8-OH-DPAT对弥漫性脑损伤及合并二次脑损伤大鼠神经元凋亡的影响

Neural apoptosis effect of 8-OH-DPAT on diffuse brain injury and secondary brain injury in rats

目的探讨5-羟色胺1A(5-HT1A)受体激动剂8-OH-DPAT[8-羟基-2-(二丙基氨基)四氢萘]对弥漫性脑损伤(diffuse brain injury,DBI)及合并二次脑损伤(secondary brain injury,SBI)大鼠神经元凋亡的影响。方法 182只健康雄性大鼠(330±25)g,随机分为6组:空白对照组(A组,n=7),假手术组(B组,n=35),单纯DBI+NS对照组(C组,n=35),单纯DBI+8-OH-DPAT治疗组(D组,n=35),DBI合并SBI+NS对照组(E组,n=35),DBI合并SBI+8-OH-DPAT治疗组(F组,n=35);根据伤后取脑时间分为6、12、24、72、168h亚组,各亚组7只。模型做成后,腹腔注射8-OH-DPAT(0.5mg/kg)或等体积生理盐水(normal saline,NS)。到达规定时间点,HE染色观察前额皮层病理表现;免疫组化检测前额皮层脑组织bax、bcl-2及半胱氨酸天冬氨酸蛋白酶-3(Caspase-3)蛋白的表达;原位末端标记(TUNEL)法检测前额皮层凋亡细胞。结果 A、B组各指标阳性表现很弱,各指标没有明显的差异(P>0.05);C、D、E、F组各时间点各指标分别与A、B组比较有明显差异(P<0.05或P<0.01);C、D组之间及E、F组之间各时间点各指标比较也有明显的统计学意义(P<0.05或P<0.01)。结论 8-OH-DPAT对大鼠弥漫性脑损伤及合并二次脑损伤后的神经元凋亡具有抑制作用。

Objective To study the effect of 5-HT1A receptor agonist 8-hydroxy-2-（di-n-propylamino） tetralin（8-OH-DPAT） on neural cells apoptosis in rats with diffuse brain injury（DBI） and secondary brain injury （SBI） . Methods One hundred and eighty-two adult male Wister rats weighing 305-355g were randomly divided into six groups,A： normal control group,n = 7; B： sham-operated group; C： DBI ＋ normal saline; D： DBI ＋ 8-OHDPAT; E： DBI with SBI ＋ normal saline; F： DBI with SBI ＋ 8-OH-DPAT. According to the brain-removal time,every group was divided into 6,12,24,72,168 hours subgroups,each subgroup consisted of 7 rats（n = 35） . After the successful establishment of model,intraperitoneal injection of 8-OH-DPAT （0. 5mg / kg） or equal volume normal saline was applied. Hematoxylin-Eosin staining was used to observe the pathological findings of the prefrontal cortex; Bax, BCL-2 and Caspase-3 protein expressions were detected by immunohistochemical method; and TUNEL method was used to detect the prefrontal cortical cell apoptosis. Results There was no significant difference in the index between group A and B （P 0. 05） ; there was remarkable difference in the index between groups of C,D,E and F and groups of A,B （P 0. 05 or P 0. 01） . And obvious statistical significance was also observed between groups of C,D and groups of E,F（P 0. 05 or P 0. 01） . Conclusion 5-HT1A receptor agonist 8-OH-DPAT has an inhibition effect on the neural cells apoptosis in rats with diffuse brain injury and secondary brain injury.