CAJ | 학술논문

目的：探讨急性乌头碱中毒脑损伤机制及黄芩苷的干预作用。方法将SD大鼠200只按随机数字表法分为正常对照组、黄芩苷对照组、乌头碱中毒组、黄芩苷15 mg/kg干预组和30 mg/kg干预组，每组40只。采用尾静脉注射乌头碱20μg/kg复制乌头碱中毒模型。正常对照组和黄芩苷对照组分别经尾静脉注射生理盐水2 mL/kg和黄芩苷30 mL/kg；黄芩苷干预组于制模后2～3 min内注射黄芩苷15 mg/kg、30 mg/kg。观察各组大鼠给药后1、6、12、24 h各时间点脑组织病理学变化，谷氨酸（Glu）、天门冬氨酸（Asp）、γ-氨基丁酸（GABA）、甘氨酸（Gly）含量变化及神经元细胞凋亡情况。结果与正常对照组比较，乌头碱中毒组兴奋性氨基酸Glu、Asp含量及神经元凋亡数目显著升高；染毒后1 h大鼠脑皮质抑制性氨基酸GABA、Gly含量较正常对照组显著降低（均P＜0.05），6 h和12 h 明显升高，24 h后开始下降，但仍维持相对较高的水平。与乌头碱中毒组比较，15 mg/kg、30 mg/kg黄芩苷干预组给药后1 h Glu与Asp含量即明显降低〔Glu（μmol/L）：309.39±14.59、307.22±23.69比370.46±40.31，Asp（μmol/L）：143.43±8.36、129.12±4.86比222.97±6.26〕， GABA、Gly含量升高〔GABA（μmol/L）：55.91±4.76、59.61±13.11比32.05±2.20，Gly（μmol/L）：32.33±1.85、33.90±0.66比21.96±4.75〕，脑皮质凋亡数目显著降低（个/mm2：18.65±4.10、14.80±1.89比58.15±3.68，均P＜0.05）。光镜和电镜下可见，乌头碱中毒组于染毒后12 h脑皮质损伤最明显，15 mg/kg、30 mg/kg黄芩苷干预组脑皮质损伤较乌头碱中毒组有所减轻。结论大鼠急性乌头碱中毒所致的脑损伤可能与机体大脑皮质兴奋性递质Glu、Asp和抑制性递质GABA、Gly含量的失衡相关；黄岑苷能够降低兴奋性氨基酸含量提高抑制性氨基酸含量，从而减轻大鼠急性乌头碱中毒所致的脑损伤。目的：探討急性烏頭堿中毒腦損傷機製及黃芩苷的榦預作用。方法將SD大鼠200隻按隨機數字錶法分為正常對照組、黃芩苷對照組、烏頭堿中毒組、黃芩苷15 mg/kg榦預組和30 mg/kg榦預組，每組40隻。採用尾靜脈註射烏頭堿20μg/kg複製烏頭堿中毒模型。正常對照組和黃芩苷對照組分彆經尾靜脈註射生理鹽水2 mL/kg和黃芩苷30 mL/kg；黃芩苷榦預組于製模後2～3 min內註射黃芩苷15 mg/kg、30 mg/kg。觀察各組大鼠給藥後1、6、12、24 h各時間點腦組織病理學變化，穀氨痠（Glu）、天門鼕氨痠（Asp）、γ-氨基丁痠（GABA）、甘氨痠（Gly）含量變化及神經元細胞凋亡情況。結果與正常對照組比較，烏頭堿中毒組興奮性氨基痠Glu、Asp含量及神經元凋亡數目顯著升高；染毒後1 h大鼠腦皮質抑製性氨基痠GABA、Gly含量較正常對照組顯著降低（均P＜0.05），6 h和12 h 明顯升高，24 h後開始下降，但仍維持相對較高的水平。與烏頭堿中毒組比較，15 mg/kg、30 mg/kg黃芩苷榦預組給藥後1 h Glu與Asp含量即明顯降低〔Glu（μmol/L）：309.39±14.59、307.22±23.69比370.46±40.31，Asp（μmol/L）：143.43±8.36、129.12±4.86比222.97±6.26〕， GABA、Gly含量升高〔GABA（μmol/L）：55.91±4.76、59.61±13.11比32.05±2.20，Gly（μmol/L）：32.33±1.85、33.90±0.66比21.96±4.75〕，腦皮質凋亡數目顯著降低（箇/mm2：18.65±4.10、14.80±1.89比58.15±3.68，均P＜0.05）。光鏡和電鏡下可見，烏頭堿中毒組于染毒後12 h腦皮質損傷最明顯，15 mg/kg、30 mg/kg黃芩苷榦預組腦皮質損傷較烏頭堿中毒組有所減輕。結論大鼠急性烏頭堿中毒所緻的腦損傷可能與機體大腦皮質興奮性遞質Glu、Asp和抑製性遞質GABA、Gly含量的失衡相關；黃岑苷能夠降低興奮性氨基痠含量提高抑製性氨基痠含量，從而減輕大鼠急性烏頭堿中毒所緻的腦損傷。
목적：탐토급성오두감중독뇌손상궤제급황금감적간예작용。방법장SD대서200지안수궤수자표법분위정상대조조、황금감대조조、오두감중독조、황금감15 mg/kg간예조화30 mg/kg간예조，매조40지。채용미정맥주사오두감20μg/kg복제오두감중독모형。정상대조조화황금감대조조분별경미정맥주사생리염수2 mL/kg화황금감30 mL/kg；황금감간예조우제모후2～3 min내주사황금감15 mg/kg、30 mg/kg。관찰각조대서급약후1、6、12、24 h각시간점뇌조직병이학변화，곡안산（Glu）、천문동안산（Asp）、γ-안기정산（GABA）、감안산（Gly）함량변화급신경원세포조망정황。결과여정상대조조비교，오두감중독조흥강성안기산Glu、Asp함량급신경원조망수목현저승고；염독후1 h대서뇌피질억제성안기산GABA、Gly함량교정상대조조현저강저（균P＜0.05），6 h화12 h 명현승고，24 h후개시하강，단잉유지상대교고적수평。여오두감중독조비교，15 mg/kg、30 mg/kg황금감간예조급약후1 h Glu여Asp함량즉명현강저〔Glu（μmol/L）：309.39±14.59、307.22±23.69비370.46±40.31，Asp（μmol/L）：143.43±8.36、129.12±4.86비222.97±6.26〕， GABA、Gly함량승고〔GABA（μmol/L）：55.91±4.76、59.61±13.11비32.05±2.20，Gly（μmol/L）：32.33±1.85、33.90±0.66비21.96±4.75〕，뇌피질조망수목현저강저（개/mm2：18.65±4.10、14.80±1.89비58.15±3.68，균P＜0.05）。광경화전경하가견，오두감중독조우염독후12 h뇌피질손상최명현，15 mg/kg、30 mg/kg황금감간예조뇌피질손상교오두감중독조유소감경。결론대서급성오두감중독소치적뇌손상가능여궤체대뇌피질흥강성체질Glu、Asp화억제성체질GABA、Gly함량적실형상관；황잠감능구강저흥강성안기산함량제고억제성안기산함량，종이감경대서급성오두감중독소치적뇌손상。
Objective To investigate the interference effect of baicalin on acute brain injury induced by aconitine in rats and its mechanism. Methods A total of 200 Sprague-Dawley(SD)rats were randomly divided into five groups:normal control,baicalin control,aconitine poisoning,baicalin 15 mg/kg intervention and baicalin 30 mg/kg intervention groups(each,n=40). Aconitine(20μg/kg)was given via tail vein in aconitine poisoning group. The rats in the normal control group and baicalin control group were respectively injected with saline 2 mL/kg and baicalin 30 mg/kg via tail vein. The aconitine poisoning rats were given with baicalin at the dose of 15 mg/kg and 30 mg/kg respectively in the low and high dose baicalin intervention groups within 2-3 minutes after injection of aconitine. Rats in all groups in the study were anesthetized and sacrificed at 1,6,12,24 hours after various agents were respectively given in the groups,the rat cerebral cortex samples were collected,the histological changes in normal and baicalin control groups and pathological changes of the aconitine poisoning rats were observed,the levels of glutamate(Glu),aspartate(Asp),γ-aminobutyric acid(GABA),glycine(Gly)were detected and the apoptotic cells were determined at the above time points. Results Compared with the normal control group,the aconitine poisoning group had significantly higher levels of excitatory amino acids Glu and Asp and the number of apoptotic neurons. After exposure to aconitine for 1 hour, the levels of inhibitory amino acids of GABA and Gly were markedly decreased in the rat cortex in the poisoning group compared to the normal control group(both P<0.05),at 6 hours and 12 hours they were significantly increased and after 24 h,they began to decline,but still maintained at relatively high levels. Compared with the aconitine poisoning group, after baicalin intervention for 1 hour,in the 15 mg/kg and 30 mg/kg baicalin intervention groups,the levels of Glu and Asp were markedly decreased〔Glu(μmol/L):309.39±14.59,307.22±23.69 vs. 370.46±40.31,Asp(μmol/L):143.43±8.36,129.12±4.86 vs. 222.97±6.26〕,while the levels of GABA and Gly were increased〔GABA(μmol/L):55.91±4.76,59.61±13.11 vs. 32.05±2.20,Gly(μmol/L):32.33±1.85,33.90±0.66 vs. 21.96±4.75〕,and the number of neuronal apoptosis was obviously decreased(cell/mm2:18.65±4.10,14.80±1.89 vs. 58.15±3.68,both P<0.05). Under microscope and electron microscope,the pathological and ultrastructural changes indicated that the aconitine poisoning group had the most marked cerebral cortex damage at 12 hours after poisoning,while the two baicalin intervention groups showed milder damage than that in aconitine poisoning group. Conclusions The neural toxic effect of aconitine in rats may be related to the imbalance between the neurotransmitter contents of excitatory Glu. Asp and inhibitory GABA,Gly in the cerebral cortex. Baicalin can decrease the contents of excitatory amino acid and elevate the inhibitory amino acid,therefore it may ameliorate the cerebral injury of acute aconitine intoxication in rats.