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Korean J Anat. 1998 Aug;31(4):565-580. Korean. Original Article.
Park KA , Park SH , Baik EJ , Lee WT .

Recently, it has been postulated that diabetic autonomic neuropathy is caused by reduction in availability of nerve growth factor (NGF) in enteric nervous system. This experiments were performed to determine the changes of the distribution of enteric neuropeptide by diabetes and these changes could be prevented by administration of NGF. Sprague Dawley rats (200~250gm) were made diabetic by a single intraperitoneal injection of streptozotocin 65 mg/kg in saline. Recombinant human NGF (Sigma, Co., Ltd.) were administered at a dose of 500ng/kg subcutaneously every day for consecutive 4 weeks after streptozotocin administration. After 4 weeks, rats were anesthetized with ether and perfused with 4% paraformaldehyde. ileum was dissected and prepared by whole mount preparation method. Prepared segments were immunostained for substance p, calcitonin gene-related peptide, vasoactive intestinal peptide, and galanin by PAP technique. For the observation of the interstitial cells of Cajal, segments were immersed in Champy-Maillet solution for 2 days Results obtained were as follows: 1. In myenteric plexus of diabetic rats, substance P-like and VIP-like immunoreactivity were not changed compared with that of the control group. CGRP-like and galanin-like immunoreactivity were decreased in diabetic group and immunoreactive cells for CGRP and galanin were also decreased 18.1% (P<0.01) and 43.7% (P<0.01) respectively. 2. In NGF administerd diabetic group, immunoreactivity of substance p, VIP, galanin in myenteric plexus were slightly increased and immunoreactive cells for substancre p, VIP, galanin were almost the same as that of the control group. However, immunoreactive cells for CGRP of myenteric plexus were not changed by NGF. 3. In submucous plexus of diabetic rats, immunoreactivity of all four neuropeptides(substance p, CGRP, VIP, galanin) were decreased compared with that of the control group. Immunoreactive cells for substance p, CGRP, VIP, and galanin were also decreased in 38.8%, 77.6%, 33.0%, and 35.7%, respectively (P<0.01). 4. In NGF administered diabetic group, immunoreactivities of substance p, VIP and galanin in submucous plexus were increased and the immunoreactive cells were increased significantly compared to diabetic group. However, immunoreactive cells for CGRP of submucous plexus were not changed by NGF. 5. Interstitial cells of Cajal of diabetic group were decreased 7.4% ovoidal cells (A type) and 28.3% round cells (B type) In NGF administered group, the morphology and the number of ICC were not different to the control group. With the above results, it could be assumed that NGF prevent the damage of neurotransmitter and ICC in enteric nervous system.

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