脑络欣通方对大鼠脑缺血后纹状体中5-HT、DA、NE、5-HIAA的影响

目的研究脑络欣通方对大鼠脑缺血再灌注损伤的作用机制。方法雄性SD大鼠100只,随机分为假手术组、模型组、预处理组、治疗3 d组、治疗7 d组,每组20只。复制MCAO(脑中动脉栓塞)/R大鼠模型。治疗3 d组造模后连续给予脑络欣通方3 d、治疗7 d组造模后连续给予脑络欣通方7 d,预处理组造模前给予脑络欣通方药7 d,3组每天灌胃给药2次,8.54 m L/kg。假手术组及模型组予以等量生理盐水灌胃7 d。解剖大鼠并取出脑组织,分离纹状体。采用激光多普勒血流仪(LDF)测定梗死侧纹状体局部脑血流量(r CBF);采用TTC染色法检测大鼠脑梗死体积;采用实时荧光定量PCR技术(qRT-PCR)测定5-HT(5-羟色胺)mRNA、DA(多巴胺)mRNA、NE(去甲肾上腺素)mRNA、5-HIAA(5-羟吲哚乙酸)mRNA的表达含量。结果与假手术组比较,模型组发生明显缺血现象,脑血流量显著降低,脑梗死体积显著升高(P0.01),其纹状体中的5-HT mRNA、DA mRNA、NE mRNA、5-HIAA mRNA表达水平显著降低(P0.01);与模型组比较,脑络欣通方预处理组、治疗3 d、治疗7 d组脑血流量明显恢复,脑梗死体积显著下降(P0.01),纹状体中的5-HT mRNA、DA mRNA、NE mRNA、5-HIAA mRNA表达水平显著升高(P0.01)。结论脑络欣通方具有明显预防和治疗MCAO大鼠脑损伤的作用,通过增加MCAO/R大鼠的脑血流量,降低MCAO/R大鼠脑梗死体积,提高MCAO/R大鼠的纹状体组织中5-HT mRNA、DA mRNA、NE mRNA、5-HIAA mRNA单胺类递质的表达,从而起到抑制缺血后再灌注对大脑纹状体的损伤作用。

Effects of Naoluo Xintong decoction on mRNA expressions of 5-hydroxytryptamine,dopamine,norepinephrine and 5-hydroxyindoleace-tic acid in corpus striatum tissues of MCAO rats

Objective To study the mechanism of protective effect of Naoluo Xintong decoction (NLXTD),a traditional Chinese medicine compound,on cerebral ischemia-reperfusion injury in rats. Methods Altogether 100 male SD rats were randomly divided five groups(each n =20 ):sham-opera-ted group,model group,premedication group,three-day-medication group and seven-day-medication group.After modeling,three-day-medication group was administered intragastrically (i.g.)NLXTD for consecutive three days,and the seven-day-medication group for seven days at the dose of 8.54 g/kg daily twice.The premedication group was treated with NLXTD of 8.54 g/kg daily twice for consecutive seven days before modeling .The model group and sham-operated group were treated with the distill water for seven days.Regional cerebral blood flow (rCBF)of corpus striatum of the side of cerebral infarction was measured by using laser Doppler imager (LDF).Then all the rats were sacrificed and the corpus striatum were dissected out from brain.Infarct volume was determined by using 2,3,5-triphenyltetrazolium chlo-ride (TTC)staining,and the mRNA expressions of 5-hydroxytryptamine(5-HT),dopamine(DA),nor-epinephrine(NE)and 5-hydroxyindoleacetic acid (5-HIAA)in the corpus striatums were detected by qRT-PCR.Results Compared with the sham-operated group,the rats of the model group,with obvious cerebral ischemia,suffered more cerebral infarction volume(P <0.01),and the levels of mRNA expres-sion of 5-HT,DA,NE and 5-HIAA in corpus striatum significantly decreased(P <0.01).Compared with the model group,the cerebral infarction volume of premedication group,three-and seven-day-medica-tion group dramatically decreased by increasing the cerebral blood flow(P <0.01);the mRNA expres-sions of 5-HT,DA,NE and 5-HIAA increased significantly(P <0.01 ).Conclusion NLXTD could prevent and cure cerebral injury of MCAO rats by increasing the cerebral blood flow and decreasing the cerebral infarction volume to increase the mRNA expressions of monoamine transmitters of 5-HT,DA, NE and 5-HIAA of corpus striatum of rats.