转化生长因子β_1经鼻三叉神经通路入脑研究

Trigeminal nerve pathway to brain following intranasal administration of transforming growth factor beta 1

目的通过经鼻给予大鼠转化生长因子β1(TGF-β1)来探讨药物经鼻三叉神经通路入脑的可能性。方法将健康雄性SD大鼠19只,随机分为对照组(n=6)和经鼻给药(IN)0.5h组(n=3)、1h组(n=4)、2h组(n=3)、6h组(n=3),即在经鼻给予50μl(20μg)TGF-β1后0.5、1、2、6h处死动物;对照组为不给药大鼠。取各组大鼠动脉血以及小脑、中脑、脑桥、延髓、上颈髓组织和双侧三叉神经,采用ELISA法检测各样本内TGF-β1含量。结果与对照组(15.01±1.50pg/mg)相比,IN0.5、1、2、6h组大鼠三叉神经TGF-β1含量均显著提高(P<0.05),1h(75.46±12.50pg/mg)达高峰。IN1h组大鼠延髓TGF-β1含量为7.57±1.75pg/mg,与对照组(3.30±0.35pg/mg)相比显著提高(P<0.01),脑桥TGF-β1含量(5.92±0.92pg/mg)与对照组(3.41±0.24pg/mg)比较无统计学意义。各实验组大鼠小脑、中脑、上颈髓及血浆中TGF-β1的含量在给药前后均无显著改变。结论经鼻给予TGF-β1后药物可绕过血-脑脊液屏障快速进入三叉神经,并沿三叉神经通路逆行转运至延髓等中枢神经系统(CNS),此种给药途径为治疗三叉神经及CNS疾病提供了一条新的思路。

Objective To study whether intranasally administered transforming growth factor betal （TGF-β1） can reach central nervous system （CNS） through the trigeminal nerve pathway. Methods Nineteen healthy male SD rats were randomly assigned into control group （n=6） and administration （IN） 0. 5h group （n=3）, 1h group （n=4）, 2h group （n=3） and 6h group （n=3）. Rats in IN groups were given 50μl （20/Lg） recombinant human TGF-β1 （rhTGF-β1） intranasally and were sacrificed at 0. 5, 1, 2 or 6h after IN following blood sample collection. The cerebellum, midbrain, pon, medulla and trigeminal nerve were separated quickly and the concentration of TGF-β1, was analyzed by ELISA. Results Compared with the control group （15. 01±1. 50pg/mg）, TGF-β1 was significantly elevated in the trigeminal nerve in all the IN groups （P〈：0. 05）, attaining its greatest level at lh （75. 46± 12. 50pg/mg）. It was also found that TGF-β1 concentration in medulla raised significantly at h following intranasal delivery （7. 57±1.75pg/mg） compared with the control group （3. 30±0.35pg/mg） （P〈：0.01）. TGF-β1 level in the pon was also increased at h, but no statistical difference existed （5. 92±0. 92 vs 3.41±0. 24pg/mg, P〉0. 05）. TGF-β1 concentrations in plasma and other caudal CNS regions, such as cerebellum, midbrain and cervical spinal cord, were not significantly changed compared with that in control group. Condusion TGF-β1 is likely to be absorbed by the trigeminal nerve following intranasal administration, and is subsequently delivered to some brain regions through the trigeminal nerve pathway, which may provide a potential treatment strategy for trigeminal nerve and CNS disorders.