脂肪乳剂对急性布比卡因中毒SD大鼠海马齿状回星形胶质细胞活化的影响

Effects of Lipid Emulsion on Astrocytes Activation in Hippocampal Dentate Gyrus of SD Rats with Acute Bupivacaine Poisoning

目的探索脂肪乳剂对急性布比卡因中毒SD大鼠海马齿状回星形胶质细胞活化的影响。方法选取SPF级雄性SD大鼠50只,采用随机数字表法将其分为5组,分别为对照组、脂肪乳剂组、布比卡因组、脂肪乳剂后处理组和脂肪乳剂预处理组。经尾静脉注射制备急性布比卡因中毒模型,模型制备成功6 h时后取脑组织,通过HE染色观察SD大鼠海马齿状回的病理学改变,进行组织病理学评分;免疫组化法检测海马齿状回中胶质纤维酸性蛋白(GFAP)、脑源性神经营养因子(BDNF)和巢蛋白(Nestin)的阳性表达。结果与对照组相比,布比卡因组、脂肪乳剂后处理组和脂肪乳剂预处理组的脑组织病理评分均升高(P均<0.01);与布比卡因组相比,脂肪乳剂后处理组和脂肪乳剂预处理组的脑组织病理损伤程度均减轻(P均<0.01);脂肪乳剂后处理组和脂肪乳剂预处理组差异无统计学意义(P>0.05)。与对照组相比,布比卡因组、脂肪乳剂后处理组和脂肪乳剂预处理组的大鼠脑组织中BDNF、GFAP和Nestin蛋白表达均升高(P均<0.01);与布比卡因组相比,脂肪乳剂后处理组和脂肪乳剂预处理组BDNF、GFAP和Nestin蛋白表达均降低(P均<0.01);脂肪乳剂后处理组和脂肪乳剂预处理组差异无统计学意义(P>0.05)。结论脂肪乳剂可以迅速逆转布比卡因所致SD大鼠的中枢神经毒性症状,其机制可能与星形胶质细胞活化抑制有关。

Objective To investigate the effect of lipid emulsion on astrocytes activation in hippocampal dentate gyrus of SD rats with acute bupivacaine poisoning.Methods Fifty SPF male SD rats were selected and divided into 5 groups by random number table,which were control group,lipid emulsion group,bupivacaine group,lipid emulsion post-treatment group and lipid emulsion pretreatment group.The acute bupivacaine poisoning model was prepared by tail vein injection.Six hours after the model was successfully prepared,the brain tissue was taken.HE staining was used to observe the pathological changes of the hippocampal dentate gyrus of SD rats,neuropathological score was used to evaluate qualitatively the neuronal damage.Immunohistochemistry was used to detect the distribution and expression of glial fibrillary acidic protein(GFAP),brain-derived neurotrophic factor(BDNF)and nestin(Nestin)in hippocampus tissue.Results Compared with the control group,the pathological scores of brain tissue in bupivacaine group,lipid emulsion postconditioning group and lipid emulsion pretreatment group were increased(P all<0.01);compared with bupivacaine group,the pathological damage of brain tissue in lipid emulsion postconditioning group and lipid emulsion pretreatment group were reduced(P all<0.01);there was no significant difference between lipid emulsion postconditioning group and lipid emulsion pretreatment group(P>0.05).Compared with the control group,the protein expressions of BDNF,GFAP and nestin in bupivacaine group,lipid emulsion postconditioning group and lipid emulsion pretreatment group were increased(P all<0.01);compared with bupivacaine group,the protein expressions of BDNF,GFAP and nestin in lipid emulsion postconditioning group and lipid emulsion pretreatment group were decreased(P all<0.01);the protein expressions of BDNF,GFAP and nestin in lipid emulsion postconditioning group and lipid emulsion pretreatment group were lower than those in bupivacaine group(P all<0.01)The difference was not statistically significant(P>0.05).Conclusion Lipid emulsion can rapidly reverse the symptoms of bupivacaine induced central neurotoxicity in SD rats,and the mechanism may be related to the inhibition of astrocyte activation.