摘要
目的 为了研究重组人睫状神经营养因子（rhCNTF）与神经生长因子（NGF）联合给药对糖尿病大鼠胃肠神经功能紊乱的作用。方法 采用链脲佐菌素（streptozocin，STZ）诱发Ⅰ型糖尿病大鼠所致胃肠神经功能紊乱模型，动物随机分为正常组、模型组、NGF(0.02 mg·kg-1，im)组、rhCNTF(0.1 mg·kg-1，im)组、NGF和rhCNTF联合用药组，连续给药85 d。观察各组大鼠血糖、胃肠慢波电位、小肠壁内神经蛋白含量、胃肠推进功能以及胃肠对乙酰胆碱（Ach）、阿托品敏感性。结果 NGF和rhCNTF联合用药和单独用药对糖尿病大鼠血糖均无明显降低作用，十二指肠对Ach、阿托品的敏感性也未见明显改变，但均可改善糖尿病大鼠胃肠慢波电位，提高胃肠推进功能，同时增加了胃肠壁内神经蛋白含量，联合用药效果优于单独给药。 结论 NGF与RhCNTF联合用药具有较好的抗糖尿病导致的胃肠神经功能紊乱作用，其机制可能与他们对内脏植物神经的神经营养和神经保护作用有关，且具有一定的协同作用。
Abstract
OBJECTIVE To investigate the combined effect of recombinant human ciliary neurotrophic factor (rhCNTF) and nerve growth factor (NGF) on gastrointestinal neurosis in diabetic rats. METHODS Diabetic rat models were created by STZ. Rats were randomly divided into normal group， model group， NGF group (0.02 mg·kg-1， im)， rRhCNTF group (0.1 mg·kg-1， im)， NGF+RhCNTF group(0.02 and 0.1 mg·kg-1， respectively， im). Rats were continuously administered for 85 d. The blood sugar， slow wave in stomach intestine， S100 in intestine， peristalsis， sensitivity to Ach and artropine in intestine were detected after administrating for 85 days. RESULTS The blood glucose was not changed compared with to the model group， and the response of jejunum to Ach and atropine was not changed too. The frequency of slow wave of jejunum the content of S100 and the functions of the intestine were improved. CONCLUSION The function of intestine in diabetes rat can be improved by administering rhCNTF， and the important mechanism is the nerve protective effects of rhCNTF.
关键词
神经生长因子 /
重组人睫状神经营养因子 /
糖尿病 /
胃肠功能 /
神经病变
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Key words
nerve growth factor /
recombinant human ciliary neurotrophic factor /
diabetes mellitus /
intestine function /
neuropathy
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刘庆山 张莉 李韶菁 杨志宏 崔箭 杜冠华.
NGF与CNTF联合治疗糖尿病大鼠胃肠神经病变的实验研究[J]. 中国药学杂志, 2010, 45(2): 111-114
LIU Qing-shn;ZHNG Li;LI Sho-jing;YNG Zhi-hong;CUI Jin;DU Gun-hu.
Combined Effect of rhCNTF and NGF on Intestine Function Neuropath in Diabetes Mellitus Rat[J]. Chinese Pharmaceutical Journal, 2010, 45(2): 111-114
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参考文献
［1］ DE BLOCK， DE LEEUW， PELCKMANS， et al.Current concepts in gastric motility in diabetes mellitus［J］.Curr Diabetes Rev， 2006， 2(1)：113-130.
［2］ MISHRA M K， KOLI P， BHOWMICK S， et al. Neuroprotection conferred by astrocytes is insufficient to protect animals from succumbing to Japanese encephalitis［J］. Neurochem Int， 2007，50(5)：764-773.
［3］ LIU Q S， WANG Q J， DU G H， et al. Recombinant human ciliary neurotrophic factor reduces weight partly by regulating nuclear respiratory factor 1 and mitochondrial transcription factor A［J］. Eur J Pharmacol， 2007，563(1-3)：77-82.
［4］ STEEINBERG G R， WATT M J， ERNST M， et al. CNTF Stimulates muscle glucose uptake by a pi3-kinase dependent pathway that is impaired with obesity［J］. Diabetes， 2009， 58(4)：829-839.
［5］ MA H P， ZHU Y F， SHAO Z Y. Protective effect of nerve regeneration factor on peripheral neuropathy of diabetic rats［J］. Chin J Clin Rehabilit（中国临床康复）， 2005， 9(29)：87-89.
［6］ HSIEH H L，SCHAFER B W， SASAKI N， et al. Expression analysis of S100 proteins and RAGE in human tumors using tissue microarrays［J］. Biochem Biophys Res Commun， 2003，307(2)：375-381.
［7］ MIOTKE J A， MACLENNAN A J， MEYER R L. Immunohistochemical localization of CNTFRalpha in adult mouse retina and optic nerve following intraorbital nerve crush： Evidence for the axonal loss of a trophic factor receptor after injury［J］. J Comp Neurol， 2007， 500(2)：384-400.
［8］ LIU Q S， GAO M， ZHU S Y， et al. The novel mechanism of recombinant human ciliary neurotrophic factor on the anti-diabetes activity［J］. Basic Clin Pharmacol Toxicol， 2007，101(2)：78-84.
［9］ LIU Q S， ZHU S Y， LI S J， et al. Effects of recombinant human ciliary neurotrophic factor on intestine function degenerating in diabetes mellitus rat model ［J］. Chin Pharm J（中国药学杂志）, 2008， 43(14)：1078-1081.
［10］ NICHOLLS K. Diabetic nephropathy——how might we prevent， retard， or cope with it［J］. Aust Fam Physician， 2005，34(11)：933-936.
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