摘要
目的探讨刺五加总黄酮(TFAS)对新生缺血缺氧性脑损伤(HIBD)大鼠脑组织的保护作用。方法用结扎左侧颈总动脉法建立新生HIBD大鼠模型,并随机分为模型组和实验组,每组10只;另取10只新生大鼠只分离左侧颈总动脉,但不结扎颈作为假手术组。假手术组和模型组均给予腹腔注射0.9%NaCl 0.5 mL,qd;实验组给予腹腔注射5 mg·mL^-1TFAS溶液0.5 mL,qd。3组大鼠均连续用药7 d。用酶联免疫吸附实验法检测血清中肿瘤坏死因子-α(TNF-α)、神经生长因子(NGF)和脑源性神经营养因子(BDNF)水平,用实时荧光定量聚合酶链反应法和免疫组织荧光法分别检测脑组织中组蛋白去乙酰化酶1(HDAC1)和K^+-Cl^-共转运体2(KCC2)mRNA及蛋白的表达水平。结果实验组、假手术组和模型组的TNF-α分别为(67.04±5.12),(30.12±4.03)和(100.12±4.03)μg·L^-1,NGF分别为(16.43±2.56),(22.05±3.37)和(8.67±1.03)μg·L^-1,BDNF分别为(14.96±1.85),(20.67±2.46)和(6.59±1.15)μg·L^-1,HDAC1 mRNA表达水平分别为(1.21±0.19),(1.92±0.24)和(1.00±0.09),KCC2 mRNA表达水平分别为(0.73±0.12),(0.47±0.09)和(1.00±0.11),HDAC1蛋白表达水平分别为(0.91±0.17),(0.74±0.15)和(1.46±0.21),KCC2蛋白表达水平分别为(1.37±0.19),(1.53±0.24)和(0.82±0.13),实验组的上述指标与假手术组和模型组比较,差异均有统计学意义(均P<0.05);假手术组的上述指标与模型组比较,差异均有统计学意义(均P<0.05)。结论TFAS可明显抑制新生HIBD大鼠TNF-α的表达水平,提高NGF和BDNF的表达水平,从而达到保护HIBD大鼠脑组织的作用,其机制可能与调控HDAC1和KCC2 mRNA和蛋白表达有关。
Objective To explore the protective effects of total flavonoids of Acanthopanax senticosus(TFAS)on brain tissue of neonatal rats with hypoxic-ischemic brain damage(HIBD).Methods The neonatal HIBD model rats were established by ligaturing left common carotid artery,and the model rats were randomly divided into model and experimental groups with 10 rats per group.And another 10 rats were treated with non-ligation method as the sham-operation group.The sham-operation group and model group were given 0.9%NaCl 0.5 mL by intraperitoneal injection.The experimental group was given 5 mg·mL^-1 TFAS solution 0.5 mL by intraperitoneal injection.Three groups were treated for 7 days with once a day.The levels of serum tumor necrosis factor-α(TNF-α),nerve growth factor(NGF)and brain derived neurotrophic factor(BDNF)were detected by enzyme-linked immunosorbent assay.The mRNA and protein expressions of histone deacetylase 1(HDAC1)and K^+-Cl^-co-transporter 2(KCC2)were detected by reverse transcription-polymerase chain reaction and immunohistochemical fluorescence.Results The levels of TNF-αin experimental group,sham-operation group and model group were(67.04±5.12),(30.12±4.03)and(100.12±4.03)μg·L^-1,the levels of NGF were(16.43±2.56),(22.05±3.37)and(8.67±1.03)μg·L^-1,the levels of BDNF were(14.96±1.85),(20.67±2.46)and(6.59±1.15)μg·L^-1,,the levels of HDAC1 mRNA were(1.21±0.19),(1.92±0.24)and(1.00±0.09),the levels of KCC2 mRNA were(0.73±0.12),(0.47±0.09)and(1.00±0.11),the levels of HDAC1 proteins were(0.91±0.17),(0.74±0.15)and(1.46±0.21),the levels of KCC2 proteins were(1.37±0.19),(1.53±0.24)and(0.82±0.13),respectively.There were significant differences in the above-mentioned indexes between the experimental group and the sham-operation and model groups(all P<0.05),and between sham-operation group and model group(all P<0.05).Conclusion TFAS can significantly inhibit the expression of TNF-αand increase the expressions of NGF and BDNF in neonatal HIBD rats,thus protecting the brain tissue of HIBD rats
作者
王柯威
颜艾
WANG Ke-wei;YAN Ai(Medical College,Shaoxing University of Arts and Science,Shaoxing 312000,Zhejiang Province,China;Department of Neurosurgery,Huzhou Central Hospital,Huzhou 313003,Zhejiang Province,China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2020年第6期624-627,共4页
The Chinese Journal of Clinical Pharmacology
基金
浙江省医药卫生计划课题资助项目(2015KYB375)。
