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不同给药方式下降钙素基因相关肽在蛛网膜下腔出血大鼠的组织分布

Tissue distribution of calcitonin gene-related peptide administered via different routes in rats with subarachnoid hemorrhage

摘要目的 探讨经鼻给药、经静脉给药降钙素基因相关肽(CGRP)在蛛网膜下腔出血(SAH)大鼠的组织分布.方法 采用枕大池两次注入新鲜自体动脉血的方法建立SAH大鼠模型,64只大鼠按随机数字表法分为4组:(1)A组(n=16):经鼻给予125I标记的CGRP(125I-CGRP)处理正常大鼠;(2)B组(n=16):经鼻给予125I-CGRP处理SAH模型大鼠;(3)C组(n=16):经股静脉给予125I-CGRP处理正常大鼠;(4)D组(n=16):经股静脉给予125I-CGRP处理SAH模型大鼠.采用放射性同位素示踪法比较处理30 min后各组大鼠CGRP的组织分布.结果 经鼻给予125I-CGRP后,正常大鼠和SAH模型大鼠各脑区、颈髓和脑脊液的CGRP浓度均显著高于经静脉给药,而血液、甲状腺、颈深淋巴结、肝和肺组织CGRP浓度均显著低于经静脉给药(均P<0.05).经鼻给药后以嗅球的CGRP浓度最高,其次为脑脊液和颈髓.结论 经鼻给药和经静脉给药CGRP具有组织分布差异性,在中枢神经系统的药物治疗上经鼻给药具有显著优势.

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abstractsObjective To investigate the tissue distribution of calcitonin gene-related peptide (CGRP) by nasal versus intravenous administrations in rats with subarachnoid hemorrhage (SAH).Methods The SAH rat model was established by injecting fresh autologous arterial blood into cisterna magna twice.Sixty-four rats were divided into 4 groups by random digit table:(1) group A (n=16):the normal rats were treated with 125I marked CGRP (125I-CGRP) by nasal administration;(2) group B (n=16):the SAH model rats were treated with 125I-CGRP by nasal administration;(3) group C (n=16):the normal rats were treated with 125I-CGRP via femoral vein;(4) group D (n=16):the SAH model rats were treated with 125I-CGRP via femoral vein.The tissue distribution of CGRP in rats of each group at 30 min after the treatment was compared by radioisotope tracing.Results The CGRP concentrations of brain regions,spinal cord,and cerebrospinal fluid (CSF) in normal rats and SAH model rats by nasal administration of 125I-CGRP were significantly higher than those by intravenous administration;whereas the CGRP concentrations of blood,thyroid,deep cervical lymph nodes,liver and lung tissues in normal rats and SAH model rats by nasal administration of 125I-CGRP were significantly lower than those by intravenous administration (all P<0.05).After nasal administration,the CGRP concentration in the olfactory bulb was the highest,followed by those in CSF and spinal cord.Conclusion Tissue distribution of CGRP differs between nasal administration and intravenous administration.Nasal administration of CGRP shows significant advantages in the medical treatment for disorders of the central nervous system.

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