CAJ | 학술논문

目的：芍药苷是一种潜在的神经保护药。文中探讨芍药苷对沙土鼠脑缺血再灌注（ cerebral ischemia／reperfusion， CI／R）损伤的保护作用及其作用机制。方法采用结扎双侧颈总动脉缺血10 min再灌注6 h，建立沙土鼠CI／R模型，随机数表法分为假手术组、模型组以及芍药苷5、10、20 mg／kg组，每组10只，术前3 d开始腹腔注射给药，1次／d，术前30 min给药1次。给药体积均为10 mL／kg，假手术组和模型组给予等体积等渗盐水。观察再灌注6 h内神经症状，计算卒中指数；放射免疫法测定内皮素和降钙素基因相关肽（ calcitonin gene-related peptide， CGRP）含量；黄嘌呤氧化酶法测定超氧化物歧化酶（ superoxide dis-mutase， SOD）活力，硫代巴比妥酸法测定丙二醛含量。结果芍药苷5、10、20mg ／kg组的卒中指数（14．8±3．6、12．3±2．0、12．7±1．4）较模型组（18．4±2．9）均明显降低（P＜0．05），而SOD活力[（99．30±9．71）、（106．85±15．13）、（110．25±14．90） nU／mgPro]较模型组[（86．54±10．22）nU／mg Pro]均显著升高（P＜0．05）；芍药苷10 mg／kg组、芍药苷20 mg／kg组脑组织丙二醛含量[（69．23±8．42）、（65．91±7．64）μmol／mgPro]较模型组[（94．76±10．30）μmol／mgPro]显著降低（P＜0．01）；芍药苷5、10、20 mg／kg组血浆内皮素水平[（24．06±5．37）、（19．62±5．60）、（21．08±4．64）ng／L]均比模型组[（30．52±7．13）ng／L]明显降低（P＜0．05），芍药苷对血浆CGRP水平则无明显影响。结论芍药苷预处理对CI／R损伤有保护作用，其原因与其减少脑组织自由基的产生、抑制脂质过氧化反应、抑制内源性神经肽内皮素的产生等有关。
목적：작약감시일충잠재적신경보호약。문중탐토작약감대사토서뇌결혈재관주（ cerebral ischemia／reperfusion， CI／R）손상적보호작용급기작용궤제。방법채용결찰쌍측경총동맥결혈10 min재관주6 h，건립사토서CI／R모형，수궤수표법분위가수술조、모형조이급작약감5、10、20 mg／kg조，매조10지，술전3 d개시복강주사급약，1차／d，술전30 min급약1차。급약체적균위10 mL／kg，가수술조화모형조급여등체적등삼염수。관찰재관주6 h내신경증상，계산졸중지수；방사면역법측정내피소화강개소기인상관태（ calcitonin gene-related peptide， CGRP）함량；황표령양화매법측정초양화물기화매（ superoxide dis-mutase， SOD）활력，류대파비타산법측정병이철함량。결과작약감5、10、20mg ／kg조적졸중지수（14．8±3．6、12．3±2．0、12．7±1．4）교모형조（18．4±2．9）균명현강저（P＜0．05），이SOD활력[（99．30±9．71）、（106．85±15．13）、（110．25±14．90） nU／mgPro]교모형조[（86．54±10．22）nU／mg Pro]균현저승고（P＜0．05）；작약감10 mg／kg조、작약감20 mg／kg조뇌조직병이철함량[（69．23±8．42）、（65．91±7．64）μmol／mgPro]교모형조[（94．76±10．30）μmol／mgPro]현저강저（P＜0．01）；작약감5、10、20 mg／kg조혈장내피소수평[（24．06±5．37）、（19．62±5．60）、（21．08±4．64）ng／L]균비모형조[（30．52±7．13）ng／L]명현강저（P＜0．05），작약감대혈장CGRP수평칙무명현영향。결론작약감예처리대CI／R손상유보호작용，기원인여기감소뇌조직자유기적산생、억제지질과양화반응、억제내원성신경태내피소적산생등유관。
Objective Paeoniflorin ( PAE) is a potential neuroprotective agent.In this study, we investigated the protective effect of PAE on cerebral ischemia/reperfusion ( CI/R) injury in gerbils and its underlying mechanisms. Methods The model of CI/R was established in 50 gerbils by bilateral common carotid occlusion for 10 min followed by 6-hour reperfusion.Then the animals were equally randomized into five groups:sham, model, 5 mg/kg PAE, 10 mg/kg PAE, and 20 mg/kg PAE.The latter three groups were treated with intraperitoneal injection of PAE once daily for 3 days before carotid occlusion, while the former two groups with saline only, all at 10 ml/kg.Stroke indexes were calculated during the reperfusion.The contents of endogenous neuropeptides, endothelin and calcitonin gene-related peptide ( CGRP) in the plasma were measured by radioimmunoassay.The levels of superoxide dismutase ( SOD) and malondialdehyde ( MDA) in the brain tissue homogenate were determined by the method of xanthine oxidase. Results The 5, 10, and 20 mg/kg PAE groups showed significantly decreased stroke index (14.8 ±3.6, 12.3 ±2.0, and 12.7 ±1.4) as compared with the model group (18.4 ±2.9) (P<0.05), but remarkably increased SOD activity ([99.30 ±9.71], [106.85 ± 15.13] , and [110.25 ±14.90] vs [86.54 ±10.22] nU/mgPro, P<0.05) .The MDA content was significantly lower in the 10 and 20 mg/kg PAE groups than in the model group ([69.23 ±8.42] and [65.91 ±7.64] vs [94.76 ±10.30] μmol/mgPro, P<0.01). The plasma endothelin level was markedly decreased in all the PAE groups in comparison with the model group ([24.06 ±5.37], [19.62 ±5.60] and [21.08 ±4.64] vs [30.52 ±7.13] ng/L, P<0.05). Conclusion The protective effect of PAE pretreatment in CI/R injury appears to be associated with the inhibition of the brain free radicals, lipid peroxidation and endothelin production.