是机体对脑损伤后的反馈性保护机制；伤后caspase-3基因表达增加，是创伤后神经细胞凋亡的内在原因。伤后Adv—CT—1转染治疗可使CT-1基因在受损大脑中表达增加，而CT-1可下调凋亡基因caspase-3的表达，这可能是CT—1保护损伤神经元、促进神经功能恢复的内在机制。Objective To observe the expression of cardiotrophin-1 （ CT-1 ） gene after it was transfected into the traumatic brain cells by recombinant adenovirus vector （ Adv ） and investigate effect of CT-1 on expression of caspase-3 so as to understand the mechanism of CT-1 ＇ s action on the injured brain neurons. Methods By using Allen＇ s method, a rat model of traumatic brain injury （TBI） was established. Adv-CT-1 was transfected locally into the traumatic brain. And the expressions of CT-1 and caspase-3 gene after TBI and gene therapy were detected by immunohistochemistry respectively. Results The results showed that the expression of CT-1 gene in the injured cerebral cortex and hippocampus was increased slightly at 1,3 and 7 days after TBI. The expression of caspase-3 was increased significantly at 12 hours, 1, 3, and 7 days after TBI, reached peak at day 1 and gradually decreased from day 3 to day 7. From 12 hours to 7 days after transfection of Adv-CT-1 into the injured brain, the expression of CT-1 was increased significantly and reached peak at day 7. However, the expression of caspase-3 was decreased significantly, compared with that of the injury control group. Conclusions The slight increase of expression of CT-1 following TBI suggests a feedback protective mechanism of the body. The increased expression of caspase-3 may contribute to nerve cell apoptosis after TBI. Transfection of Adv-CT-1 into the traumatic brain may increase the expression of CT-1, while CT-1 decreases the expression of caspase-3, which may be interior mechanism of CT-1 protecting the injured neurons and refecting their functions.

关 键 词：脑损伤 基因疗法 CASPASE类 心肌营养素-1 

分 类 号：R686[医药卫生—骨科学]