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目的:研究莫诺苷透过局造型脑缺血再灌注大鼠血脑屏障的能力。方法:建立大鼠在体脑血分布模型,探讨神经保护剂莫诺苷在正常组大鼠、假手术组大鼠和局灶性脑缺血再灌注模型组大鼠的脑靶向分布。采用线栓法制作局灶性脑缺血再灌注大鼠模型。造模成功后,3组大鼠尾静脉滴注莫诺苷溶液,待血药浓度达到稳态(55 min)后,取血和左右脑组织,采用已经建立的生物基质中莫诺苷浓度测定的LC-MS/MS方法测定大鼠血浆与脑组织中的莫诺苷浓度,并计算血脑分配系数(lg BB)。结果:莫诺苷在局造型脑缺血大鼠左右脑的lg BB分别为(1.36±0.44)和(2.26±0.13),但正常组大鼠和假手术组大鼠的lg BB值较低,药物透过该两组大鼠血脑屏障的能力较差,局造性脑缺血再灌注模型组大鼠的lg BB值明显高于正常组大鼠和假手术组大鼠。结论:较正常组大鼠和假手术组大鼠,莫诺苷可以明显透过局灶性脑缺血再灌注模型大鼠的血脑屏障。
OBJECTIVE: To study the ability of morroniside to penetrate the blood-brain barrier of cerebral ischemia- reperfusion rats. Methods: The rat cerebral blood distribution model was established to investigate the brain targeting distribution of neuroprotective agent, nobiletin, in normal rats, sham-operation rats and focal cerebral ischemia-reperfusion rats. The rat model of focal cerebral ischemia / reperfusion was established by thread occlusion. After successful modeling, the rats in the three groups were drenched with the solution of morroniside into the caudal vein, and the blood and left and right brain tissues were taken until the plasma concentration reached the steady state (55 min). The concentration of morroniside in the established biological matrix was measured The LC-MS / MS method was used to determine the concentration of morroniside in rat plasma and brain tissue, and the blood-brain partition coefficient (lg BB) was calculated. RESULTS: Morroniside had a lg BB of (1.36 ± 0.44) and (2.26 ± 0.13) in left and right cerebral ischemia rats, respectively. However, the values of lg BB in normal rats and sham operation rats were lower, The ability of drug to penetrate the blood-brain barrier of the two groups of rats was poor. The lg BB value of rats in the model group with focal cerebral ischemia-reperfusion was significantly higher than that of the normal rats and sham-operated rats. CONCLUSION: Compared with normal rats and sham-operated rats, morroniside can obviously penetrate the blood-brain barrier of focal cerebral ischemia / reperfusion model rats.